Schizophrenia Prodrome Research Articles

How does studying schizotypal personality disorder inform us about the prodrome of schizophrenia?

An increasing emphasis in the schizophrenia literature has been on the prodromal phase of the illness. The study of schizophrenia spectrum illness, including schizotypal personality disorder, has added important insight into the etiology, neuropathology, and treatment of schizophrenia, which can facilitate early identification, intervention, and perhaps prevention of the illness. The heterogeneity of the schizophrenia spectrum makes its definition elusive at best. The primary aim of the Cognitive Assessment and Risk Evaluation Program at the authors' institution is to combine the current knowledge of clinical and demographic risk factors for schizophrenia with the rapidly emerging data on vulnerability markers, or endophenotypes, that are associated with schizophrenia. The use of brain-based vulnerability markers may help to identify neurobiologically and clinically meaningful subgroups within this heterogeneous population of individuals in the early stages of schizophrenia. Another important aim of the Cognitive Assessment and Risk Evaluation program is to thoroughly assess those individuals who have not converted to psychosis to understand potential protective factors, reduce the rate of false positives, and decrease disability. The current review details a strategy for researching the schizophrenia prodrome by using information gained from research in schizotypal personality disorder.

First psychosis prodrome: Rehabilitation and recovery.

This paper explores some of the literature and the personal experience of the author to establish the key feature of the prodrome in first psychosis schizophrenia, the loss of functioning the individual experiences. The emerging literature on the subject is seen to lack consensus, and be focused on the predictive value of prodrome symptoms, not on potential rehabilitation and recovery issues. Because prodrome symptoms are disabling, experienced during the transition from adolescent to adult, and of considerable duration, they are likely to have a profound effect on rehabilitation and recovery in treatment.

Pathways to schizophrenic psychosis: A LISREL-tested model of the unfolding of the schizophrenic prodrome

In this article a literature-based model (the Schizotypic Syndrome Questionnaire [SSQ] model) is presented that gives a description of the temporal unfolding of the schizophrenic prodrome. As a guiding principle for the selection of the symptoms in the model, the hypothesis was held that the main prodromal features determine each other in terms of cause and effect. Furthermore, the developmental pathways between the symptoms were not allowed to be in conflict with the usual observation that negative symptoms precede psychotic-like ones nor--at least in broad outline--with J.P. Docherty, D.P. van Kammen, S.G. Siris, and S.R. Marder's (1978) description of the various onset stages in the development of a schizophrenic psychosis. For the definitive version of the SSQ model, 12 symptoms were selected (e.g., affective flattening, suspicion, and delusional thinking). After specifying the paths to be estimated, the model was examined in two randomly drawn samples from a total community-based sample of 771 normal subjects and in the total sample itself, in each case resulting in adequate fit values. Moreover, all postulated pathways were found to be significantly different from zero. The use of a normal sample was based on the continuum hypothesis. Given the present-day discussions concerning the tenability of the schizophrenia concept, the model's implications with respect to that issue are particularly emphasized. Furthermore, the concept of the schizophrenia prodrome itself is critically discussed.

The Use of Pharmacotherapy in the Prodrome of Schizophrenia

In treating schizophrenia there has been a shift in focus, with more attention being paid to early intervention based on the notion that effective treatment at this point can improve outcome. Most of this work has centred on pharmacotherapeutic interventions during the first psychotic break. More recently, attention has turned to the potential value of intervening even earlier, that is during the so-called "prodrome" that has been identified as predating the first psychotic break by as much as 4-5 years. We now have a limited number of published reports addressing this topic and these are reviewed here.

Chronic subdural hemorrhage in a patient with suspected schizophrenia prodrome

A patient showing "prodromal symptoms" of suspected psychosis was referred to our clinic specialized in early recognition of schizophrenia where an MRI brain scan showed a chronic subdural hemorrhage. Based on this case, it will be shown that organic brain disease, in addition to incipient schizophrenia, needs to be considered in patients with marked personality changes, social withdrawal, aggressiveness, and suspiciousness. Diagnosis of the first episode and prodromal stage of schizophrenia should include-apart from the case history as well as the psychopathological and physiological findings-certain obligatory medical examinations (EEG, cCT, or MRI) in order to identify possible organic causes and avoid misdiagnoses.

Anorectic symptomatology as a prodrome of schizophrenia: four case reports

AbstractWe describe four patients who originally presented with a diagnosis of adolescent anorexia nervosa and were subsequently diagnosed with schizophrenia. Overt positive symptoms of schizophrenia emerged during the course of treatment for the eating disorder. Symptoms such as social withdrawal and reduced work or academic performance, which had previously been attributed to the eating disorder, we considered to be negative symptoms of schizophrenia. We hypothesize that anorectic symptomatology may have represented prodromal features of schizophrenia in these patients. The clinical implications are discussed. Copyright © 2004 John Wiley & Sons, Ltd and Eating Disorders Association.

P50 sensory gating in adolescents from a pacific island isolate with elevated risk for schizophrenia

Background Gating or inhibition of the P50 auditory evoked potential is a heritable neurobiological trait that has shown strong potential to serve as an endophenotype for schizophrenia. P50 sensory gating deficits have been found repeatedly in schizophrenic patients and in their unaffected first-degree relatives. P50 sensory gating has not yet been studied in high-risk (HR) offspring nor in prodromal adolescents. Methods A paired-stimulus auditory event-related potential paradigm was used to examine P50 sensory gating in 44 genetically HR adolescent offspring and 43 clinically HR prodromal adolescents with the same low genetic liability as a comparison group of 39 normal adolescents. Results Auditory sensory gating, as measured by the P50 ratio, was impaired in both genetically HR offspring and also in the clinically HR prodromal adolescents with no close affected relatives. In the genetically HR group, abnormal P50 sensory gating was found only in offspring who met criteria for the schizophrenia prodrome. Conclusions Our findings suggest that P50 deficits are associated with the presence of prodromal symptoms, regardless of genetic risk. The results are consistent with the hypothesis that genetic liability in HR offspring increases risk for prodromal symptoms, and prodromal symptoms, in turn, increase risk for impaired sensory gating.

Neuropsychological status of subjects at high risk for a first episode of psychosis

Thirty-six subjects aged 16 years or older judged at risk for a first episode of psychosis within a North American multi-site study of the schizophrenia prodrome [McGlashan et al., Schizophr. Res. (2003); Miller et al., Schizophr. Res. (2003)] performed at levels intermediate to population norms and data reported for schizophrenia samples on a comprehensive neuropsychological exam. In the context of normal intelligence, this intermediate status suggests that, as a group, these subjects are not fully normal in neuropsychological functioning. Conversely, the finding that they do not show the levels of impairment commonly observed in schizophrenia, including within the first episode, suggests that prodromal interventions might conceivably prevent, delay, or lessen the severity of declines associated with first psychotic episodes.

Diagnosis and symptom assessment in the schizophrenia prodrome

The key characteristic of a traumatic event as defined by the Diagnostic and Mental Manual of Mental Disorders (DSM) seems to be a threat to life. However, evidence suggests that other types of threats may play a role in the development of PTSD and other disorders such as social anxiety disorder (SAD). One such threat is social trauma, which involves humiliation and rejection in social situations. In this study, we explored whether there were differences in the frequency, type and severity of social trauma endured by individuals with a primary diagnosis of SAD (n = 60) compared to a clinical control group of individuals with a primary diagnosis of obsessive compulsive disorder (OCD, n = 19) and a control group of individuals with no psychiatric disorders (n = 60). The results showed that most participants in this study had experienced social trauma. There were no clear differences in the types of experiences between the groups. However, one third of participants in the SAD group (but none in the other groups) met criteria for PTSD or suffered from clinically significant PTSD symptoms in response to their most significant social trauma. This group of SAD patients described more severe social trauma than other participants. This line of research could have implications for theoretical models of both PTSD and SAD, and for the treatment of individuals with SAD suffering from PTSD after social trauma.

The onset of psychotic disorder: A loose linkage model

The ability to detect individuals at high risk for developing schizophrenia before they express the disease will lead to targeted early intervention. It has been proposed that subjects at risk share a core deficit with people who already have schizophrenia. This includes cognitive impairment, affective symptoms, social isolation and decline in social functioning. In a sample of 104 help-seeking patients from a specialised outpatient clinic we investigated how well two different sets of criteria define the at-risk group and capture this core deficit. One set of criteria is the well-established ultra high-risk model of McGlashan et al. [McGlashan 2001 (SIPS) McGlashan, T. H., Miller, T. J., Woods, S. W., et al. (2001) Structured Interview for Prodromal Syndromes (Version 3.0, unpublished manuscript). New Haven, Connecticut: PRIME Research Clinic, Yale School of Medicine.]; the other criteria were those defined by Cornblatt et al. [Cornblatt, B., Lencz, T., Smith, C.W., Correll, C.U., Auther, A., Nakayama, E., 2003. The schizophrenia prodrome revisited: a neurodevelopmental perspective. Schizophr. Bull. 29, 633–651.]. There was considerable overlap in the two sets of criteria. However, when the basic symptoms of Klosterkötter [Klosterkötter, J., Hellmich, M., Steinmeyer, E.M., Schultze-Lutter, F., 2001a. Diagnosing schizophrenia in the initial prodromal phase. Arch. Gen. Psychiatry, 58, 158–164.] were included in the McGlashan et al. model, a more narrow and homogeneous group was defined.

Overview of the First Annual Workshop on the Schizophrenia Prodrome.

The First Annual Workshop of the Schizophrenia Prodrome was held in New York City in April 2002. This workshop was organized to address many of the unique methodological issues and controversies facing researchers interested in early intervention and prevention. It brought together representatives of most of the prodromal research groups active at that time as well as a number of consultants. This report summarizes the five major topics discussed throughout the workshop: (1) vulnerability and risk factors, (2) developmental issues, (3) neuroimaging and cognition, (4) alternative prevention strategies, and (5) clinical trials. The outcome of this workshop included consensus on several research issues, recognition that continued discussion and research was needed on many others, the emergence of a spirit of collaboration and collegiality among participants, and the very enthusiastic generation of the articles that make up this special issue of the Schizophrenia Bulletin. Two additional results were the decision to hold similar workshops in the future and the formation of the International Prodromal Research Network to foster international multisite collaborations.

Editors' Introduction: New Frontiers in Prodromal Research

This special issue emerged indirectly from discussions that took place on a train ride from Bonn to Berlin after an international conference held in Germany in 2000. At that time, a handful of research programs had been started to investigate the period preceding the onset of full-blown psychosis in individuals displaying attenuated (i.e., subpsychotic intensity) positive symptoms. One of us (B.A.C.) was interested in starting a collaborative project with other prodromal researchers on that train. But after a lunch, a few beers, and a slight detour to look at castles, it became quite clear that many issues had to be resolved before an international, multisite collaboration on this topic would be feasible. For example, some consensus was needed on issues such as how to define risk, how to define the prodrome, and how to quantify prevention. Furthermore, because most prodromal projects were quite new, few had had time to publish their early findings, and communication among researchers about shared problems, experiences, and discoveries had been limited And so the idea of a small interactive working group to overcome some of these problems was born. The First Annual Workshop on the Schizophrenia Prodrome was held at the SoHo Grand Hotel in New York City from April 4 to 6, 2002. Made possible by an educational grant from Janssen Pharmaceutica Products, L.P., the workshop focused on methodological issues unique to the study of risk states. Initially, it was hoped that, if successful, the workshop might result in a short article that would announce the emergence of the prodromal research area and provide a rudimentary methodological framework for researchers seeking to establish new programs in this field. What emerged was three days of intense scientific discussion, a very definite spirit of collegiality, and enough new data and theory to justify an entire special issue. John Hsaio, the editor-in-chief of Schizophrenia Bulletin, recognized the potential contribution of such a volume, and Robert Heinssen, a major contributor to the workshop, agreed to serve along with Barbara Cornblatt as primary co-editors. Tyrone Cannon and Todd Lencz also agreed to join the editorial board of the special issue. It was apparent to all that the field of prodromal research was no longer in its infancy but was experiencing an exciting spurt of growth, with all of die accompanying growing pains. This special issue cannot solve all the problems that cropped up that day on the train, but we believe that it will provide a major push in the right direction. While most of the contributors to this issue participated in the 2002 workshop, there are also several invited articles and commentaries by researchers who were unable to attend. To maximize the potential impact of this issue on the field, the editors and authors agreed to an unusually stringent review process. Articles were sent to as many as four internationally recognized opinion leaders in the field of schizophrenia research, in addition to review by the editors themselves. Our thanks are extended not only to the authors, who returned very strong contributions with relatively short deadlines, but also to the reviewers, who provided extensive comments on even tighter deadlines. This meeting also led to the formation of the International Prodromal Research Network (TPRN), which is codirected by Barbara Comblatt and Tyrone Cannon. The goal of the network is to provide a forum for researchers to form collaborations and to pool resources and data in pursuing goals related to the prediction and prevention of schizophrenia and other forms of psychosis. IPRN activities are expected to generate a set of common assessment instruments and to pave the way for the multisite trials critical for amassing large samples, currently not available to any one site or study. The network will also coordinate future workshops and smaller working group meetings. The first of these was the Second Annual Workshop, held in Santa Monica, CA, from May 1 to 3, 2003, which was hosted by Tyrone Cannon and co-sponsored by Janssen Pharmaceutica Products, L.P., and by Garen and Shari Staglin. The Staglins have pledged ongoing support of the network through funds raised at the Music Festival for Mental Health, held annually at the Staglin Family Vineyard in Rutherford, CA. The sec-

Prodromal assessment with the structured interview for prodromal syndromes and the scale of prodromal symptoms: predictive validity, interrater reliability, and training to reliability.

As the number of studies related to the early identification of and intervention in the schizophrenia prodrome continues to grow, it becomes increasingly critical to develop methods to diagnose this new clinical entity with validity. Furthermore, given the low incidence of patients and the need for multisite collaboration, diagnostic and symptom severity reliability is also crucial. This article provides further data on these psychometric parameters for the prodromal assessment instruments developed by the Prevention through Risk Identification, Management, and Education (PRIME) prodromal research team at Yale University: the Structured Interview for Prodromal Syndromes and the Scale of Prodromal Symptoms. It also presents data suggesting that excellent interrater reliability can be established for diagnosis in a day-and-a-half-long training workshop.

The New York high risk project to the Hillside recognition and prevention (RAP) program.

The sudden interest in initiating treatment before the onset of psychosis (i.e., during the prodromal stage of schizophrenia) has failed to integrate the earlier work on prediction generated by more traditional high-risk studies. Genetic high-risk research has most typically focused on the long-term, prospective study of children of parents with schizophrenia. In this paper, it will be argued that high-risk research can make at least two major contributions to prevention programs. First, previous findings can guide identification of risk factors and provide clues about causality, thus highlighting which pre-morbid deficits should be treatment targets. For example, as discussed here, data from the New York High Risk Project points to impaired attention as a highly promising candidate risk factor, with a possible causal association with later-emerging social deficits. Second, the high-risk approach can provide a framework for establishing the predictive validity of prodromal clinical indicators and for understanding the nature of the schizophrenia prodrome. Preliminary findings from the Hillside Recognition and Prevention (RAP) program, integrating high-risk methodology with an early intervention strategy, indicate that the prodrome is a developmentally complex phase of schizophrenia. In particular, a cluster of early features-including cognitive, academic, and social impairments, along with odd/disorganized behaviors-appear to anticipate positive symptoms and may constitute a core risk profile. Preliminary RAP treatment findings also suggest that medications other than anti-psychotics may be effective for treating early prodromal symptoms, challenging the widely held hypothesis that anti-psychotics should always be the first line preventive treatment.

Duration of the initial prodrome and prediction of schizophrenia

Duration of the initial prodrome and prediction of schizophrenia

The initial prodrome of schizophrenia: A case report

The initial prodrome of schizophrenia: A case report

The schizophrenia prodrome: treatment and high-risk perspectives

Interest in the prodromal stage of schizophrenia—the stage directly preceding the onset of psychosis—has recently undergone a dramatic increase. To a great extent, this has resulted from the convergence of two very different research traditions. Many treatment researchers have moved from a concern with symptom control to an interest in prevention and view the prodrome as the optimal stage to begin intervention with anti-psychotics. High-risk researchers, who view the identification of accurate risk factors as necessarily preceding preventive programs, have begun to move from the premorbid to the prodromal phase as the most effective starting point. Thus, researchers in both traditions have targeted the schizophrenia prodrome as the most likely gateway to prevention. However, clashes between the two traditions in approaches, methodology and research goals have also led to considerable controversy. Such issues as how best to define the prodrome, what the actual risk for schizophrenia is among prodromal individuals, and what type of medication should be used remain largely unresolved. The Hillside Recognition and Prevention (RAP) Program has been designed to address many of these and related questions. Within a naturalistic treatment framework, the RAP program combines both high-risk and treatment research strategies. Preliminary findings from a 3-year RAP pilot study, for example, suggest that the prodrome is a developmentally complex phase of schizophrenia, that it consists of distinctly different subgroups and that novel anti-psychotics are clearly beneficial for some but not all individuals. Depending upon clinical characteristics and phase of the prodrome, anti-depressants also appear highly effective.

Treatment of the schizophrenia prodrome: is it presently ethical?

Although the devastating consequences of schizophrenia have long been known, interest in preventive intervention has only recently emerged. The shift in focus toward early treatment has been encouraged by findings suggesting that the longer psychosis remains untreated, the poorer the prognosis, and by the recent introduction of novel antipsychotic medications with a more benign side effect profile than conventional neuroleptics. In this paper, we argue that interest in prevention has outpaced the necessary scientific and ethical underpinnings for clinical trials involving the schizophrenia prodrome. Specifically, we maintain that the prodromal phase of schizophrenia is, at present, essentially a retrospective construct and that, as a result, the defining signs and symptoms currently in use must be validated in naturalistic, longitudinal studies. In particular, it is essential to establish solid base rates for schizophrenia in prodromal individuals before early treatment can be effectively evaluated. Additional ethical/scientific issues discussed include: (1) the need for an exit strategy (i.e. the determination of when to discontinue treatment in an individual who does not develop schizophrenia), (2) the advisability of pharmacological interventions that specifically target neurocognitive deficits, and (3) the possibility that antidepressant medications may be as effective or more effective, with fewer side effects, than antipsychotic medication for prodromal individuals.

The schizophrenia prodrome: promise for prevention

Converging theoretical, psychopharmacological, neurodevelopmental advances have led to increasing interest in preventive intervention in schizophrenia. In particular, evidence suggests that early treatment is associated with a better prognosis. Furthermore, based on the reported reduction in severe side effects, the new novel antipsychotics potentially provide the tools for early intervention. Nevertheless, initiation of intervention during the prodrome has become controversial because of such unresolved issues as: (i) how to accurately identify susceptible individuals who are in true need of preventive intervention; (ii) at what developmental point in the prodrome medication should be initiated; (iii) how long medication should be continued; and (iv) what medication is optimal for each phase of the prodrome. By adopting a naturalistic, prospective research strategy, the Recognition and Prevention (RAP) program now underway in New York has been designed to address these and other important questions involved in prodromal research and treatment.

The Timing of Neurodevelopmental Abnormality in Schizophrenia: An Integrative Review of the Neuroimaging Literature

In this paper we will review recent neuroimaging research in schizophrenia, with an aim to critically evaluate several recent proposals concerning the nature and the timing of the neuroanatomic abnormalities underlying the disorder. Specifically, enlargement of cerebrospinal fluid spaces, deficits in cortical gray matter, and reduced volume of mesiotemporal structures have all been reported in patients in the first episode of schizophrenia, their first-degree relatives, and individuals with schizotypal personality disorder, supporting the possibility that these abnormalities reflect a genetically mediated neurodevelopmental disorder. These findings from the empirical literature will be synthesized from the perspective of dual cytoarchitectonic trends theory of neurodevelopment, as well as in relation to current conceptions of the schizophrenia prodrome. We believe that the evidence shows that sufficient groundwork has been laid to begin longitudinal neuroimaging studies of adolescents at clinical risk for schizophrenia, in order to more definitively determine the pathophysiology of the disorder. Such information could have significant implications in terms of understanding the prediction, treatment, and ultimately the prevention of schizophrenia.