Showing papers by "Barbara A. Cornblatt published in 2007"

Preliminary Findings for Two New Measures of Social and Role Functioning in the Prodromal Phase of Schizophrenia

Abstract: Introduction: Research on prediction and prevention of schizophrenia has increasingly focused on prodromal (prepsychosis) social and role dysfunction as developmentally early, stable, and treatment-resistant illness components. In this report, 2 new measures, Global Functioning: Social and Global Functioning: Role, are presented, along with preliminary findings about psychometric properties and course of social and role (academic/work) functioning in the prodromal phase of psychosis. Methods: Subjects included 69 participants from the Recognition and Prevention program and 52 from the Center for the Assessment and Prevention of Prodromal States. Ages ranged from 12 to 29 years, and all met criteria for Attenuated Positive Symptom syndrome. Retrospective (past year) and baseline data are reported for all 121 prodromal subjects and for 44 normal controls (NCs). Prospective follow-up data are reported for a subsample of patients reevaluated at both 6 and 12 months (N = 44). Results: For both scales, inter-rater reliability was high, and preliminary data supported construct validity. Relative to NCs, prodromal individuals displayed impaired social and role functioning at baseline. Analyses of change over time indicated that role functioning declined over the year before ascertainment and improved over 12-month follow-up, presumably with treatment. Social impairment, by contrast, was constant across time and predicted later psychosis (P = .002). Discussion: Using 2 new global measures, social functioning was found to be a stable trait, unchanged by treatment, with considerable potential to be a marker of schizophrenia. Role functioning, by contrast, may be a more direct barometer of clinical change and may be responsive to treatment and environmental change.

North American Prodrome Longitudinal Study: A Collaborative Multisite Approach to Prodromal Schizophrenia Research

Abstract: 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.

Can antidepressants be used to treat the schizophrenia prodrome? Results of a prospective, naturalistic treatment study of adolescents.

Abstract: OBJECTIVE This study reports the results of a prospective, naturalistic treatment study of adolescents considered to be in the prodromal (i.e., prepsychotic) phase of schizophrenia. METHOD Forty-eight adolescents (mean age = 15.8 years) participating in the initial phase of the Recognition and Prevention (RAP) program (1998-2005) were included in the current report. Individuals were selected from the overall sample (N = 152) if they had: (1) displayed attenuated positive symptoms, (2) been treated pharmacologically for at least 8 weeks, and (3) been followed up for at least 6 months (mean follow-up = 30.5 months). RESULTS Two types of medication were naturalistically prescribed: antidepressants (N = 20) or second-generation antipsychotics (N = 28), with polypharmacy common. The 2 treatment groups did not differ in baseline symptom profiles, with the exception of disorganized thinking, which was more severe in second-generation antipsychotic-treated adolescents. Twelve of the 48 adolescents (25%) developed a psychotic disorder, with all converters having been prescribed second-generation antipsychotics. There were no conversions among antidepressant-treated adolescents (log-rank chi(2) = 7.36, df = 1, p = .007). Treatment outcome, however, was confounded, since 11 of the 12 converters were nonadherent. Adolescents, in general, were more likely to be nonadherent to second-generation antipsychotics (61%, 17/28) than to antidepressants (20%, 4/20; chi(2) = 7.86, p = .005). Improvement in 3 of 5 positive symptoms over time was significant (p < .001) and similar for both medications. Disorganized thought, however, did not improve regardless of treatment. CONCLUSIONS Nonrandom assignment limits comparisons between antidepressants and anti-psychotics in this study. However, with follow-up, a number of adolescents meeting criteria for prodromal schizophrenia were successfully treated with antidepressants. At present, a substantial number of false positives among the antidepressant-treated subgroup cannot be ruled out. However, the findings suggest that, in some cases, it might be preferable to begin treatment with antidepressants and progress to antipsychotics once symptoms intensify, since adherence to the latter is difficult to maintain.

Differentiation in the Preonset Phases of Schizophrenia and Mood Disorders: Evidence in Support of a Bipolar Mania Prodrome

Abstract: Objective: The presence and specificity of a bipolar prodrome remains questioned. We aimed to characterize the prodrome prior to a first psychotic and nonpsychotic mania and to examine the phenotypic proximity to the schizophrenia prodrome. Methods: Using a semi-structured interview, the Bipolar Prodrome Symptom Scale-Retrospective, information regarding the mania prodrome was collected from youth with a research diagnosis of bipolar I disorder and onset before 19 years of age, and/or their caregivers. Only newly emerging, at least moderately severe, symptoms were analyzed. Prodromal characteristics were compared between patients with and without subsequent psychotic mania and with published bipolar and schizophrenia prodrome data. Results: In 52 youth (age at first mania: 13.4 ± 3.3 years), the prodrome onset was predominantly “insidious” (>1 year, 51.9%) or “subacute” (1–12 months, 44.2%), while “acute” presentations (<1 month, 3.8%) were rare. The prodrome duration was similar in patients with (1.7 ± 1.8 years, n = 34) and without (1.9 ± 1.5 years, n = 18) subsequent psychotic mania (P = .70). Attenuated positive symptoms emerging late in the prodrome and increased energy/goal-directed activity were significantly more common in patients with later psychotic mania. Mania and schizophrenia prodrome characteristics overlapped considerably. However, subsyndromal unusual ideas were significantly more likely part of the schizophrenia prodrome, while obsessions/compulsions, suicidality, difficulty thinking/communicating clearly, depressed mood, decreased concentration/memory, tiredness/lack of energy, mood lability, and physical agitation were more likely part of the mania prodrome. Conclusions: A lengthy and symptomatic prodrome makes clinical high-risk research a feasible goal for bipolar disorder. The phenotypic overlap with the schizophrenia prodrome necessitates the concurrent study of both illness prodromes.

Early identification and high-risk strategies for bipolar disorder

Abstract: Correll CU, Penzner JB, Lencz T, Auther A, Smith CW, Malhotra AK, Kane JM, Cornblatt BA. Early identification and high-risk strategies for bipolar disorder. Bipolar Disord 2007: 9: 324-338. © Blackwell Munksgaard, 2007 Objectives: To describe and compare the relative merits of different identification strategies for individuals at risk for bipolar disorder (BPD). Methods: Selective review of data that support early identification in BPD, with a particular focus on emerging clinical high-risk strategies. Results: Early detection of individuals at risk for BPD can utilize genetic, endophenotypic and clinical methods. Most published work focuses on genetic familial endophenotypic risk markers for BPD. However, despite encouraging results, problems with specificity and sensitivity limit the application of these data to early prevention programs. In addition, offspring studies of BPD patients systematically exclude the majority of subjects without a first-degree bipolar relative. On the other hand, emerging work in the clinical-high-risk arena has already produced encouraging results. Although still preliminary, the identification of individuals in subsyndromal or attenuated symptom 'prodromal' stages of BPD seems to be an under-researched area that holds considerable promise deserving increased attention. Required next steps include the development of rating tools for attenuated and subsyndromal manic and depressive symptoms and of prodromal criteria that will allow prodromal symptomatology to be systematically studied in patients with recent-onset bipolar, as well as in prospective population-based phenomenology trials and attenuated symptom-based high-risk studies. Conclusions: Given the current limitations of each early identification method, combining clinical, endophenotypic and genetic strategies will increase prediction accuracy. Since reliable biological markers for BPD have not been established and since most patients with BPD lack a first-degree relative with this disorder, clinical high-risk approaches have great potential to inform early identification and intervention programs.

Editor's Introduction: The Empirical Status of the Ultra High-Risk (Prodromal) Research Paradigm

Abstract: Given the growth of prodromal research in the past 15 years, the time seems right for assessing whether the ultra high-risk (UHR) research paradigm has delivered on its promise as an approach to identification of individuals at risk for imminent onset of psychosis and as a platform for studies assessing protective benefits of early interventions and for elucidating predictive markers. As demonstrated by the 8 articles on this theme in the present issue, the empirical basis of the prodromal research area has advanced significantly. While there is a lower risk for transition to psychosis in recent studies compared with initial studies, most recent studies still show a 30%-35% risk for psychosis within 1-2 years of follow-up, a rate that is substantially higher than the incidence rate of psychosis among transition age youth in the general population. Moreover, the means with which to improve this predictive equation is rapidly developing, enabled by the collaborative integration of data across multiple sites, the employment of multivariate risk algorithms, and a longitudinal perspective on symptoms, cognition, and functioning. All the initial intervention studies have produced encouraging findings, albeit with small sample sizes and relatively large attrition rates. Nevertheless, the findings in this issue, together with others like them appearing at an increasing rate in the world literature, indicate that the prodromal research area is increasing in maturity and sophistication, providing a useful heuristic for early detection and intervention in those at risk for psychosis.

Neuroprotection in emerging psychotic disorders

Abstract: Aim: The emerging phase of psychotic disorders is pleomorphic and fluctuates in presentation. Hence, from a clinical perspective, treatment modalities are often unclear. This paper investigates the rational and potential use of neuroprotective agents in emerging psychotic disorders. Methods: Medline databases were searched from 1966 to 2006 followed by the cross-checking of references using following keywords: neuroprotection, apoptosis, natural cell death, neurodevelopment, plasticity, neurogenesis, combined with brain and schizophrenia. Results: Agents such as atypical antipsychotics, antidepressants, omega-3 fatty acids, modulators of glutamateric neurotransmission (e.g. ampakines, glycine, memantine), erythropoietin, N-acetylcysteine, COX-2 inhibitors or antioxidants have neuroprotective (anti-apoptotic) properties and may therefore be able to protect brain maturational processes disturbed in emerging psychotic disorders. Clinical trials suggest that atypical antipsychotics, antidepressants, omega-3 fatty acids and low-dose lithium as sole treatments were able to improve symptoms and functioning, and delay or in some cases even prevent the onset of frank psychosis. Initially these substances have been chosen because they have been used either as sole or augmentation treatments in established psychotic disorders. However, chronicity and already effective treatments may overshadow their potential clinical use in emerging (prodromal) psychosis. Conclusion: Neuroprotection as a new treatment paradigm for at-risk mental states seems to be promising and pilot data are suggestive that more benign interventions may already be sufficient to delay or even prevent the onset of frank psychosis. A coordinated research effort will be necessary to address the question which agents should be used under which circumstances. (PsycINFO Database Record (c) 2008 APA, all rights reserved) (journal abstract).

Review Article Neuroprotection in emerging psychotic disorders

Abstract: Aim: The emerging phase of psychotic disorders is pleomorphic and fluctuates in presentation. Hence, from a clinical perspective, treatment modalities are often unclear. This paper investigates the rational and potential use of neuroprotective agents in emerging psychotic disorders. Methods: Medline databases were searched from 1966 to 2006 followed by the cross-checking of references using following keywords: neuroprotection, apoptosis, natural cell death, neurodevelopment, plasticity, neurogenesis, combined with brain and schizophrenia.