Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia II: Developing Imaging Biomarkers to Enhance Treatment Development for Schizophrenia and Related Disorders

Department of Psychiatry, University of California at Davis, Sacramento, California, USA.
Biological psychiatry (Impact Factor: 10.26). 07/2011; 70(1):7-12. DOI: 10.1016/j.biopsych.2011.01.041
Source: PubMed


The Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative, funded by an R13 from the National Institute of Mental Health, seeks to enhance translational research in treatment development for impaired cognition in schizophrenia by developing tools from cognitive neuroscience into useful measures of treatment effects on behavior and brain function. An initial series of meetings focused on the selection of a new set of tasks from cognitive neuroscience for the measurement of treatment effects on specific cognitive and neural systems. Subsequent validation and optimization studies are underway and a subset of validated measures with well-characterized psychometric properties will be generally available in 2011. This article describes results of the first meeting of the second phase of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia, which seeks to develop imaging biomarkers and improved animal models to enhance translational research. In this meeting, we considered issues related to the use of methods such as functional magnetic resonance imaging, electroencephalography, magnetoencephalography, and transcranial magnetic simulation as biomarkers for treatment development. We explored the biological nature of the signals measured by each method, their validity and reliability as measures of cognition-related neural activity, potential confounds related to drug effects on the signal of interest, and conceptual, methodological, and pragmatic issues related to their use in preclinical, first into human, and multicenter phase II and III studies. This overview article describes the background and goals of the meeting together with a summary of the major issues discussed in more detail in the accompanying articles appearing in this issue of Biological Psychiatry.

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    • "Disturbances of neurofunctional processing can be studied using both structural and functional imaging as well as neurophysiological measures such as EEG and event-related potentials (Javitt et al., 2008; Keshavan et al., 2008; Carter et al., 2011). To date, many research efforts in schizophrenia (SZ) have been devoted to the assessment of evoked responses extracted from EEG measures. "
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    ABSTRACT: Basic visual dysfunctions are commonly reported in schizophrenia; however their value as diagnostic tools remains uncertain. This study reports a novel electrophysiological approach using checkerboard visual evoked potentials (VEP). Sources of spectral resolution VEP-components C1, P1 and N1 were estimated by LORETA, and the band-effects (BSE) on these estimated sources were explored in each subject. BSEs were Z-transformed for each component and relationships with clinical variables were assessed. Clinical effects were evaluated by ROC-curves and predictive values. Forty-eight patients with schizophrenia (SZ) and 55 healthy controls participated in the study. For each of the 48 patients, the three VEP components were localized to both dorsal and ventral brain areas and also deviated from a normal distribution. P1 and N1 deviations were independent of treatment, illness chronicity or gender. Results from LORETA also suggest that deficits in thalamus, posterior cingulum, precuneus, superior parietal and medial occipitotemporal areas were associated with symptom severity. While positive symptoms were more strongly related to sensory processing deficits (P1), negative symptoms were more strongly related to perceptual processing dysfunction (N1). Clinical validation revealed positive and negative predictive values for correctly classifying SZ of 100% and 77%, respectively. Classification in an additional independent sample of 30 SZ corroborated these results. In summary, this novel approach revealed basic visual dysfunctions in all patients with schizophrenia, suggesting these visual dysfunctions represent a promising candidate as a biomarker for schizophrenia.
    Schizophrenia Research 08/2014; 159(1). DOI:10.1016/j.schres.2014.07.052 · 3.92 Impact Factor
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    • "Another popular method of assessment involves the use of biomarkers , which are biochemical, genetic, or molecular indicators (e.g., using neuroimaging, neurophysiological, or neuropsychological assessment) of a particular biological condition or process. Currently popular and fruitful areas for the use of biomarkers are in assessment and treatment planning for dementia, schizophrenia, and depression— for example, screening individuals atrisk for psychosis (kCarter et al., 2012; Klöppel et al., 2012; Luck et al., 2011). While neuroimaging and neurophysiological methods are popular, neurocognitive pattern recognition using traditional neuropsychological assessment measures also holds promise (Koutsouleris et al., 2012). "

    Multimethod assessment and treatment planning, 1st edited by C. J. Hopwood & R. F. Bornstein, 06/2014: chapter Multimethod assessment and treatment planning: pages 285-318; Guilford Press., ISBN: 978-1462516018
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    • "These models are then applied to psychiatric populations to identify biomarkers or endophenotypes that point to the mechanisms of attention , memory, and other higher cognitive processes underlying the behavioral phenotypes of psychiatric disorder. Biomarkers refer to characteristics that are measured objectively as an index of a pathogenic process or as a response to treatment (Carter et al., 2011), while endophenotypes refer to well-specified physiological or behavioral measures that occupy the terrain between disease symptoms (behavioral phenotypes) and risk genotypes (Insel & Cuthbert, 2009). The final step in the translational approach involves testing the biomarker as a mechanism of change in clinical trials. "
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    ABSTRACT: This study offers a developmentally sensitive conceptual understanding of trauma by viewing posttraumatic stress disorder (PTSD) through the lens of social cognition. First, we justify our focus on social cognition by examining the literature on problematic interpersonal relationships associated with PTSD. Next, we link impaired social cognition to the developmental compromise of mentalizing capacity in attachment relationships. We then integrate the diverse research literature into a social‐cognitive model of the development of PTSD. We finally conclude by suggesting directions for future research, as it might be shaped by trends in social‐cognitive neuroscience.
    Clinical Psychology Science and Practice 09/2012; 19(3). DOI:10.1111/cpsp.12002 · 2.92 Impact Factor
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