Carter CS, Barch DM, Buchanan RW, Bullmore E, Krystal JH, Cohen J et al. Identifying cognitive mechanisms targeted for treatment development in schizophrenia: an overview of the first meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia Initiative. Biol Psychiatry 64: 4-10

Department of Psychiatry, University of California, Davis, CA 95817, USA.
Biological psychiatry (Impact Factor: 10.26). 08/2008; 64(1):4-10. DOI: 10.1016/j.biopsych.2008.03.020
Source: PubMed


This overview describes the generation and development of the ideas that led to the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative. It also describes the organization, process, and products of the first meeting. The CNTRICS initiative involves a series of three conferences that will systematically address barriers to translating paradigms developed in the basic animal and human cognitive neuroscience fields for use in translational research aimed at developing novel treatments for cognitive impairments in schizophrenia. The articles in this special section report on the results of the first conference, which used a criterion-based consensus-building process to develop a set of cognitive constructs to be targeted for translation efforts.

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Available from: Edward T Bullmore
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    • "The psychiatric comparison groups allow us to examine memory impairment in schizophrenia in the context of individuals who are hypothesized to share genetic risk architecture with schizophrenia. A large reference sample of community volunteers (n = 1101) was collected to provide robust estimation of the normative distributions of performance on all measures, which included both established neuropsychological tasks and experimental tasks designed to isolate theoretically separable aspects of working and episodic memory functioning (Carter et al., 2008). "
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    ABSTRACT: Schizophrenia patients exhibit impaired working and episodic memory, but this may represent generalized impairment across memory modalities or performance deficits restricted to particular memory systems in subgroups of patients. Furthermore, it is unclear whether deficits are unique from those associated with other disorders. Healthy controls (n=1101) and patients with schizophrenia (n=58), bipolar disorder (n=49) and attention-deficit-hyperactivity-disorder (n=46) performed 18 tasks addressing primarily verbal and spatial episodic and working memory. Effect sizes for group contrasts were compared across tasks and the consistency of subjects' distributional positions across memory domains was measured. Schizophrenia patients performed poorly relative to the other groups on every test. While low to moderate correlation was found between memory domains (r=.320), supporting modularity of these systems, there was limited agreement between measures regarding each individual's task performance (ICC=.292) and in identifying those individuals falling into the lowest quintile (kappa=0.259). A general ability factor accounted for nearly all of the group differences in performance and agreement across measures in classifying low performers. Pathophysiological processes involved in schizophrenia appear to act primarily on general abilities required in all tasks rather than on specific abilities within different memory domains and modalities. These effects represent a general shift in the overall distribution of general ability (i.e., each case functioning at a lower level than they would have if not for the illness), rather than presence of a generally low-performing subgroup of patients. There is little evidence that memory impairments in schizophrenia are shared with bipolar disorder and ADHD. Copyright © 2015 Elsevier B.V. All rights reserved.
    Full-text · Article · Aug 2015 · Schizophrenia Research
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    • "This may be particularly true in studying the neurobiology of cognitive deficits, which remain the most difficult symptom cluster to treat in SZ yet hold the most promise for enhancing functional outcome (Green et al., 2000; Ibrahim and Tamminga, 2012). Indeed, the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative (Barch et al., 2008; Carter et al., 2008) has placed an emphasis on cognition as a core symptom of SZ, with the goal of assessing specific cognitive processes and their associated neural/psychological mechanisms in both animal models and humans in an effort to develop novel intervention strategies. We recently introduced chronic elevations of kynurenic acid (KYNA) as a naturalistic and translationally valid approach to experimentally study cognitive impairments seen in SZ. "
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    ABSTRACT: The levels of kynurenic acid (KYNA), an endogenous negative modulator of alpha7 nicotinic acetylcholine receptors (α7nAChRs), are elevated in the brains of patients with schizophrenia (SZ). We reported that increases of brain KYNA in rats, through dietary exposure to its precursor kynurenine from embryonic day (ED)15 to postnatal day (PD) 21, result in neurochemical and cognitive deficits in adulthood. The present experiments focused on the effects of prenatal exposure to elevated kynurenine on measures of prefrontal excitability known to be impaired in SZ. Pregnant dams were fed a mash containing kynurenine (100 mg/day; progeny = EKYNs) from ED15 until ED22. Controls were fed an unadulterated mash (progeny = ECONs). The dietary loading procedure elevated maternal and fetal plasma kynurenine (2223% and 693% above controls, respectively) and increased fetal KYNA (forebrain; 500% above controls) on ED21. Elevations in forebrain KYNA disappeared after termination of the loading (PD2), but KYNA levels in the prefrontal cortex (PFC) were unexpectedly increased again when measured in adults (PD56-80; 75% above controls). We also observed changes in several markers of prefrontal excitability, including expression of the α7nAChR (22% and 17% reductions at PD2 and PD56-80), expression of mGluR2 (31% and 24% reductions at ED21 and PD56-80), dendritic spine density (11-14% decrease at PD56-80), subsensitive mesolimbic stimulation of glutamate release in PFC, and reversal/extra-dimensional shift deficits in the prefrontally-mediated set-shifting task. These results highlight the deleterious impact of elevated KYNA levels during sensitive periods of early development, which model the pathophysiological and cognitive deficits seen in SZ. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Full-text · Article · Nov 2014 · Neuropharmacology
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    • "Analysis—To examine effects of cognitive control on DLPFC activation, we conducted an a priori region-of-interest (ROI) analysis with a functionally defined DLPFC ROI [Talairach coordinates Right: x=41, y=18, z=28, Left: x= −41, y=18, z=28, 36 voxels; (MacDonald et al., 2000)], previously shown to identify group differences under high cognitive control conditions in multiple FE studies (MacDonald and Carter, 2003; Snitz et al., 2005; Yoon et al., 2008). Beta weights for correct trials only were extracted from Cue A and Cue B contrast images separately. "
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    ABSTRACT: While structural abnormalities of the dorsolateral prefrontal cortex (DLPFC) may pre-date and predict psychosis onset, the relationships between functional deficits, cognitive and psychosocial impairments has yet to be explored in the at-risk period. An established measure of cognitive control (AXCPT) was administered to demographically matched clinical-high-risk (CHR; n=25), first-episode schizophrenia (FE; n=35), and healthy control (HC; n=35) participants during functional magnetic resonance imaging (fMRI) to investigate these relationships. CHR and FE individuals demonstrated impaired context processing and reduced DLPFC activation relative to HC individuals during increased cognitive control demands. FE and CHR individuals' ability to increase DLPFC activity in response to cognitive control demands was associated with better task performance. Task performance was also associated with severity of disorganization and poverty symptoms in FE participants. These findings support more extensive studies using fMRI to examine the clinical significance of prefrontal cortical functioning in the earliest stages of psychosis.
    Full-text · Article · Oct 2013
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