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Leshner A.F.,VA Greater Los Angeles Healthcare System | Tom S.R.,VA Greater Los Angeles Healthcare System | Kern R.S.,University of California at Los Angeles | Kern R.S.,VISN 22 Mental Illness Research
Psychiatry Research | Year: 2013

Compensatory approaches to cognitive rehabilitation in schizophrenia aim to improve functioning by bypassing or compensating for impaired areas of cognition. At present, there is little empirical evidence that these approaches actually compensate for neurocognitive impairments in improving community functioning. This study examined the effects of errorless learning (EL), a compensatory cognitive rehabilitation approach, on social problem solving ability in schizophrenia. The study included 60 outpatients who met DSM-IV criteria for schizophrenia or schizoaffective disorder. Participants received a baseline battery to assess explicit and implicit memory functioning. Participants were stratified according to gender and level of memory functioning and then randomized to EL or symptom management training. Training was conducted over two days lasting a total of 6. h for each group. Assessment of social problem-solving ability, using the Assessment of Interpersonal Problem Solving Skills (AIPSS), was conducted after completion of training and at a 3-month follow-up without further intervention. Results from hierarchical multiple regression and analysis of covariance each supported the compensatory effects of training. These findings indicate that EL facilitates learning of new skills across varying levels of memory impairment. Future efforts may aim to explore the specific neurocognitive mechanisms involved in EL. © 2012. Source

McCleery A.,Semel Institute for Neuroscience and Human Behavior | Ventura J.,Semel Institute for Neuroscience and Human Behavior | Kern R.S.,Semel Institute for Neuroscience and Human Behavior | Kern R.S.,VISN 22 Mental Illness Research | And 7 more authors.
Schizophrenia Research | Year: 2014

Background: Although many studies have assessed cognitive functioning in first-episode schizophrenia (FESz), the pattern and severity of impairment across cognitive domains remain unclear. Moreover, few studies have directly compared the pattern of cognitive performance between FESz and chronic schizophrenia (CSz). In this study we examined the cognitive impairment profile in FESz using a standardized neurocognitive battery (MATRICS Consensus Cognitive Battery; MCCB). Methods: MCCB data were compared from 105 FESz patients, 176 CSz patients and 300 non-psychiatric (NP) participants. Mixed model analysis evaluated group differences in MCCB profiles and relative strengths and weaknesses in the MCCB profiles of patients. Clinical implications of MCCB performance were also examined; we compared the proportion of participants from each group who exhibited clinically-significant global cognitive impairment based on the MCCB Overall Composite score. Results: FESz and CSz showed impaired performance across all MCCB domains relative to NP. With the exception of relative preservation of working memory and social cognition in FESz, the MCCB domain scores were similar in FESz and CSz. The distribution of impairment on the Overall Composite score did not significantly differ between FESz and CSz; compared to NP, both patient groups were overrepresented in moderate and severe impairment categories. Conclusion: The pattern, magnitude, and distribution of severity of impairment in FESz were similar to that observed in CSz. However, early in the illness, there may be relative sparing of working memory and social cognition. © 2014 Elsevier B.V. Source

Reddy L.F.,VISN 22 Mental Illness Research | Reddy L.F.,University of California at Los Angeles | Horan W.P.,VISN 22 Mental Illness Research | Horan W.P.,University of California at Los Angeles | And 14 more authors.
Schizophrenia Bulletin | Year: 2015

Impairments in willingness to exert effort contribute to the motivational deficits characteristic of the negative symptoms of schizophrenia. The current study evaluated the psychometric properties of 5 new or adapted paradigms to determine their suitability for use in clinical trials of schizophrenia. This study included 94 clinically stable participants with schizophrenia and 40 healthy controls. The effort-based decision-making battery was administered twice to the schizophrenia group (baseline, 4-week retest) and once to the control group. The 5 paradigms included 1 that assesses cognitive effort, 1 perceptual effort, and 3 that assess physical effort. Each paradigm was evaluated on (1) patient vs healthy control group differences, (2) test-retest reliability, (3) utility as a repeated measure (ie, practice effects), and (4) tolerability. The 5 paradigms showed varying psychometric strengths and weaknesses. The Effort Expenditure for Rewards Task showed the best reliability and utility as a repeated measure, while the Grip Effort Task had significant patient-control group differences, and superior tolerability and administration duration. The other paradigms showed weaker psychometric characteristics in their current forms. These findings highlight challenges in adapting effort and motivation paradigms for use in clinical trials. © 2015, Oxford University Press. All rights reserved. Source

Greenwood T.A.,University of California at San Diego | Light G.A.,University of California at San Diego | Light G.A.,VISN 22 Mental Illness Research | Swerdlow N.R.,University of California at San Diego | And 3 more authors.
PLoS ONE | Year: 2012

While it is clear that schizophrenia is highly heritable, the genetic basis of this heritability is complex. Human genetic, brain imaging, and model organism studies have met with only modest gains. A complementary research tactic is to evaluate the genetic substrates of quantitative endophenotypes with demonstrated deficits in schizophrenia patients. We used an Illumina custom 1,536-SNP array to interrogate 94 functionally relevant candidate genes for schizophrenia and evaluate association with both the qualitative diagnosis of schizophrenia and quantitative endophenotypes for schizophrenia. Subjects included 219 schizophrenia patients and normal comparison subjects of European ancestry and 76 schizophrenia patients and normal comparison subjects of African ancestry, all ascertained by the UCSD Schizophrenia Research Program. Six neurophysiological and neurocognitive endophenotype test paradigms were assessed: prepulse inhibition (PPI), P50 suppression, the antisaccade oculomotor task, the Letter-Number Span Test, the California Verbal Learning Test-II, and the Wisconsin Card Sorting Test-64 Card Version. These endophenotype test paradigms yielded six primary endophenotypes with prior evidence of heritability and demonstrated schizophrenia-related impairments, as well as eight secondary measures investigated as candidate endophenotypes. Schizophrenia patients showed significant deficits on ten of the endophenotypic measures, replicating prior studies and facilitating genetic analyses of these phenotypes. A total of 38 genes were found to be associated with at least one endophenotypic measure or schizophrenia with an empirical p-value<0.01. Many of these genes have been shown to interact on a molecular level, and eleven genes displayed evidence for pleiotropy, revealing associations with three or more endophenotypic measures. Among these genes were ERBB4 and NRG1, providing further support for a role of these genes in schizophrenia susceptibility. The observation of extensive pleiotropy for some genes and singular associations for others in our data may suggest both converging and independent genetic (and neural) pathways mediating schizophrenia risk and pathogenesis. © 2012 Greenwood et al. Source

Lombardo M.V.,University of Cyprus | Lombardo M.V.,University of Cambridge | Pierce K.,University of California at San Diego | Eyler L.T.,University of California at San Diego | And 6 more authors.
Neuron | Year: 2015

Autism (ASD) is vastly heterogeneous, particularly in early language development. While ASD language trajectories in the first years of life are highly unstable, by early childhood these trajectories stabilize and arepredictive of longer-term outcome. Early neural substrates that predict/precede such outcomes are largely unknown, but could have considerable translational and clinical impact. Pre-diagnosis fMRI response to speech in ASD toddlers with relatively good language outcome was highly similar to non-ASD comparison groups and robustly recruited language-sensitive superior temporal cortices. In contrast, language-sensitive superior temporal cortices were hypoactive in ASD toddlers with poor language outcome. Brain-behavioral relationships were atypically reversed in ASD, and a multimodal combination of pre-diagnostic clinical behavioral measures and speech-related fMRI response showed the most promise as an ASD prognosis classifier. Thus, before ASD diagnoses and outcome become clinically clear, distinct functional neuroimaging phenotypes are already present that can shed insight on an ASD toddler's later outcome. © 2015 Elsevier Inc. Source

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