Other articles by Diana O. Perkins on PubMed

• Predictors of Noncompliance in Patients with Schizophrenia The Journal of Clinical Psychiatry. Dec, 2002  |   Pubmed ID: 12523871 Around 50% of patients with schizophrenia do not fully comply with treatment, and noncompliance is linked to relapse, rehospitalization, poor outcome, and high economic costs. The health belief model views noncompliance as a decision made by the patient, arrived at after weighing the perceived risks and benefits of treatment.
• Implications for the Neural Basis of Social Cognition for the Study of Schizophrenia The American Journal of Psychiatry. May, 2003  |   Pubmed ID: 12727681 The study of social cognition in schizophrenia has received growing attention in recent years. At the same time, a large body of work has explored the neural basis of social cognition in both nonclinical and clinical groups, other than those with schizophrenia. The gap between these two literatures is considerable and may slow progress in creating a comprehensive social cognitive model of schizophrenia. This article attempts to bridge this gap by discussing how the neural basis of social cognition may inform future clinical research in schizophrenia.
• Assessing Clinical and Functional Outcomes in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia Trial Schizophrenia Bulletin. 2003  |   Pubmed ID: 12908659 Schizophrenia is a symptomatically heterogeneous disorder characterized by the presence of positive and negative symptoms, and variable impairment in community functioning. Given the diversity of symptom presentations and functioning associated with schizophrenia, one of the key challenges facing the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial was the selection of efficient assessment measures appropriate to a community-based effectiveness trial. This article describes the rationale for the measurement approach adopted for the trial, provides a brief overview of the selected measures, and describes the process of training assessment raters for a large and geographically dispersed study group.
• Randomized Trial of Olanzapine Versus Placebo in the Symptomatic Acute Treatment of the Schizophrenic Prodrome Biological Psychiatry. Aug, 2003  |   Pubmed ID: 12915290 The prodromal phase of schizophrenic disorders has been described prospectively. The present study aimed to determine the short-term efficacy and safety of olanzapine treatment of prodromal symptoms compared with placebo.
• Pharmacological Management of First-episode Schizophrenia and Related Nonaffective Psychoses Drugs. 2003  |   Pubmed ID: 14524730 Schizophrenia is a severe mental illness characterised by abnormalities of thought and perception that affects 1-2% of the population. Patients who experience a first episode of schizophrenia should be treated early and optimally with antipsychotic agents to lessen the morbidity of the initial episode and possibly improve the course of the illness. Positive psychotic symptoms remit in the majority of patients who are treated with adequate trials of antipsychotic medications, but most relapse within 1 year. Non-adherence is strongly related to the likelihood of recurrence of symptoms. Innovative programmes that integrate early intervention, psychosocial treatments and atypical antipsychotic pharmacotherapy show promise in improving outcomes. The available research supports the use of antipsychotic medications early in the first-episode of schizophrenia and for at least 1 year after remission of positive symptoms. Antidepressants, benzodiazepines and mood stabilisers have roles in the acute and maintenance phases of treatment for some patients. Atypical antipsychotics represent a great advance in the treatment of first-episode schizophrenia with strong evidence for greater tolerability with equal or better therapeutic efficacy. Future research will further define their roles in treatment and hopefully identify targets for prevention of first-episode schizophrenia.
• Prodromal Assessment with the Structured Interview for Prodromal Syndromes and the Scale of Prodromal Symptoms: Predictive Validity, Interrater Reliability, and Training to Reliability Schizophrenia Bulletin. 2003  |   Pubmed ID: 14989408 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.
• Practice Guideline for the Treatment of Patients with Schizophrenia, Second Edition The American Journal of Psychiatry. Feb, 2004  |   Pubmed ID: 15000267
• Brief Evaluation of Medication Influences and Beliefs: Development and Testing of a Brief Scale for Medication Adherence Journal of Clinical Psychopharmacology. Aug, 2004  |   Pubmed ID: 15232332 The purpose of this study was to develop and test a brief scale (Brief Evaluation of Medication Influences and Beliefs [BEMIB]) designed to identify patients who are more likely to be nonadherent to their antipsychotic medication.
• Evaluating and Treating the Prodromal Stage of Schizophrenia Current Psychiatry Reports. Aug, 2004  |   Pubmed ID: 15260945 Identification of a person in the prodromal stage of schizophrenia, before the onset of the first episode of psychosis, provides an opportunity for early, potentially preventative, interventions. Recent attempts to develop "at risk" or "prodromal syndrome" diagnostic criteria have proved to be successful at identifying individuals at high risk for psychosis. Preliminary investigations find that pharmacologic and psychotherapeutic interventions may reduce the risk of psychosis in "at risk" individuals, but until more is known, current treatment guidelines recommend close monitoring, therapeutic interventions that address identified problems, including supportive or cognitive therapies to reduce the functional consequences of the presenting symptoms, family interventions to reduce family distress and improve coping, and intervention with schools to decrease likelihood of school failure. Pharmacologic intervention targeting the prodromal symptoms is not recommended, given the uncertain risk-benefit ratio.
• Changes in Neuropsychological Functioning with Progression of HIV-1 Infection: Results of an 8-year Longitudinal Investigation AIDS and Behavior. Sep, 2004  |   Pubmed ID: 15475681 Despite the advent of more effective treatments for HIV-1 infection, cognitive impairment is still frequent and questions remain regarding which areas of impairment are more common in the different disease stages. This study investigated cognitive performance over an 8-year period of time in 59 HIV-1 seropositive (HIV-1+) men who were clinically asymptomatic at study entry, in comparison to a cohort of 55 HIV-1 seronegative (HIV-1-) men. Every 6 months we examined cognitive functioning in 5 domains-fine motor speed, attention, verbal memory, executive functioning, and speed of information processing. We found that patients with AIDS scored significantly worse on fine motor speed and speed of information processing than HIV-1- individuals and the HIV-1+ non-AIDS patients. In addition, the HIV-1+ non-AIDS patients performed more poorly than the HIV-1- group on speed of information processing. Depressive symptoms were also associated with diminished performance on measures of attention, executive functioning, and speed of information processing. Further research is needed to examine the effects of disease stage and depression on cognitive impairment in the era of new HIV treatments.
• Effect of Olanzapine on Body Composition and Energy Expenditure in Adults with First-episode Psychosis The American Journal of Psychiatry. Jan, 2005  |   Pubmed ID: 15625209 Weight gain is a commonly observed adverse effect of atypical antipsychotic medications, but associated changes in energy balance and body composition are not well defined. The authors report here the effect of olanzapine on body weight, body composition, resting energy expenditure, and substrate oxidation as well as leptin, insulin, glucose, and lipid levels in a group of outpatient volunteers with first-episode psychosis.
• Imaging Frontostriatal Function in Ultra-high-risk, Early, and Chronic Schizophrenia During Executive Processing Archives of General Psychiatry. Mar, 2005  |   Pubmed ID: 15753238 Individuals experiencing prodromal symptoms of schizophrenia (ultra-high-risk group) demonstrate impaired performance on tasks of executive function, attention, and working memory. The neurobiological underpinnings of such executive deficits in ultra-high-risk individuals remains unclear.
• Double-blind, Placebo-controlled Investigation of Amantadine for Weight Loss in Subjects Who Gained Weight with Olanzapine The American Journal of Psychiatry. Sep, 2005  |   Pubmed ID: 16135638 This study sought to determine if amantadine affects weight gain in psychiatric patients taking olanzapine.
• Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia The New England Journal of Medicine. Sep, 2005  |   Pubmed ID: 16172203 The relative effectiveness of second-generation (atypical) antipsychotic drugs as compared with that of older agents has been incompletely addressed, though newer agents are currently used far more commonly. We compared a first-generation antipsychotic, perphenazine, with several newer drugs in a double-blind study.
• Relationship Between Duration of Untreated Psychosis and Outcome in First-episode Schizophrenia: a Critical Review and Meta-analysis The American Journal of Psychiatry. Oct, 2005  |   Pubmed ID: 16199825 The duration of untreated psychosis may influence response to treatment, reflecting a potentially malleable progressive pathological process. The authors reviewed the literature on the association of duration of untreated psychosis with symptom severity at first treatment contact and with treatment outcomes and conducted a meta-analysis examining these relationships.
• Folded RNA from an Intron of One Gene Might Inhibit Expression of a Counteracting Gene In Silico Biology. 2005  |   Pubmed ID: 16268785 Homeostatic maintenance of mRNA levels including prompt availability of mRNAs for translation in response to changing protein demands might be partly enabled by a system of combinatorial controls involving noncoding RNA blocking agents. This article proposes a specific version of that control mechanism, namely, a double-stranded RNA folding from transcription of an intron of one gene might and leading to an agent that inhibits mRNA of a counteracting gene. Thus transcription of the first gene would automatically repress translation of the second. On the basis of a bioinformatics search, we suggest a possible example, namely, that pro-apoptosis gene PAR4 might inhibit anti-apoptosis gene XIAP. Part of an intron from PAR4 folds to form a large, stable hairpin, and reverse complement of the hairpin stem (with approximately 280 nucleotides) matches a sub-sequence of an exon in XIAP. This would be part of an efficient system to drive initiated apoptosis to its conclusion. Figuratively speaking, it replaces two control knobs with one. Since repeats, some with many thousands of copies, occur throughout the genome with complex distributions, care must be taken before asserting that the presence of any repeat in any gene is significant. Our apoptosis example involves repeats, so experimental verification is needed and planned. However, if it is found that the noncoding RNA by-product of one gene folds into a hairpin that is processed into an agent that inhibits a counteracting gene, then the same type of control unit might be found extensively among counteracting families of genes of many types.
• Course and Predictors of Weight Gain in People with First-episode Psychosis Treated with Olanzapine or Haloperidol The British Journal of Psychiatry : the Journal of Mental Science. Dec, 2005  |   Pubmed ID: 16319406 Substantial weight gain is common with many atypical antipsychotics.
• Psychosocial Treatment for First-episode Psychosis: a Research Update The American Journal of Psychiatry. Dec, 2005  |   Pubmed ID: 16330584 This article reviews research on psychosocial treatment for first-episode psychosis.
• Systematic Discovery of the Grammar of Translational Inhibition by RNA Hairpins Journal of Theoretical Biology. Jul, 2006  |   Pubmed ID: 16403535 Recent discovery of gene expression mechanisms has propelled molecular genetics to a state of rapid development, a state likely to persist due to continuing advances in understanding control systems of fundamental cellular processes. An algorithm for that advancement starts in this paper with a gene of interest and a characteristic function of that gene. The set of all genes with counteracting function is identified by pathway searches. Also associated with the first gene is the set of the genes which byproducts of its transcription might downregulate, identified relative to searches involving sequence alignments. Our focus is the intersection of the counteracting gene set and the downregulated gene set. The result is hypothesis generation. Examples of and predictions from this approach are given in the context of apoptosis. Also discussed is application of the algorithm to rational drug design from a new development platform.
• Predictors of Antipsychotic Medication Adherence in Patients Recovering from a First Psychotic Episode Schizophrenia Research. Mar, 2006  |   Pubmed ID: 16529910 Many patients recovering from a first psychotic episode will discontinue medication against medical advice, even before a 1-year treatment course is completed. Factors associated with treatment adherence in patients with chronic schizophrenia include beliefs about severity of illness and need for treatment, treatment with typical versus atypical antipsychotic and medication side effects.
• Effectiveness of Clozapine Versus Olanzapine, Quetiapine, and Risperidone in Patients with Chronic Schizophrenia Who Did Not Respond to Prior Atypical Antipsychotic Treatment The American Journal of Psychiatry. Apr, 2006  |   Pubmed ID: 16585434 When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug, it is unclear what other antipsychotic to switch to and when to use clozapine. In this study, the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness (CATIE) investigation.
• Effectiveness of Olanzapine, Quetiapine, Risperidone, and Ziprasidone in Patients with Chronic Schizophrenia Following Discontinuation of a Previous Atypical Antipsychotic The American Journal of Psychiatry. Apr, 2006  |   Pubmed ID: 16585435 In the treatment of schizophrenia, changing antipsychotics is common when one treatment is suboptimally effective, but the relative effectiveness of drugs used in this strategy is unknown. This randomized, double-blind study compared olanzapine, quetiapine, risperidone, and ziprasidone in patients who had just discontinued a different atypical antipsychotic.
• Review: Longer Duration of Untreated Psychosis is Associated with Worse Outcome in People with First Episode Psychosis Evidence-based Mental Health. May, 2006  |   Pubmed ID: 16638885
• Baseline Neurocognitive Deficits in the CATIE Schizophrenia Trial Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. Sep, 2006  |   Pubmed ID: 16641947 Neurocognition is moderately to severely impaired in patients with schizophrenia. However, the factor structure of the various neurocognitive deficits, the relationship with symptoms and other variables, and the minimum amount of testing required to determine an adequate composite score has not been determined in typical patients with schizophrenia. An 'all-comer' approach to cognition is needed, as provided by the baseline assessment of an unprecedented number of patients in the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) schizophrenia trial. From academic sites and treatment providers representative of the community, 1493 patients with chronic schizophrenia were entered into the study, including those with medical comorbidity and substance abuse. Eleven neurocognitive tests were administered, resulting in 24 individual scores reduced to nine neurocognitive outcome measures, five domain scores and a composite score. Despite minimal screening procedures, 91.2% of patients provided meaningful neurocognitive data. Exploratory principal components analysis yielded one factor accounting for 45% of the test variance. Confirmatory factor analysis showed that a single-factor model comprised of five domain scores was the best fit. The correlations among the factors were medium to high, and scores on individual factors were very highly correlated with the single composite score. Neurocognitive deficits were modestly correlated with negative symptom severity (r=0.13-0.27), but correlations with positive symptom severity were near zero (r
• Single-voxel 1H PRESS at 4.0 T: Precision and Variability of Measurements in Anterior Cingulate and Hippocampus NMR in Biomedicine. Jun, 2006  |   Pubmed ID: 16763968 The precision [coefficient of variation or CV (%) = 100SD/X] of single-voxel point resolved spectroscopic data was characterized bilaterally, in anterior cingulate and in hippocampus, at 4.0 T in a healthy subject. Data acquisition was replicated 10 times after voxel repositioning and readjusting higher order shims. Precision measurements show that the scan-to-scan precision is better in anterior cingulate than in hippocampus, with an average CV of 9.2% (for total NAA, tCho and Cr) in anterior cingulate and 13.9% in hippocampus. Variability measurements made by the same method in 24 healthy subjects and in 29 schizophrenia patients showed that there is substantial biological variability in metabolite levels, even in healthy subjects. Simple calculations suggest that more than 200 subjects would be needed to detect a 5% difference in NAA between patients and controls.
• Clinical Trials in Schizophrenia with Results for the Real World CNS Spectrums. Jul, 2006  |   Pubmed ID: 16816795 Most clinical data for antipsychotics come from studies designed to test the efficacy and safety of the drugs under ideal conditions, in limited subgroups of patients. In contrast, practical clinical trials (PCTs) are designed to test the effectiveness of different treatment options under conditions that more accurately reflect actual clinical practice. Consequently, PCTs are able to provide information that can be utilized by healthcare providers and other decision makers. Characteristics of PCTs include a clinically relevant question, a representative sample of patients and practice settings, sufficient power to identify modest relevant effects, randomization to protect against bias, uncertainty regarding the outcome of treatment, assessment and treatment protocols that enact best clinical practices, simple and relevant outcomes, and limited subject and investigator burden. The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) research program is an example of a PCT. The CATIE study illustrates how PCTs, when properly designed, might be helpful in informing clinical decision making. Because the CATIE study was designed to reflect the effectiveness of antipsychotics under naturalistic clinical conditions, its results should have particular applicability to the arena of clinical practice. This article provides a discussion of the differences between efficacy and effectiveness studies. In assessing the practical utility of results from the CATIE study, much can be learned on how to shape future studies of effectiveness so as to better generate data that are applicable to the "real world."
• A Longitudinal Study of Neurocognitive Function in Individuals At-risk for Psychosis Schizophrenia Research. Dec, 2006  |   Pubmed ID: 16930949 Clinically defined prodromal diagnostic criteria identify at-risk individuals with a 35-40% likelihood of developing a psychotic disorder within a year. The time course and predictive value of cognitive deficits in the development of psychosis has not been established.
• Cost-effectiveness of Second-generation Antipsychotics and Perphenazine in a Randomized Trial of Treatment for Chronic Schizophrenia The American Journal of Psychiatry. Dec, 2006  |   Pubmed ID: 17151158 Second-generation antipsychotics have largely replaced first-generation antipsychotics for the treatment of schizophrenia, but a large-scale cost/effectiveness analysis has not been attempted.
• North American Prodrome Longitudinal Study: a Collaborative Multisite Approach to Prodromal Schizophrenia Research Schizophrenia Bulletin. May, 2007  |   Pubmed ID: 17255119 This article presents the rationale, design, and preliminary findings of the North American Prodrome Longitudinal Study (NAPLS), a collaborative, multisite investigation into the earliest phase of psychotic illness. We describe how 8 independently conceived research projects were integrated methodologically, how diagnostic reliability was achieved across sites on the Structured Interview for Prodromal Syndromes, and how baseline and follow-up data were aggregated for 888 at risk and comparison subjects. Data are presented describing the demographic, academic/work, and diagnostic characteristics of 3 relevant subgroups: persons at heightened clinical risk for psychosis, help-seeking comparison subjects, and nonpsychiatric controls. The NAPLS data set will be used to explore a series of questions related to prodromal psychosis, including the descriptive phenomenology of currently accepted diagnostic criteria, conversion rates over a 30-month period, predictors of psychosis onset and functional disability, and the impact of early treatment on the course of prodromal symptoms.
• MicroRNA Expression in the Prefrontal Cortex of Individuals with Schizophrenia and Schizoaffective Disorder Genome Biology. 2007  |   Pubmed ID: 17326821 microRNAs (miRNAs) are small, noncoding RNA molecules that are now thought to regulate the expression of many mRNAs. They have been implicated in the etiology of a variety of complex diseases, including Tourette's syndrome, Fragile x syndrome, and several types of cancer.
• Effects of Antipsychotic Medications on Psychosocial Functioning in Patients with Chronic Schizophrenia: Findings from the NIMH CATIE Study The American Journal of Psychiatry. Mar, 2007  |   Pubmed ID: 17329467 This study examined the relative effects of the second-generation antipsychotic drugs and an older representative agent on psychosocial functioning in patients with chronic schizophrenia.
• Neuroprotection: a Therapeutic Strategy to Prevent Deterioration Associated with Schizophrenia CNS Spectrums. Mar, 2007  |   Pubmed ID: 17329984 Schizophrenia is a neurodevelopmental disorder associated with persistent symptomatology, severe functional disability, and residual morbidity characteristic of neurodegenerative brain diseases. The illness begins with genetic susceptibility and generally expresses itself after puberty through subtle changes that begin during the prodromal stage. Symptoms get progressively worse and tend to become more resistant to treatment with each relapse. Evidence for a neuroprotective effect of some forms of early treatment is beginning to emerge. While the underlying mechanisms remain uncertain, atypical antipsychotics may counteract some of the progressive deteriorative effects by enhancing synaptic plasticity and cellular resilience. However, identifying and treating patients in the earliest disease states presents methodological challenges as there is no consensus on the best methods of intervention and differences in at-risk children are not readily detectable or substantial enough to predict which ones will develop schizophrenia. In this expert roundtable supplement, Jeffrey A. Lieberman, MD, reviews the historical context of progressive deterioration in schizophrenia. Next, Diana O. Perkins, MD, MPH, reviews some of the challenges to early identification of illness as well as the impact of early versus delayed treatment. Finally, L. Fredrik Jarskog, MD, focuses on the neurobiology of functional progression in schizophrenia as well as pharmacology and the potential for neuroprotection.
• Emotion Perception and Social Skill over the Course of Psychosis: a Comparison of Individuals "at-risk" for Psychosis and Individuals with Early and Chronic Schizophrenia Spectrum Illness Cognitive Neuropsychiatry. May, 2007  |   Pubmed ID: 17453901 Deficits in emotion perception and social skill have been well established in schizophrenia; however, little is known about the extent of these deficits across the course of the illness; that is, prior to illness onset and as the duration of the illness increases.
• Neurocognitive Effects of Antipsychotic Medications in Patients with Chronic Schizophrenia in the CATIE Trial Archives of General Psychiatry. Jun, 2007  |   Pubmed ID: 17548746 Neurocognitive impairment in schizophrenia is severe and is an important predictor of functional outcome. The relative effect of the second-generation (atypical) antipsychotic drugs and older agents on neurocognition has not been comprehensively determined.
• Efficacy and Tolerability of Olanzapine, Quetiapine, and Risperidone in the Treatment of Early Psychosis: a Randomized, Double-blind 52-week Comparison The American Journal of Psychiatry. Jul, 2007  |   Pubmed ID: 17606657 This 52-week randomized, double-blind, flexible-dose, multicenter study evaluated the overall effectiveness (as measured by treatment discontinuation rates) of olanzapine, quetiapine, and risperidone in patients early in the course of psychotic illness.
• Effects of Olanzapine, Quetiapine, and Risperidone on Neurocognitive Function in Early Psychosis: a Randomized, Double-blind 52-week Comparison The American Journal of Psychiatry. Jul, 2007  |   Pubmed ID: 17606658 The authors sought to compare the effects of olanzapine, quetiapine, and risperidone on neurocognitive function in patients with early psychosis.
• Extracting Spurious Messages from Noise and Risk of Schizophrenia-spectrum Disorders in a Prodromal Population The British Journal of Psychiatry : the Journal of Mental Science. Oct, 2007  |   Pubmed ID: 17906248 Atendency to extract spurious, message-like meaning from meaningless noise was assessed as a risk factor leading to schizophrenia-spectrum disorders by assessing word length of speech illusions elicited by multispeaker babble in 43 people with prodromal symptoms. These individuals were randomised to olanzapine v. placebo groups during year 1 followed by no pharmacological treatment for those with no disorder conversion during year 2. A time-dependent Cox regression analysis of conversion to schizophrenia-spectrum disorder revealed a significant interaction between condition (olanzapine v. no drug) and length of speech illusion, with the latter strongly predicting subsequent conversion during medication-free intervals but not during olanzapine treatment.
• Neuroprotection: a New Strategy in the Treatment of Schizophrenia. Early Detection and Intervention CNS Spectrums. Oct, 2007  |   Pubmed ID: 19322959
• Social Functioning in Individuals at Clinical High Risk for Psychosis Schizophrenia Research. Feb, 2008  |   Pubmed ID: 18023329 Poor social functioning is a hallmark of schizophrenia. The purpose of this study was to examine social functioning in individuals at clinical high risk for psychosis. Social functioning was assessed in a sample of 86 clinical high risk (CHR) individuals and compared to that of 50 first-episode of psychosis (FE) subjects, 53 multi-episode schizophrenia subjects (ME) and 55 non-psychiatric controls (NPC). Subjects were assessed on the Social Functioning Scale (SFS), the Role Functioning subscale of the Quality of Life Scale (QLS-role), and the premorbid functioning scale. On the SFS, the CHR group did not differ significantly from the FE and ME groups and all were impaired relative to the NPCs. On QLS-role, the CHR group performed significantly better than the ME patients and significantly worse than NPCs. CHR subjects did not differ from patients in terms of premorbid functioning. This study demonstrates that even at the pre-psychotic phase of the illness, these young people are demonstrating significant deficits in social functioning, supporting that social deficits are present long before the onset of psychotic symptoms.
• Facial Affect Recognition in Individuals at Clinical High Risk for Psychosis The British Journal of Psychiatry : the Journal of Mental Science. Jan, 2008  |   Pubmed ID: 18174514 Facial affect discrimination and identification were assessed in 86 clinical high-risk individuals and compared with 50 individuals with first-episode psychosis, 53 with multi-episode schizophrenia and 55 non-psychiatric controls. On the identification task the non-psychiatric controls performed significantly better than all other groups, and on discrimination significantly better than both patient groups. Deficits in facial affect recognition appear to be present before the onset of psychosis and may be a vulnerability marker.
• Recognizing and Responding to Early Psychosis: a Qualitative Analysis of Individual Narratives Psychiatric Services (Washington, D.C.). Jan, 2008  |   Pubmed ID: 18182546 The ways in which individuals recognize and respond to emerging psychotic illness remain poorly understood. This retrospective study explored when and how individuals recognized changes in themselves and responded to these changes.
• Assessment of Social Judgments and Complex Mental States in the Early Phases of Psychosis Schizophrenia Research. Mar, 2008  |   Pubmed ID: 18255273 Social cognition plays an important role in the functioning of individuals with psychosis. In this study, we explored two areas of social cognition not previously investigated early in the course of psychosis.
• Efficiency of the CATIE and BACS Neuropsychological Batteries in Assessing Cognitive Effects of Antipsychotic Treatments in Schizophrenia Journal of the International Neuropsychological Society : JINS. Mar, 2008  |   Pubmed ID: 18282319 Efficient and reliable assessments of cognitive treatment effects are essential for the comparative evaluation of procognitive effects of pharmacologic therapies. Yet, no studies have addressed the sensitivity and efficiency with which neurocognitive batteries evaluate cognitive abilities before and after treatment. Participants were primarily first episode schizophrenia patients who completed baseline (n = 367) and 12-week (n = 219) assessments with the BACS (Brief Assessment of Cognition in Schizophrenia) and CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) neuropsychological batteries in a clinical trial comparing olanzapine, quetiapine, and risperidone. Exploratory factor analysis revealed that performance on both batteries was characterized by a single factor of generalized cognitive deficit for both baseline performance and cognitive change after treatment. Both batteries estimated similar levels of change following treatment, although the BACS battery required half the administration time. Because a unitary factor characterized baseline cognitive abilities in early psychosis as well as cognitive change after treatment with atypical antipsychotic medications, short batteries such as the BACS may efficiently provide sufficient assessment of procognitive treatment effects with antipsychotic medications. Assessment of cognitive effects of adjunctive therapies targeting specific cognitive domains or impairments may require more extensive testing of the domains targeted to maximize sensitivity for detecting specific predicted cognitive outcomes.
• The Neuregulin 1 Promoter Polymorphism Rs6994992 is Not Associated with Chronic Schizophrenia or Neurocognition American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics. Oct, 2008  |   Pubmed ID: 18286587 The neuregulin 1 (NRG1) promoter single nucleotide polymorphism (SNP) rs6994992 has shown association with decreased activation of frontal and temporal lobe regions, increased risk of psychosis, and decreased premorbid IQ. This SNP is part of a putative schizophrenia risk-associated haplotype and was associated with increased expression of the type IV transcript in postmortem tissue. We tested for association between rs6994992 and chronic schizophrenia by genotyping 738 cases from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and 733 matched controls. We further tested for associations with age at onset and baseline neurocognition in cases with schizophrenia reasoning that these phenotypes might yield results similar to those seen for premorbid IQ. Affection status was weakly associated with rs6994992 genotypes and trended towards association under a recessive model. This association did not survive correction for multiple comparisons and was in the opposite direction than has been reported. There was no association between rs6994992 and age at onset, an estimate of premorbid IQ, or neurocognition at study baseline. We were unable to replicate previous associations of rs6994992 with schizophrenia and, moreover, did not find significant associations with age of onset, an estimate of pre-morbid IQ, or neurocognition.
• Predictors of Treatment Discontinuation and Medication Nonadherence in Patients Recovering from a First Episode of Schizophrenia, Schizophreniform Disorder, or Schizoaffective Disorder: a Randomized, Double-blind, Flexible-dose, Multicenter Study The Journal of Clinical Psychiatry. Jan, 2008  |   Pubmed ID: 18312044 To evaluate predictors of treatment discontinuation against medical advice and poor medication adherence among first-episode patients treated with olanzapine, quetiapine, or risperidone.
• The Graduated Recovery Intervention Program for First Episode Psychosis: Treatment Development and Preliminary Data Community Mental Health Journal. Dec, 2008  |   Pubmed ID: 18516680 The Graduated Recovery Intervention Program (GRIP) is a novel cognitive-behavioral therapy program designed to facilitate functional recovery in people who have experienced an initial episode of psychosis. In this paper, the treatment development process of GRIP is described and data from an open feasibility trial are presented. Findings suggest clinical and psychosocial benefits associated with GRIP, and the treatment was well-received by clients and therapists. The retention rate of 67%, however, suggests the need for protocol modifications to improve engagement. Initial data on the efficacy of GRIP are encouraging, although the study design precludes more robust conclusions at this time.
• A Preliminary Trial of Adherence-coping-education (ACE) Therapy for Early Psychosis The Journal of Nervous and Mental Disease. Jul, 2008  |   Pubmed ID: 18626299 A pilot randomized controlled trial was conducted to examine the effectiveness of adherence-coping-education (ACE) therapy. Twenty-four individuals with early psychosis were randomized to receive 14 sessions of either ACE therapy in addition to treatment as usual, or supportive therapy in addition to treatment as usual. Participants were assessed at baseline, midtreatment, and posttreatment on measures of medication attitudes, psychotic and depressive symptoms, and social functioning. ACE therapy was well tolerated and was associated with significant decrease in symptoms, as well as trend-level improvements in attitudes toward treatment. These results lend initial support for the feasibility of ACE Therapy, and suggest that it may have promise in facilitating recovery for individuals recovering from an initial psychotic episode.
• Neuropsychological Course in the Prodrome and First Episode of Psychosis: Findings from the PRIME North America Double Blind Treatment Study Schizophrenia Research. Oct, 2008  |   Pubmed ID: 18774696 There is uncertainty regarding the onset timing of the cognitive deficiencies of schizophrenia. We investigated whether conversion to psychosis and/or olanzapine altered the neuropsychological course of subjects within the first-ever double blind medication study of the putative schizophrenia first episode prodrome.
• Time-lapse Mapping of Cortical Changes in Schizophrenia with Different Treatments Cerebral Cortex (New York, N.Y. : 1991). May, 2009  |   Pubmed ID: 18842668 Using time-lapse maps, we visualized the dynamics of schizophrenia progression, revealing spreading cortical changes that depend on the type of antipsychotic treatment. Dynamic, 4-dimensional models of disease progression were created from 4 repeated high-resolution brain magnetic resonance imaging scans of 36 first-episode schizophrenia patients (30 men/6 women; mean age: 24.2 +/- 5.1 SD years) randomized to haloperidol (HAL) (n = 15) or olanzapine (OLZ) treatment (n = 21), imaged at baseline, 3, 6, and 12 months (144 scans). Based on surface-based cortical models and point-by-point measures of gray matter volume, we generated time-lapse maps for each treatment. Disease trajectories differed for atypical versus typical neuroleptic drugs. A rapidly advancing parietal-to-frontal deficit trajectory, in HAL-treated patients, mirrored normal cortical maturation but greatly intensified. The disease trajectory advanced even after symptom normalization, involving the frontal cortex within 12 months with typical drug treatment. Areas with fastest tissue loss shifted anteriorly in the first year of psychosis. This trajectory was not seen with OLZ. Whether this association reflects either reduced neurotoxicity or neuroprotection cannot be addressed with neuroimaging; changes may relate to glial rather than neural components. These maps revise current models of schizophrenia progression; due to power limitations, the findings require confirmation in a sample large enough to model group x time interactions.
• Proceedings and Data from The Schizophrenia Summit: a Critical Appraisal to Improve the Management of Schizophrenia The Journal of Clinical Psychiatry. 2009  |   Pubmed ID: 19292973 In mid-February 2008, a panel of 10 nationally recognized schizophrenia research experts was assembled in a Schizophrenia Summit to focus on controversies that exist in treating patients with schizophrenia. The current literature related to the diagnosis and etiopathology of schizophrenia was evaluated regarding the identification of a prodromal phase, brain changes, cognitive impairments, genetic factors, and use of neuroimaging in patients with schizophrenia. Further, consideration was given to evidence supporting the neuroprotective benefits of atypical antipsychotic medications, the benefits of treating patients during the prodromal period, the use of combination antipsychotic medications, the need to improve cognitive function, and the management of substance abuse. Summit faculty member opinion is compared with field survey results, and recommendations are made for future research.
• Validity of the Prodromal Risk Syndrome for First Psychosis: Findings from the North American Prodrome Longitudinal Study Schizophrenia Bulletin. Sep, 2009  |   Pubmed ID: 19386578 Treatment and prevention studies over the past decade have enrolled patients believed to be at risk for future psychosis. These patients were considered at risk for psychosis by virtue of meeting research criteria derived from retrospective accounts of the psychosis prodrome. This study evaluated the diagnostic validity of the prospective "prodromal risk syndrome" construct. Patients assessed by the Structured Interview for Prodromal Syndromes as meeting criteria of prodromal syndromes (n = 377) from the North American Prodrome Longitudinal Study were compared with normal comparison (NC, n = 196), help-seeking comparison (HSC, n = 198), familial high-risk (FHR, n = 40), and schizotypal personality disorder (SPD, n = 49) groups. Comparisons were made on variables from cross-sectional demographic, symptom, functional, comorbid diagnostic, and family history domains of assessment as well as on follow-up outcome. Prodromal risk syndrome patients as a group were robustly distinguished from NC subjects across all domains and distinguished from HSC subjects and from FHR subjects on most measures in many of these domains. Adolescent and young adult SPD patients, while distinct from prodromal patients on definitional grounds, were similar to prodromals on multiple measures, consistent with SPD in young patients possibly being an independent risk syndrome for psychosis. The strong evidence of diagnostic validity for the prodromal risk syndrome for first psychosis raises the question of its evaluation for inclusion in Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition).
• Metabolic Profiles of Second-generation Antipsychotics in Early Psychosis: Findings from the CAFE Study Schizophrenia Research. Jun, 2009  |   Pubmed ID: 19398192 To further define the metabolic profiles of second-generation antipsychotics during the treatment of young patients with early psychosis, with a view to better inform prescribing clinicians.
• The Relation of Antipsychotic and Antidepressant Medication with Baseline Symptoms and Symptom Progression: a Naturalistic Study of the North American Prodrome Longitudinal Sample Schizophrenia Research. Nov, 2009  |   Pubmed ID: 19709859 A substantial number of patients who meet criteria for a prodromal syndrome for first psychosis are treated with antipsychotic and/or antidepressant medications. There is suggestive evidence that both classes of medication may reduce prodromal symptoms. This longitudinal study examined the relation of antipsychotic and antidepressant medication with prodromal symptom severity at baseline and 6-month follow-up. Participants met Structured Interview for Prodromal Syndromes (SIPS) criteria for the prodrome, and were evaluated at eight centers as part of the North American Prodrome Longitudinal Study (NAPLS). Symptom ratings (positive, negative, disorganized and general) and data on antipsychotics, SSRIs, and other antidepressant medications were obtained at baseline and 6-month follow-up. Analyses revealed that all symptom dimensions declined in severity over time, but there were differences in the magnitude of the decline as a function of antipsychotic medication. Those never on antipsychotics showed less reduction in positive and disorganized symptoms over time. SSRIs and other antidepressants were not linked with declines in symptom severity. Consistent with findings from small-sample, clinical trials, the present results suggest that atypical antipsychotics may be effective in reducing the severity of attenuated positive symptoms associated with the prodrome to psychotic disorders. Limitations of the present study are noted, including the fact that it is not a randomized trial, and data on duration and dosage of medication and 2-year follow-up were not available for most participants. The results are discussed in light of the relative risks and benefits of preventive interventions, both medication and cognitive therapies, and the importance of future clinical trials.
• The Effects of Antipsychotic Medications on Emotion Perception in Patients with Chronic Schizophrenia in the CATIE Trial Schizophrenia Research. Nov, 2009  |   Pubmed ID: 19766459 Few pharmacological intervention studies have examined the impact of medication on social cognition, particularly emotion perception. The goal of this randomized, double-blind study is to compare the effects of several second generation antipsychotics and a first generation antipsychotic, perphenazine, on emotion perception in individuals with schizophrenia. Patients were assigned to receive treatment with olanzapine, queitapine fumarate, risperidone, ziprasidone or perphenazine for up to 18 months. Eight hundred and seventy three patients completed an emotion perception test immediately prior to randomization and after 2 months of treatment. We also examined baseline predictors of emotion perception change. Most treatments were associated with a small, non-statistically significant improvement in emotion perception at two months, although they did not differ from one another. Greater improvement in emotion perception at 2 months was significantly predicted by lower baseline emotion perception and higher baseline neurocognitive functioning, and marginally predicted by less time on an antipsychotic.
• Microduplications of 16p11.2 Are Associated with Schizophrenia Nature Genetics. Nov, 2009  |   Pubmed ID: 19855392 Recurrent microdeletions and microduplications of a 600-kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders. We report the association of 16p11.2 microduplications with schizophrenia in two large cohorts. The microduplication was detected in 12/1,906 (0.63%) cases and 1/3,971 (0.03%) controls (P = 1.2 x 10(-5), OR = 25.8) from the initial cohort, and in 9/2,645 (0.34%) cases and 1/2,420 (0.04%) controls (P = 0.022, OR = 8.3) of the replication cohort. The 16p11.2 microduplication was associated with a 14.5-fold increased risk of schizophrenia (95% CI (3.3, 62)) in the combined sample. A meta-analysis of datasets for multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia (P = 4.8 x 10(-7)), bipolar disorder (P = 0.017) and autism (P = 1.9 x 10(-7)). In contrast, the reciprocal microdeletion was associated only with autism and developmental disorders (P = 2.3 x 10(-13)). Head circumference was larger in patients with the microdeletion than in patients with the microduplication (P = 0.0007).
• Discovering Collectively Informative Descriptors from High-throughput Experiments BMC Bioinformatics. 2009  |   Pubmed ID: 20021653 Improvements in high-throughput technology and its increasing use have led to the generation of many highly complex datasets that often address similar biological questions. Combining information from these studies can increase the reliability and generalizability of results and also yield new insights that guide future research.
• Additional Layers of Gene Regulatory Complexity from Recently Discovered MicroRNA Mechanisms The International Journal of Biochemistry & Cell Biology. Aug, 2010  |   Pubmed ID: 20460095 In recent years microRNAs have become recognized as pervasive, versatile agents of gene regulation. Some widely embraced rules involving Watson-Crick hybridization of microRNAs with mRNAs have generated great interest as scientists envision potential RNA cargoes for gene therapy and other experimental systems. However, while researchers ardently seek simplifying principles, nature seems very uncooperative. This article reviews some small RNA mechanisms that potentially regulate genes and which are not covered by previous microRNAs characterizations. In addition, we report here results of fluorescence microscopy experiments to directly demonstrate nuclear import of small RNAs equal in length to typical mature microRNAs, implying that gene regulation at the locus of transcription might be possible.
• No Association of the Serotonin Transporter Polymorphisms 5-HTTLPR and RS25531 with Schizophrenia or Neurocognition American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics. Jul, 2010  |   Pubmed ID: 20468059 A promoter polymorphism in the serotonin transporter gene has been widely studied in neuropsychiatry. We genotyped the 5-HTTLPR/rs25531 triallelic polymorphism in 728 schizophrenia cases from the CATIE study and 724 control subjects. In a logistic regression with case/control status as dependent variable and 7 ancestry-informative principal components as covariates, the effect of 5-HTTLPR/rs25531 composite genotype was not significant (odds ratio = 1.008, 95% CI 0.868-1.172, P = 0.91). In cases only, 5-HTTLPR/rs25531 was not associated with neurocognition (summary neurocognitive index P = 0.21, working memory P = 0.32) or symptomatology (PANSS positive P = 0.67 and negative symptoms P = 0.46). We were unable to identify association of the triallelic 5-HTTLPR with schizophrenia, neurocognition, or core psychotic symptoms even at levels of significance unadjusted for multiple comparisons.
• Neuropsychology of the Prodrome to Psychosis in the NAPLS Consortium: Relationship to Family History and Conversion to Psychosis Archives of General Psychiatry. Jun, 2010  |   Pubmed ID: 20530007 Early detection and prospective evaluation of clinical high-risk (CHR) individuals who may develop schizophrenia or other psychotic disorders is critical for predicting psychosis onset and for testing preventive interventions.
• Psychological Well-being Among Individuals with First-episode Psychosis Early Intervention in Psychiatry. May, 2010  |   Pubmed ID: 20536974 Psychological well-being is a subjective component of quality of life (QOL) that has been previously unexplored in individuals recovering from an initial psychotic episode. This study examined predictors of psychological well-being among individuals with first-episode psychosis (FEP) and compared it to a non-clinical college-aged comparison group.
• Social Skill and Social Cognition in Adolescents at Genetic Risk for Psychosis Schizophrenia Research. Sep, 2010  |   Pubmed ID: 20570111 Adolescents at genetic high risk (GHR) for schizophrenia have shown social skill impairments and there is some evidence to suggest they have Theory of Mind (ToM) deficits; however no research has used a standardized, performance-based behavioral measure to assess social functioning in this population nor evaluated ToM with a well-validated measure. We evaluated the psychometric properties of a new, theoretically-derived assessment of social functioning in GHR adolescents: the "High-Risk Social Challenge" task (HiSoC). The second aim was to explore whether GHR adolescents would show social skill and ToM deficits as compared to a non-psychiatric control (NPC) group. The present study evaluated social functioning with the HiSoC and ToM with the Eyes Test in 23 GHR adolescents and 31 NPCs. The HiSoC demonstrated high levels of reliability and validity. The GHR adolescents showed social skill impairments, but not ToM deficits. The results suggest that the HiSoC is a potentially useful new measure of social functioning in GHR adolescents. Furthermore, the findings add to the current body of literature that indicates that social skill impairments are related to schizophrenia vulnerability.
• Gene Processing Control Loops Suggested by Sequencing, Splicing, and RNA Folding BMC Bioinformatics. 2010  |   Pubmed ID: 21167075 Small RNAs are known to regulate diverse gene expression processes including translation, transcription, and splicing. Among small RNAs, the microRNAs (miRNAs) of 17 to 27 nucleotides (nts) undergo biogeneses including primary transcription, RNA excision and folding, nuclear export, cytoplasmic processing, and then bioactivity as regulatory agents. We propose that analogous hairpins from RNA molecules that function as part of the spliceosome might also be the source of small, regulatory RNAs (somewhat smaller than miRNAs).
• Genome-wide Pharmacogenomic Study of Neurocognition As an Indicator of Antipsychotic Treatment Response in Schizophrenia Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. Feb, 2011  |   Pubmed ID: 21107309 Neurocognitive deficits are a core feature of schizophrenia and, therefore, represent potentially critical outcome variables for assessing antipsychotic treatment response. We performed genome-wide association studies (GWAS) with 492K single nucleotide polymorphisms (SNPs) in a sample of 738 patients with schizophrenia from the Clinical Antipsychotic Trials of Intervention Effectiveness study. Outcome variables consisted of a neurocognitive battery administered at multiple time points over an 18-month period, measuring processing speed, verbal memory, vigilance, reasoning, and working memory domains. Genetic mediation of improvements in each of these five domains plus a composite neurocognitive measure was assessed for each of five antipsychotics (olanzapine, perphenazine, quetiapine, risperidone, and ziprasidone). Six SNPs achieved genome-wide significance using a pre-specified threshold that ensures, on average, only 1 in 10 findings is a false discovery. These six SNPs were located within, or in close proximity to, genes EHF, SLC26A9, DRD2, GPR137B, CHST8, and IL1A. The more robust findings, that is those significant across multiple neurocognitive domains and having adjacent SNPs showing evidence for association, were rs286913 at the EHF gene (p-value 6.99 × 10(-8), q-value 0.034, mediating the effects of ziprasidone on vigilance), rs11240594 at SLC26A9 (p-value 1.4 × 10(-7), q-value 0.068, mediating the effects of olanzapine on processing speed), and rs11677416 at IL1A (p-value 6.67 × 10(-7), q-value 0.081, mediating the effects of olanzapine on working memory). This study has generated several novel candidate genes for antipsychotic response. However, our findings will require replication and functional validation. To facilitate replication efforts, we provide all GWAS p-values for download.
• Nuclear and Cytoplasmic Localization of Neural Stem Cell MicroRNAs RNA (New York, N.Y.). Apr, 2011  |   Pubmed ID: 21363885 Although generally regarded as functional in the cytoplasm, a number of microRNAs (miRNAs) have been found in the nucleus, possibly with a role in gene regulation. Here we report that, in fact, a substantial fraction of all human miRNAs are present in the nucleus of neural stem cells. Further, subsets of these miRNAs display consistently higher standardized rank in the nucleus than in the cytoplasm of these cells, as identified with an RT-qPCR technology and confirmed by microarray analysis. Likewise, other miRNAs display higher cytoplasmic standardized ranks. Three samples were partitioned into nuclear and cytoplasmic fractions in six assays for 373 miRNAs. From the 100 most highly expressed miRNAs, standard scores of nuclear and cytoplasmic concentrations were determined. Among those, 21 miRNAs had all three nuclear standard scores higher than all three cytoplasmic scores; likewise, 31 miRNAs had consistently higher cytoplasmic scores. Random concentrations would result in only five in each set. Remarkably, if one miRNA has a high standard score in a compartment, then other miRNAs having the same 5' seeds and certain similar 3' end patterns are also highly scored in the same way. That is, in addition to the seed sequence, 3' sequence similarity criteria identify families of mature miRNAs with consistently high nuclear or cytoplasmic expression.
• At Clinical High Risk for Psychosis: Outcome for Nonconverters The American Journal of Psychiatry. Aug, 2011  |   Pubmed ID: 21498462 A major focus of early intervention research is determining the risk of conversion to psychosis and developing optimal algorithms of prediction. Although reported rates of nonconversion vary in the literature, the nonconversion rate always encompasses a majority (50%-85%) of the sample participants. Less is known about the outcome among this group, referred to as false positive individuals.
• A Randomized Trial Examining the Effectiveness of Switching from Olanzapine, Quetiapine, or Risperidone to Aripiprazole to Reduce Metabolic Risk: Comparison of Antipsychotics for Metabolic Problems (CAMP) The American Journal of Psychiatry. Sep, 2011  |   Pubmed ID: 21768610 The authors conducted a multisite randomized controlled trial examining the strategy of switching from olanzapine, quetiapine, or risperidone to aripiprazole to ameliorate metabolic risk factors for cardiovascular disease.
• Impaired Neural Synchrony in the Theta Frequency Range in Adolescents at Familial Risk for Schizophrenia Frontiers in Psychiatry / Frontiers Research Foundation. 2011  |   Pubmed ID: 21991257 Puberty is a critical period for the maturation of the fronto-limbic and fronto-striate brain circuits responsible for executive function and affective processing. Puberty also coincides with the emergence of the prodromal signs of schizophrenia, which may indicate an association between these two processes. Time-domain analysis and wavelet based time-frequency analysis was performed on electroencephalographic (EEG) data of 30 healthy control (HC) subjects and 24 individuals at familial risk (FR) for schizophrenia. All participants were between the ages of 13 and 18 years and were carefully matched for age, gender, ethnicity, education, and Tanner Stage. Electrophysiological recordings were obtained from 32 EEG channels while participants performed a visual oddball task, where they identified rare visual targets among standard "scrambled" images and rare aversive and neutral distracter pictures. The time-domain analysis showed that during target processing the FR group showed smaller event-related potentials in the P2 and P3 range as compared to the HC group. In addition, EEG activity in the theta (4-8 Hz) frequency range was significantly reduced during target processing in the FR group. Inefficient cortical information processing during puberty may be an early indicator of altered brain function in adolescents at FR for schizophrenia and may represent a vulnerability marker for illness onset. Longitudinal assessments will have to determine their predictive value for illness onset in populations at FR for psychotic illness.
• Altered Age-related Trajectories of Amygdala-prefrontal Circuitry in Adolescents at Clinical High Risk for Psychosis: a Preliminary Study Schizophrenia Research. Jan, 2012  |   Pubmed ID: 22056201 Emotion processing deficits are prominent in schizophrenia and exist prior to the onset of overt psychosis. However, developmental trajectories of neural circuitry subserving emotion regulation and the role that they may play in illness onset have not yet been examined in patients at risk for psychosis. The present study employed a cross-sectional analysis to examine age-related functional activation in amygdala and prefrontal cortex, as well as functional connectivity between these regions, in adolescents at clinical high risk (CHR) for psychosis relative to typically developing adolescents. Participants (n=34) performed an emotion processing fMRI task, including emotion labeling, emotion matching, and non-emotional control conditions. Regression analyses were used to predict activation in the amygdala and ventrolateral prefrontal cortex (vlPFC) based on age, group, sex, and the interaction of age by group. CHR adolescents exhibited altered age-related variation in amygdala and vlPFC activation, relative to controls. Controls displayed decreased amygdala and increased vlPFC activation with age, while patients exhibited the opposite pattern (increased amygdala and decreased vlPFC activation), suggesting a failure of prefrontal cortex to regulate amygdala reactivity. Moreover, a psychophysiological interaction analysis revealed decreased amygdala-prefrontal functional connectivity among CHR adolescents, consistent with disrupted brain connectivity as a vulnerability factor in schizophrenia. These results suggest that the at-risk syndrome is marked by abnormal development and functional connectivity of neural systems subserving emotion regulation. Longitudinal data are needed to confirm aberrant developmental trajectories intra-individually and to examine whether these abnormalities are predictive of conversion to psychosis, and of later deficits in socioemotional functioning.
• Risk Factors for Psychosis: Impaired Social and Role Functioning Schizophrenia Bulletin. Nov, 2012  |   Pubmed ID: 22080497 Risk for psychosis is currently defined primarily on the basis of attenuated positive symptoms (APS), with no inclusion of the functional deficits characteristic of schizophrenia. Impaired social and role functioning have been of interest for reflecting poor outcome but far less is known about the developmental impact of these deficits as vulnerability or risk factors.
• Evaluation of a Multi-element Treatment Center for Early Psychosis in the United States Social Psychiatry and Psychiatric Epidemiology. Oct, 2012  |   Pubmed ID: 22278376 A growing body of research has demonstrated the potential for comprehensive, phase-specific care to improve clinical and functional outcomes in early psychosis. However, there have been no evaluations of such treatment models in the United States (US). This study is a naturalistic, prospective 1-year follow-up of an early psychosis cohort treated in one of the first US-based multi-element treatment centers.
• Negative Symptoms in Individuals at Clinical High Risk of Psychosis Psychiatry Research. Apr, 2012  |   Pubmed ID: 22445704 Negative symptoms are present in the psychosis prodrome. However, the extent to which these symptoms are present prior to the onset of the first episode of psychosis remains under-researched. The goal of this study is to examine negative symptoms in a sample of individuals at clinical high risk (CHR) for psychosis and to determine if they are predictive of conversion to psychosis. Participants (n=138) were all participants in the North American Prodrome Longitudinal Study (NAPLS 1) project. Negative symptoms were assessed longitudinally using the Scale of Prodromal Symptoms. The mean total negative symptom score at baseline was 11.0, with 82.0% of the sample scoring at moderate severity or above on at least one negative symptom. Over the course of 12 months, the symptoms remained in the above moderate severity range for 54.0% of participants. Associations between individual symptoms were moderate, and a factor analysis confirmed that all negative symptoms loaded heavily on one factor. Negative symptoms were more severe and persistent overtime in those who converted to psychosis, significantly predicting the likelihood of conversion. Thus, early and persistent negative symptoms may represent a vulnerability for risk of developing psychosis.
• North American Prodrome Longitudinal Study (NAPLS 2): Overview and Recruitment Schizophrenia Research. Dec, 2012  |   Pubmed ID: 23043872 The North American Prodrome Longitudinal Study (NAPLS) is a consortium of eight programs focusing on the psychosis prodrome. Funded by the National Institute of Mental Health (NIMH), the sites are located at Emory University, Harvard University, University of Calgary, UCLA, UCSD, University of North Carolina Chapel Hill, Yale University, and Zucker Hillside Hospital. Although the programs initially developed independently, they previously collaborated to combine their historical datasets and to produce a series of analyses on predictors of psychosis in one of the largest samples of longitudinally followed prodromal subjects worldwide. This led to the development of a five year prospective study "Predictors and Mechanisms of Conversion to Psychosis", (also known as NAPLS-2) with three major aims: (1) to prospectively test the prediction algorithm developed in NAPLS-1, (2) to investigate the neuroanatomical, neurophysiological, neurocognitive, and neurohormonal factors that may contribute to the development of psychosis, and (3) to develop a repository of DNA, RNA, and plasma from participants meeting diagnostic criteria for a clinical high risk (CHR) state and from demographically similar healthy subjects. Funded by NIMH in 2008, NAPLS-2 will generate the largest CHR for psychosis sample with 720 CHR and 240 healthy comparison subjects, and thus will provide statistical power and scientific scope that cannot be duplicated by any single site study. This paper describes the overall methodology of the NAPLS-2 project and reports on the ascertainment and demographics at the midway point of the study with (360 CHR) and 180 controls.
• Differences in Subcortical Structures in Young Adolescents at Familial Risk for Schizophrenia: a Preliminary Study Psychiatry Research. Nov, 2012  |   Pubmed ID: 23146250 Schizophrenia has been associated with reduced volumes of subcortical structures on magnetic resonance imaging (MRI), but the relation of these reductions to familial risk for the disorder is unclear. We investigated the effect of familial risk for schizophrenia on regional subcortical volumes during adolescence, a period marked by steep maturational changes in brain structure and the emergence of psychotic symptoms. A group of 26 non-help-seeking, first-degree relatives of patients with schizophrenia and 43 matched healthy comparisons, between 9 and 18 years of age, underwent MRI scanning and were rated for the presence of prodromal symptoms. Five subcortical regions-of-interest were tested for group differences and group by age interactions, as well as correlations with low-level prodromal symptoms in the familial risk group. Relative to comparisons, familial risk subjects demonstrated greater positive volume-age relationships in hippocampus, putamen, and globus pallidus. These results suggest that relatives of individuals with schizophrenia exhibit structural abnormalities in the subcortex as early as pre-adolescence, which may reflect altered neurodevelopment of these regions.
• The Course of Cognitive Functioning over Six Months in Individuals at Clinical High Risk for Psychosis Psychiatry Research. Apr, 2013  |   Pubmed ID: 23159196 Cognitive impairment is common in psychosis and has recently been observed in individuals at clinical high risk (CHR) of developing psychosis. The purpose of this study was to characterize longitudinal change in cognition among CHR individuals, and compare cognition of CHR individuals who later convert to psychosis to that of CHR who do not convert. Participants were tested at baseline and followed-up after six months using a comprehensive cognitive test battery. Individuals who did not convert to psychosis either remained stable or significantly improved in their cognitive performance. At baseline participants who converted to psychosis compared to non-converters exhibited poorer performance in several cognitive tests, suggesting that some cognitive impairment is already present before conversion. Future longitudinal research should address if further decline takes place during the prodrome or after conversion to psychosis.
• Sexual Dimorphisms and Prediction of Conversion in the NAPLS Psychosis Prodrome Schizophrenia Research. Mar, 2013  |   Pubmed ID: 23340377 Sex differences in age at onset, symptomatology, clinical course (see Walker et al., 2002) and functional impairment (Thorup et al., 2007) are well documented in psychosis. The general pattern of findings is that males manifest an earlier onset, more severe symptoms and poorer prognosis than females. Limited studies examining individuals at clinical high-risk (CHR) suggest a similar pattern of sexual dimorphism (Holtzman et al., in review; Corcoran et al., 2011). As part of the North American Prodrome Longitudinal Study (NAPLS), the current study prospectively examined sexual dimorphisms in relationships among CHR symptoms, childhood (premorbid) academic and social functioning, baseline social and role functioning, and conversion to psychosis. Subjects included 276 (113F/163M) CHR NAPLS participants (ages 12-36.8years). All measures/criteria were assessed at baseline except conversion status, assessed at 6-month intervals up to 30months. Results show sex differences in baseline social and role functioning (though not in early childhood adjustment) that predate psychosis onset, with sexually dimorphic patterns in relation to prodromal symptoms. Among male (but not female) CHRs, baseline social functioning and positive prodromal symptoms predicted conversion. These findings help elucidate early course of vulnerability for, and maximally sensitive and specific etiological and prediction models of, psychosis conversion. Findings highlight the importance of considering sexually differentiated predictors of longitudinal course and outcome, in the context of emerging risk profiles. This may optimize efforts at early identification and individually tailored preventive interventions targeting different neurobiological markers/systems and/or cognitive-behavioral approaches. We speculate a contemporary, multidimensional model of psychosis risk that posits a role of sexually dimorphic, genetically linked influences that converge with a modulating role of gonadal hormones (see Walder et al., 2012) across a temporally sensitive neurodevelopmental trajectory towards conferring risk.
• Early Traumatic Experiences in Those at Clinical High Risk for Psychosis Early Intervention in Psychiatry. Aug, 2013  |   Pubmed ID: 23343384 Several lines of evidence suggest a possible association between a history of trauma in childhood and later psychosis or psychotic-like experiences. The purpose of this study was to determine the extent of childhood trauma and bullying in young people at clinical high risk (CHR) of developing psychosis.
• Altered Fronto-limbic Activity in Children and Adolescents with Familial High Risk for Schizophrenia Psychiatry Research. Apr, 2013  |   Pubmed ID: 23482245 Early symptoms of schizophrenia tend to emerge during adolescence, hich is a critical period for development of executive and emotional processing. While individuals with familial high risk (FHR) for schizophrenia may show cognitive and emotional changes, the neural mechanisms underlying the development of these changes remain unclear. The goal of this study was to identify functional differences in fronto-striato-limbic regions in children with FHR. Functional magnetic resonance imaging (MRI) data were collected from 21 children with a first-degree family member with schizophrenia and 21 controls without FHR. Participants performed an emotional oddball task requiring both selective attention and suppression of task-irrelevant emotional information. During selective attention, the group with FHR showed enhanced activation in the inferior frontal gyrus and caudate, with decreases in middle frontal gyrus and insular activation. The FHR group also showed greater age-related recruitment of anterior cingulate, temporal and occipital cortical areas during selective attention. During emotional processing, the FHR group showed decreased anterior cingulate activation, with decreased age-related recruitment of inferior frontal, parietal and occipital areas. The results suggest that FHR for schizophrenia may be associated with abnormal hyperactivation and hypoactivation of the neural circuitry engaged during executive and emotional processing and with age-related changes in neural recruitment during adolescence.
• Cortisol Levels and Risk for Psychosis: Initial Findings from the North American Prodrome Longitudinal Study Biological Psychiatry. Sep, 2013  |   Pubmed ID: 23562006 Studies of biomarkers of hypothalamic-pituitary-adrenal activity indicate that psychotic disorders are associated with elevated cortisol. This study examined cortisol levels in healthy control subjects and individuals who met clinical high-risk (CHR) criteria for psychosis. It was hypothesized that cortisol levels would be 1) elevated in the CHR group relative to control subjects, 2) positively correlated with symptom severity, and 3) most elevated in CHR patients who transition to psychotic level severity.
• The Genomic Psychiatry Cohort: Partners in Discovery American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics. Jun, 2013  |   Pubmed ID: 23650244 The Genomic Psychiatry Cohort (GPC) is a longitudinal resource designed to provide the necessary population-based sample for large-scale genomic studies, studies focusing on Research Domain Criteria (RDoC) and/or other alternate phenotype constructs, clinical and interventional studies, nested case-control studies, long-term disease course studies, and genomic variant-to-phenotype studies. We provide and will continue to encourage access to the GPC as an international resource. DNA and other biological samples and diagnostic data are available through the National Institute of Mental Health (NIMH) Repository. After appropriate review and approval by an advisory board, investigators are able to collaborate in, propose, and co-lead studies involving cohort participants.
• Psychotropic Medication Use in Youth at High Risk for Psychosis: Comparison of Baseline Data from Two Research Cohorts 1998-2005 and 2008-2011 Schizophrenia Research. Aug, 2013  |   Pubmed ID: 23787224 Antipsychotic medication use rates have generally been rising among youth with psychiatric disorders, but little is known about use rates of antipsychotics or other psychotropic medications in patients at high risk for psychosis.
• Between-site Reliability of Startle Prepulse Inhibition Across Two Early Psychosis Consortia Neuroreport. Aug, 2013  |   Pubmed ID: 23799460 Prepulse inhibition (PPI) and reactivity of the acoustic startle response are widely used biobehavioral markers in psychopathology research. Previous studies have demonstrated that PPI and startle reactivity exhibit substantial within-site stability; however, between-site stability has not been established. In two separate consortia investigating biomarkers of early psychosis, traveling participants studies were carried out as a part of quality assurance procedures to assess the fidelity of data across sites. In the North American Prodromal Longitudinal Studies (NAPLS) consortium, eight normal participants traveled to each of the eight NAPLS sites and were tested twice at each site on the startle PPI paradigm. In preparation for a binational study, 10 healthy participants were assessed twice in both San Diego and Mexico City. Intraclass correlations between and within sites were significant for PPI and startle response parameters, confirming the reliability of startle measures across sites in both consortia. There were between-site differences in startle magnitude in the NAPLS study that did not appear to be related to methods or equipment. In planning multisite studies, it is essential to institute quality assurance procedures early and establish between-site reliability to assure comparable data across sites.
• Social Cognition As a Mediator Between Neurocognition and Functional Outcome in Individuals at Clinical High Risk for Psychosis Schizophrenia Research. Nov, 2013  |   Pubmed ID: 24012459 In schizophrenia, neurocognition, social cognition and functional outcome are all inter-related, with social cognition mediating the impact that impaired neurocognition has on functional outcome. Less clear is the nature of the relationship between neurocognition, social cognition and functional outcome in individuals at clinical high risk (CHR) for psychosis. 137 CHR participants completed a neurocognitive test battery, a battery of social cognition tasks and the Social Functioning Scale. Confirmatory factor analysis showed that all social cognition tasks were reliable and valid measures of the latent variable. The path from neurocognition to functioning was statistically significant (standardized coefficient β=0.22, p
• Premorbid Functional Development and Conversion to Psychosis in Clinical High-risk Youths Development and Psychopathology. Nov, 2013  |   Pubmed ID: 24229556 Deterioration in premorbid functioning is a common feature of schizophrenia, but sensitivity to psychosis conversion among clinical high-risk samples has not been examined. This study evaluates premorbid functioning as a predictor of psychosis conversion among a clinical high-risk sample, controlling for effects of prior developmental periods. Participants were 270 clinical high-risk individuals in the North American Prodrome Longitudinal Study-I, 78 of whom converted to psychosis over the next 2.5 years. Social, academic, and total maladjustment in childhood, early adolescence, and late adolescence were rated using the Cannon-Spoor Premorbid Adjustment Scale. Early adolescent social dysfunction significantly predicted conversion to psychosis (hazard ratio = 1.30, p = .014), independently of childhood social maladjustment and independently of severity of most baseline positive and negative prodromal symptoms. Baseline prodromal symptoms of disorganized communication, social anhedonia, suspiciousness, and diminished ideational richness mediated this association. Early adolescent social maladjustment and baseline suspiciousness together demonstrated moderate positive predictive power (59%) and high specificity (92.1%) in predicting conversion. Deterioration of academic and total functioning, although observed, did not predict conversion to psychosis. Results indicate early adolescent social dysfunction to be an important early predictor of conversion. As such, it may be a good candidate for inclusion in prediction algorithms and could represent an advantageous target for early intervention.
• Metacognitive Functioning in Individuals at Clinical High Risk for Psychosis Behavioural and Cognitive Psychotherapy. Sep, 2014  |   Pubmed ID: 23517866 Metacognition has been described as the knowledge of our own cognitive processes. Metacognitive deficits are common in schizophrenia, but little is known about metacognition before the onset of full-blown psychosis.
• Perceived Discrimination in Those at Clinical High Risk for Psychosis Early Intervention in Psychiatry. Feb, 2014  |   Pubmed ID: 23773288 There is evidence to suggest that perceived discrimination may be associated with psychosis. Less is known about its potential impact on those at clinical high risk (CHR) for psychosis. The aim of this study was to determine the prevalence of perceived discrimination in a CHR sample and its possible relationship to attenuated positive symptoms and negative self-beliefs.
• Functional Development in Clinical High Risk Youth: Prediction of Schizophrenia Versus Other Psychotic Disorders Psychiatry Research. Jan, 2014  |   Pubmed ID: 24200216 This study evaluates premorbid social and academic functioning in clinical high-risk individuals as predictors of transition to schizophrenia versus another psychotic disorder. Participants were 54 individuals enrolled in phase one of the North American Prodrome Longitudinal Study who over two and a half years of follow-up met criteria for schizophrenia/schizophreniform disorder (n=28) or another psychotic disorder (n=26). Social and academic functioning in childhood, early adolescence, and late adolescence was assessed at baseline using the Cannon-Spoor Premorbid Adjustment Scale. Social maladjustment in late adolescence predicted significantly higher odds of transition to schizophrenia versus another psychotic disorder independent of childhood and early adolescent adjustment (OR=4.02) and conveyed unique risk over academic maladjustment (OR=5.64). Premorbid academic maladjustment was not associated with psychotic disorder diagnosis. Results support diagnostic specificity of premorbid social dysfunction to schizophrenia in clinical high-risk youth and underscore an important role for social maladjustment in the developmental pathology of schizophrenia and its prediction.
• The Relationship of Neurocognition and Negative Symptoms to Social and Role Functioning over Time in Individuals at Clinical High Risk in the First Phase of the North American Prodrome Longitudinal Study Schizophrenia Bulletin. Nov, 2014  |   Pubmed ID: 24550526 Impaired social, role, and neurocognitive functioning are preillness characteristics of people who later develop psychosis. In people with schizophrenia, neurocognition and negative symptoms are associated with functional impairment. We examined the relative contributions of neurocognition and symptoms to social and role functioning over time in clinically high-risk (CHR) individuals and determined if negative symptoms mediated the influence of cognition on functioning.
• Reliability of Functional Magnetic Resonance Imaging Activation During Working Memory in a Multi-site Study: Analysis from the North American Prodrome Longitudinal Study NeuroImage. Aug, 2014  |   Pubmed ID: 24736173 Multi-site neuroimaging studies offer an efficient means to study brain functioning in large samples of individuals with rare conditions; however, they present new challenges given that aggregating data across sites introduces additional variability into measures of interest. Assessing the reliability of brain activation across study sites and comparing statistical methods for pooling functional data are critical to ensuring the validity of aggregating data across sites. The current study used two samples of healthy individuals to assess the feasibility and reliability of aggregating multi-site functional magnetic resonance imaging (fMRI) data from a Sternberg-style verbal working memory task. Participants were recruited as part of the North American Prodrome Longitudinal Study (NAPLS), which comprises eight fMRI scanning sites across the United States and Canada. In the first study sample (n=8), one participant from each home site traveled to each of the sites and was scanned while completing the task on two consecutive days. Reliability was examined using generalizability theory. Results indicated that blood oxygen level-dependent (BOLD) signal was reproducible across sites and was highly reliable, or generalizable, across scanning sites and testing days for core working memory ROIs (generalizability ICCs=0.81 for left dorsolateral prefrontal cortex, 0.95 for left superior parietal cortex). In the second study sample (n=154), two statistical methods for aggregating fMRI data across sites for all healthy individuals recruited as control participants in the NAPLS study were compared. Control participants were scanned on one occasion at the site from which they were recruited. Results from the image-based meta-analysis (IBMA) method and mixed effects model with site covariance method both showed robust activation in expected regions (i.e. dorsolateral prefrontal cortex, anterior cingulate cortex, supplementary motor cortex, superior parietal cortex, inferior temporal cortex, cerebellum, thalamus, basal ganglia). Quantification of the similarity of group maps from these methods confirmed a very high (96%) degree of spatial overlap in results. Thus, brain activation during working memory function was reliable across the NAPLS sites and both the IBMA and mixed effects model with site covariance methods appear to be valid approaches for aggregating data across sites. These findings indicate that multi-site functional neuroimaging can offer a reliable means to increase power and generalizability of results when investigating brain function in rare populations and support the multi-site investigation of working memory function in the NAPLS study, in particular.
• Exploratory Analysis of Social Cognition and Neurocognition in Individuals at Clinical High Risk for Psychosis Psychiatry Research. Aug, 2014  |   Pubmed ID: 24755041 Neurocognition and social cognition are separate but related constructs known to be impaired in schizophrenia. The aim of this study was to extend the current knowledge of the relationship between social cognition and neurocognition in individuals at clinical high risk (CHR) of developing psychosis by examining, in a large sample, the associations between a wide range of neurocognitive tasks and social cognition. Participants included 136 young people at CHR. Specific domains within neurocognition and social cognition were compared using Spearman correlations. Results showed that poor theory of mind correlated with low ratings on a wide range of neurocognitive tasks. Facial affect was more often associated with low ratings on spatial working memory and attention. These results support a link between neurocognition and social cognition even at this early stage of potential psychosis, with indication that poorer performance on social cognition may be associated with deficits in attention and working memory. Understanding these early associations may have implications for early intervention.
• A Naturalistic Comparison of the Long-term Metabolic Adverse Effects of Clozapine Versus Other Antipsychotics for Patients with Psychotic Illnesses Journal of Clinical Psychopharmacology. Aug, 2014  |   Pubmed ID: 24943389 Clozapine, an evidence-based treatment of refractory schizophrenia, is associated with increased weight gain and metabolic dysregulation compared with most antipsychotics in short-term clinical trials. However, there are limited data describing comparative long-term metabolic risks. In this report, we examined whether short-term differences persist with long-term exposure to clozapine.
• Current Status Specifiers for Patients at Clinical High Risk for Psychosis Schizophrenia Research. Sep, 2014  |   Pubmed ID: 25012147 Longitudinal studies of the clinical high risk (CHR) syndrome for psychosis have emphasized the conversion vs non-conversion distinction and thus far have not focused intensively on classification among non-converters. The present study proposes a system for classifying CHR outcomes over time when using the Structured Interview for Psychosis-risk Syndromes and evaluates its validity.
• The Content of Attenuated Psychotic Symptoms in Those at Clinical High Risk for Psychosis Psychiatry Research. Nov, 2014  |   Pubmed ID: 25048759 Recent research has started to focus on identifying individuals who are at clinical high risk of developing psychosis as a means to try and understand the predictors and mechanisms involved in the progress to a full psychotic episode. The aim of the current study was to provide an initial description and prevalence rates of specific content found within attenuated positive symptoms. The Content of Attenuated Positive Symptoms (CAPS) codebook was used by independent raters to determine the presence of content within a sample of written vignettes. Krippendorff's alpha was used to determine inter-rater reliability. Overall, the majority of items fell in or above an acceptable range of reliability. There was heterogeneity present in the types of content endorsed. However, the most commonly endorsed items included being perplexed by reality, increased hypervigilence, being gifted, hearing indistinct and distinct sounds, seeing figures or shadows, something touching the individual, and unpleasant smells. The use of the CAPS codebook is a reliable way to code the content of attenuated positive symptoms. Identifying and monitoring the presence of certain content may provide insight into the presence of other comorbid issues and the potential for future conversion.
• Movement Abnormalities Predict Transitioning to Psychosis in Individuals at Clinical High Risk for Psychosis Schizophrenia Research. Nov, 2014  |   Pubmed ID: 25311779 Improving upon the predictive validity of determining the transition from high risk to actual psychosis is a primary aim of early intervention research. Previous research has suggested that premorbid spontaneous dyskinesias may be one possible predictor. In this study, dyskinetic movements were assessed with the Abnormal Involuntary Movement Scale (AIMS) at baseline of a longitudinal study of 148 individuals at clinical high risk (CHR) of developing psychosis. Twenty-eight individuals transitioned to a psychotic disorder over the course of the study. Group comparisons between transitioned and non-transitioned individuals indicated that, relative to those that were not observed to transition, participants that developed a psychotic disorder exhibited greater spontaneous dyskinesias at baseline. Moreover, increased dyskinetic movements at baseline resulted in a more than two-fold increase in odds of developing a psychosis for each point increase in AIMS scale score. These findings suggest that individuals with greater premorbid dyskinetic movements may comprise a subset of CHR individuals at inordinate risk to decompensate into psychosis. Future work should employ assessments of spontaneous dyskinesias by instrumentation (e.g., electromyography) and look to ascertain whether specific dyskinesias (e.g., dystonia) or dyskinesias of specific body regions are associated with transitioning to psychosis.
• Stress Exposure and Sensitivity in the Clinical High-risk Syndrome: Initial Findings from the North American Prodrome Longitudinal Study (NAPLS) Schizophrenia Research. Dec, 2014  |   Pubmed ID: 25443665 There is inconsistent evidence for increased stress exposure among individuals at clinical high risk (CHR) for psychosis. Yet similar to patients with a diagnosed psychotic illness, the preponderance of evidence suggests that CHR individuals tend to experience stressful life events (LE) and daily hassles (DH) as more subjectively stressful than healthy individuals. The present study utilizes data from the North American Prodrome Longitudinal Study Phase 2 (NAPLS-2) to test the hypotheses that (1) CHR individuals manifest higher self-reported stress in response to both LE and DH when compared to healthy controls (HC), (2) group differences in self-reported stress increase with age, (3) baseline self-reported stress is associated with follow-up clinical status, and (4) there is a sensitization effect of LE on the response to DH. In contrast to some previous research, the present findings indicate that the CHR group (N=314) reported exposure to more LE when compared to the HC group (N=162). As predicted, CHR participants rated events as more stressful, and those who progressed to psychosis reported a greater frequency of LE and greater stress from events compared to those whose prodromal symptoms remitted. There was also some evidence of stress-sensitization; those who experienced more stress from LE rated current DH as more stressful. The results indicate that the "prodromal" phase is a period of heightened stress and stress sensitivity, and elevated cumulative lifetime exposure to stressful events may increase reactions to current stressors.
• Negative Symptoms and Impaired Social Functioning Predict Later Psychosis in Latino Youth at Clinical High Risk in the North American Prodromal Longitudinal Studies Consortium Early Intervention in Psychiatry. Dec, 2015  |   Pubmed ID: 24576057 Examining ethnically related variables in evaluating those at risk for psychosis is critical. This study investigated sociodemographic and clinical characteristics of Latino versus non-Latino clinical high-risk (CHR) subjects and healthy control (HC) subjects in the first North American Prodrome Longitudinal Study.
• Personal Beliefs About Experiences in Those at Clinical High Risk for Psychosis Behavioural and Cognitive Psychotherapy. Nov, 2015  |   Pubmed ID: 24949991 Negative beliefs about illness in early psychosis have been shown to have an unfavourable impact on one's quality of life. A shift of focus in psychosis research has been on the detection of individuals considered to be at clinical high risk (CHR) of developing psychosis. Little is known about the impact that beliefs about psychotic like experiences or attenuated psychotic symptoms may have on CHR individuals.
• Towards a Psychosis Risk Blood Diagnostic for Persons Experiencing High-risk Symptoms: Preliminary Results from the NAPLS Project Schizophrenia Bulletin. Mar, 2015  |   Pubmed ID: 25103207 A barrier to preventative treatments for psychosis is the absence of accurate identification of persons at highest risk. A blood test that could substantially increase diagnostic accuracy would enhance development of psychosis prevention interventions.
• Reliability of an FMRI Paradigm for Emotional Processing in a Multisite Longitudinal Study Human Brain Mapping. Jul, 2015  |   Pubmed ID: 25821147 Multisite neuroimaging studies can facilitate the investigation of brain-related changes in many contexts, including patient groups that are relatively rare in the general population. Though multisite studies have characterized the reliability of brain activation during working memory and motor functional magnetic resonance imaging tasks, emotion processing tasks, pertinent to many clinical populations, remain less explored. A traveling participants study was conducted with eight healthy volunteers scanned twice on consecutive days at each of the eight North American Longitudinal Prodrome Study sites. Tests derived from generalizability theory showed excellent reliability in the amygdala ( Eρ2 = 0.82), inferior frontal gyrus (IFG; Eρ2 = 0.83), anterior cingulate cortex (ACC; Eρ2 = 0.76), insula ( Eρ2 = 0.85), and fusiform gyrus ( Eρ2 = 0.91) for maximum activation and fair to excellent reliability in the amygdala ( Eρ2 = 0.44), IFG ( Eρ2 = 0.48), ACC ( Eρ2 = 0.55), insula ( Eρ2 = 0.42), and fusiform gyrus ( Eρ2 = 0.83) for mean activation across sites and test days. For the amygdala, habituation ( Eρ2 = 0.71) was more stable than mean activation. In a second investigation, data from 111 healthy individuals across sites were aggregated in a voxelwise, quantitative meta-analysis. When compared with a mixed effects model controlling for site, both approaches identified robust activation in regions consistent with expected results based on prior single-site research. Overall, regions central to emotion processing showed strong reliability in the traveling participants study and robust activation in the aggregation study. These results support the reliability of blood oxygen level-dependent signal in emotion processing areas across different sites and scanners and may inform future efforts to increase efficiency and enhance knowledge of rare conditions in the population through multisite neuroimaging paradigms.
• Core Schemas in Youth at Clinical High Risk for Psychosis Behavioural and Cognitive Psychotherapy. Apr, 2015  |   Pubmed ID: 25896713 Schema Theory proposes that the development of maladaptive schemas are based on a combination of memories, emotions and cognitions regarding oneself and one's relationship to others. A cognitive model of psychosis suggests that schemas are crucial to the development and persistence of psychosis. Little is known about the impact that schemas may have on those considered to be at clinical high risk (CHR) of developing psychosis.
• North American Prodrome Longitudinal Study (NAPLS 2): The Prodromal Symptoms The Journal of Nervous and Mental Disease. May, 2015  |   Pubmed ID: 25919383 In studies describing the long-term follow-up up of youth at clinical high risk (CHR) of psychosis, little attention has been given to details of specific prodromal symptoms. In this paper, we describe the prodromal symptoms of 764 CHR participants recruited in the multi-site North American Prodrome Longitudinal Study (NAPLS). Symptoms were rated on the Scale of Prodromal Symptoms (SOPS) at baseline and 6-, 12-, 18-, and 24-month follow-ups. Clinical outcome at the 2-year assessment was categorized as psychotic, prodromal progression, symptomatic or in remission. Most of the CHR sample (92%) met criteria for the attenuated positive symptoms syndrome (APSS). Significant improvements in SOPS symptoms were observed over time. Unusual thought content, disorganized communication, and overall ratings on disorganized symptoms differentiated those who transitioned to psychosis from the other clinical outcome groups. Suspiciousness and total positive symptoms differentiated those in remission from the other clinical outcome groups.
• Demographic Correlates of Attenuated Positive Psychotic Symptoms Schizophrenia Research. Aug, 2015  |   Pubmed ID: 25999040 It is now well established that the utilization of standardized clinical criteria can enhance prediction of psychosis. These criteria are primarily concerned with the presence and severity of attenuated positive symptoms. Because these symptom criteria are used to derive algorithms for designating clinical high risk (CHR) status and for maximizing prediction of psychosis risk, it is important to know whether the symptom ratings vary as a function of demographic factors that have previously been linked with symptoms in diagnosed psychotic patients. Using a sample of 356 CHR individuals from the NAPLS-II multi-site study, we examined the relation of three sex, age, and educational level, with the severity of attenuated positive symptom scores from the Scale of Prodromal Symptoms (SOPS). Demographic factors accounted for little of the variance in symptom ratings (5-6%). Older CHR individuals manifested more severe suspiciousness, and female CHR participants reported more unusual perceptual experiences than male participants. Contrary to prediction, higher educational level was associated with more severe ratings of unusual thought content, but less severe perceptual abnormalities. Overall, sex, age and education were modestly related to unusual thought content and perceptual abnormalities, only, suggesting minimal implication for designating CHR status and predicting psychosis-risk.
• The Management of Schizophrenia in Clinical Practice (MOSAIC) Registry: a Focus on Patients, Caregivers, Illness Severity, Functional Status, Disease Burden and Healthcare Utilization Schizophrenia Research. Aug, 2015  |   Pubmed ID: 26027848 The Management of Schizophrenia in Clinical Practice (MOSAIC), a disease-based registry of schizophrenia, was initiated in December 2012 to address important gaps in our understanding of the impact and burden of schizophrenia and to provide insight into the current status of schizophrenia care in the US. Recruitment began in December 2012 with ongoing assessment continuing through May 2014.
• Association of Thalamic Dysconnectivity and Conversion to Psychosis in Youth and Young Adults at Elevated Clinical Risk JAMA Psychiatry. Sep, 2015  |   Pubmed ID: 26267151 Severe neuropsychiatric conditions, such as schizophrenia, affect distributed neural computations. One candidate system profoundly altered in chronic schizophrenia involves the thalamocortical networks. It is widely acknowledged that schizophrenia is a neurodevelopmental disorder that likely affects the brain before onset of clinical symptoms. However, no investigation has tested whether thalamocortical connectivity is altered in individuals at risk for psychosis or whether this pattern is more severe in individuals who later develop full-blown illness.
• Specificity of Incident Diagnostic Outcomes in Patients at Clinical High Risk for Psychosis Schizophrenia Bulletin. Sep, 2015  |   Pubmed ID: 26272875 It is not well established whether the incident outcomes of the clinical high-risk (CHR) syndrome for psychosis are diagnostically specific for psychosis or whether CHR patients also are at elevated risk for a variety of nonpsychotic disorders. We collected 2 samples (NAPLS-1, PREDICT) that contained CHR patients and a control group who responded to CHR recruitment efforts but did not meet CHR criteria on interview (help-seeking comparison patients [HSC]). Incident diagnostic outcomes were defined as the occurrence of a SIPS-defined psychosis or a structured interview diagnosis from 1 of 3 nonpsychotic Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) groups (anxiety, bipolar, or nonbipolar mood disorder), when no diagnosis in that group was present at baseline. Logistic regression revealed that the CHR vs HSC effect did not vary significantly across study for any emergent diagnostic outcome; data from the 2 studies were therefore combined. CHR (n = 271) vs HSC (n = 171) emergent outcomes were: psychosis 19.6% vs 1.8%, bipolar disorders 1.1% vs 1.2%, nonbipolar mood disorders 4.4% vs 5.3%, and anxiety disorders 5.2% vs 5.3%. The main effect of CHR vs HSC was statistically significant (OR = 13.8, 95% CI 4.2-45.0, df = 1, P < .001) for emergent psychosis but not for any emergent nonpsychotic disorder. Sensitivity analyses confirmed these findings. Within the CHR group emergent psychosis was significantly more likely than each nonpsychotic DSM-IV emergent disorder, and within the HSC group emergent psychosis was significantly less likely than most emergent nonpsychotic disorders. The CHR syndrome is specific as a marker for research on predictors and mechanisms of developing psychosis.
• Severity of Thought Disorder Predicts Psychosis in Persons at Clinical High-risk Schizophrenia Research. Oct, 2015  |   Pubmed ID: 26441004 Improving predictive accuracy is of paramount importance for early detection and prevention of psychosis. We sought a symptom severity classifier that would improve psychosis risk prediction.
• Anxiety in Youth at Clinical High Risk for Psychosis Early Intervention in Psychiatry. Oct, 2015  |   Pubmed ID: 26456932 High rates of anxiety have been observed in youth at clinical high risk (CHR) of developing psychosis. In CHR, anxiety often co-occurs with depression, and there is inconsistent evidence on anxiety in relation to transition to psychosis. The aim of this study was to examine: (i) the prevalence of anxiety disorders in individuals at CHR; (ii) clinical differences between those with and without anxiety; and (iii) the association of baseline anxiety with later transition to psychosis.
• Evaluating the Impact of Cannabis Use on Thalamic Connectivity in Youth at Clinical High Risk of Psychosis BMC Psychiatry. 2015  |   Pubmed ID: 26553191 Disruptions in thalamic functional connectivity have been observed in people with schizophrenia and in youth at clinical high risk (CHR) of psychosis. However, the impact of environmental risk factors for psychosis on thalamic dysconnectivity is poorly understood. We tested whether thalamic dysconnectivity is related to patterns of cannabis use in a CHR sample.
• The Dark Side of the Moon: Meta-analytical Impact of Recruitment Strategies on Risk Enrichment in the Clinical High Risk State for Psychosis Schizophrenia Bulletin. Nov, 2015  |   Pubmed ID: 26591006 The individual risk of developing psychosis after being tested for clinical high-risk (CHR) criteria (posttest risk of psychosis) depends on the underlying risk of the disease of the population from which the person is selected (pretest risk of psychosis), and thus on recruitment strategies. Yet, the impact of recruitment strategies on pretest risk of psychosis is unknown.