Publications (167) View all
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Article: Identification of clinically meaningful relationships among cognition, functionality, and symptoms in subjects with schizophrenia or schizoaffective disorder.
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ABSTRACT: INTRODUCTION: Cognitive impairment in schizophrenia and schizoaffective disorder is a major determinant of disability. This study explored the relationships among cognitive functioning, clinical symptoms, overall functionality, and demographic characteristics. METHODS: This was a post hoc analysis of a 52-week, prospective, randomized, double-blind study (N=323) comparing 2 doses of risperidone long-acting injectable (RLAI) in stable subjects with schizophrenia or schizoaffective disorder. Cognitive evaluations were performed and standardized using a healthy age- and sex-matched comparison group. Simple and multiple regression models were used to identify relationships among neurocognitive composite scores (NCS), clinical symptom end points (Positive and Negative Syndrome Scale [PANSS] total and factor scores), overall functionality (Personal and Social Performance [PSP] score), and demographics. RESULTS: A simple regression model identified significant relationships between the NCS at end point and PANSS total score, PANSS disorganized thoughts factor score, functioning (PSP) and age. A 1-point decrease on PANSS total score and PANSS disorganized thoughts factor score corresponded to an increase in NCS of 0.126-point, and 0.81-point increases, respectively. A 1-point increase on the PSP corresponded to a 0.186-point increase in the NCS T-score. Among the demographic variables, only age correlated significantly with cognition (10-year increase in age corresponded to 1.1-point decrease in NCS T-score) in a multiple regression model. CONCLUSION: Improved cognition was associated with beneficial changes in functional status and clinical symptoms (particularly disorganization symptoms) in subjects with schizophrenia/schizoaffective disorder. Older subjects showed less overall cognitive improvement. Improved cognitive and functional outcome is correlated with symptom improvements in RLAI-treated patients with schizophrenia.Biological Psychiatry 12/2012; · 8.28 Impact Factor -
Article: A preliminary, randomized, double-blind, placebo-controlled trial of l-carnosine to improve cognition in schizophrenia.
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ABSTRACT: BACKGROUND: Targeting glutamatergic dysfunction provides an exciting opportunity to improve cognitive impairment in schizophrenia. One treatment approach has targeted inadequate antioxidant defenses at glutamatergic synapses. Animal and human data suggest NMDA antagonists worsen executive cognitive controls - e.g. increase perseverative responses and impair set-shifting. We conducted a preliminary study to test the hypothesis that l-carnosine, an antioxidant and anti-glycation agent which is co-localized and released with glutamate would improve executive dysfunction, a cognitive domain associated with glutamate. METHODS: Seventy-five symptomatically stable adults with chronic schizophrenia were randomly assigned to l-carnosine as adjunctive treatment (2g/day) or a matched placebo in a double-blind manner for 3months. Cognitive domains (executive dysfunction, memory, attention and motor speed) were assessed using a computerized battery at baseline, 4 and 12weeks, along with psychopathology ratings and safety parameters. RESULTS: The l-carnosine group performed significantly faster on non-reversal condition trials of the set-shifting test compared with placebo but reversal reaction times and errors were not significantly different between treatments. On the strategic target detection test, the l-carnosine group displayed significantly improved strategic efficiency and made fewer perseverative errors compared with placebo. Other cognitive tests showed no significant differences between treatments. Psychopathology scores remained stable. The carnosine group reported more adverse events (30%) compared with the placebo group (14%). Laboratory indices remained within acceptable ranges. CONCLUSIONS: These preliminary findings suggest that l-carnosine merits further consideration as adjunctive treatment to improve executive dysfunction in persons with schizophrenia.Biological Psychiatry 10/2012; · 8.28 Impact Factor -
Article: Functional polymorphisms in dopamine-related genes: effect on neurocognitive functioning in HIV+ adults.
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ABSTRACT: Dopaminergic dysfunction is a putative mechanism underlying HIV-associated neurocognitive disorders. Dopamine transporter (DAT), brain-derived neurotrophic factor (BDNF), and catechol-O-methyltransferase (COMT) have been specifically implicated. We report analyses examining the main effects of functional polymorphisms within dopamine-modulating genes, as well as their interactive effects with disease severity, upon neurocognitive functioning in HIV+ adults. A total of 184 HIV+ adults were included in the analysis. Three polymorphisms were examined within dopamine-modulating genes: COMT val158met, BDNF val66met, and the DAT 3' variable number tandem repeat. Separate hierarchical regression analyses for five neurocognitive domains (working memory, processing speed, learning, memory, motor) were conducted. Predictor variables were age, ethnicity, gender, education, CD4+ T-cell count, current depression, genotype, and an interaction term capturing genotype and disease severity (CD4). None of the polymorphisms or HIV disease variables significantly improved the hierarchical regression models. Younger age, higher education, and Caucasian ethnicity were almost invariably associated with better functioning across all five cognitive domains. A trend was noted for current depression as a predictor of motor and learning ability. This study did not find evidence to support direct or interactive effects of dopamine-related genes and HIV disease severity on neurocognitive functioning.Journal of Clinical and Experimental Neuropsychology 11/2011; 34(1):78-91. · 2.13 Impact Factor -
Article: Bifactor and item response theory analyses of interviewer report scales of cognitive impairment in schizophrenia.
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ABSTRACT: A psychometric analysis of 2 interview-based measures of cognitive deficits was conducted: the 21-item Clinical Global Impression of Cognition in Schizophrenia (CGI-CogS; Ventura et al., 2008), and the 20-item Schizophrenia Cognition Rating Scale (SCoRS; Keefe et al., 2006), which were administered on 2 occasions to a sample of people with schizophrenia. Traditional psychometrics, bifactor analysis, and item response theory methods were used to explore item functioning and dimensionality and to compare instruments. Despite containing similar item content, responses to the CGI-CogS demonstrated superior psychometric properties (e.g., higher item intercorrelations, better spread of ratings across response categories) relative to the SCoRS. The authors argue that these differences arise mainly from the differential use of prompts and how the items are phrased and scored. Bifactor analysis demonstrated that although both measures capture a broad range of cognitive functioning (e.g., working memory, social cognition), the common variance on each is overwhelmingly explained by a single general factor. Item response theory analyses of the combined pool of 41 items showed that measurement precision is peaked in the mild to moderate range of cognitive impairment. Finally, simulated adaptive testing revealed that only about 10 to 12 items are necessary to achieve latent trait level estimates with reasonably small standard errors for most individuals. This suggests that these interview-based measures of cognitive deficits could be shortened without loss of measurement precision.Psychological Assessment 03/2011; 23(1):245-61. · 2.99 Impact Factor -
Article: The neuropsychology of schizophrenia circa 2009.
Neuropsychology Review 09/2009; 19(3):277-9. · 6.62 Impact Factor
