VISN 22 Mental Illness Research

Los Angeles, CA, United States

VISN 22 Mental Illness Research

Los Angeles, CA, United States
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Kern R.S.,University of California at Los Angeles | Kern R.S.,VISN 22 Mental Illness Research | Kern R.S.,Greater Los Angeles Healthcare Center | Penn D.L.,University of North Carolina at Chapel Hill | And 9 more authors.
Schizophrenia Bulletin | Year: 2013

The psychometric properties of 4 paradigms adapted from the social neuroscience literature were evaluated to determine their suitability for use in clinical trials of schizophrenia. This 2-site study (University of California, Los Angeles and University of North Carolina) included 173 clinically stable schizophrenia outpatients and 88 healthy controls. The social cognition battery was administered twice to the schizophrenia group (baseline, 4-week retest) and once to the control group. The 4 paradigms included 2 that assess perception of nonverbal social and action cues (basic biological motion and emotion in biological motion) and 2 that involve higher level inferences about self and others' mental states (self-referential memory and empathic accuracy). Each paradigm was evaluated on (1) patient vs healthy control group differences, (2) test-retest reliability, (3) utility as a repeated measure, and (4) tolerability. Of the 4 paradigms, empathic accuracy demonstrated the strongest characteristics, including large between-group differences, adequate test-retest reliability (.72), negligible practice effects, and good tolerability ratings. The other paradigms showed weaker psychometric characteristics in their current forms. These findings highlight challenges in adapting social neuroscience paradigms for use in clinical trials. © 2013 The Author 2013.


Kirkpatrick B.,Texas A&M University | Kirkpatrick B.,Scott and White Healthcare | Strauss G.P.,University of Maryland, Baltimore | Nguyen L.,Georgia Regents University | And 7 more authors.
Schizophrenia Bulletin | Year: 2011

The participants in the NIMH-MATRICS Consensus Development Conference on Negative Symptoms recommended that an instrument be developed that measured blunted affect, alogia, asociality, anhedonia, and avolition. The Brief Negative Symptom Scale (BNSS) is a 13-item instrument designed for clinical trials and other studies that measures these 5 domains. The interrater, test-retest, and internal consistency of the instrument were strong, with respective intraclass correlation coefficients of 0.93 for the BNSS total score and values of 0.89-0.95 for individual subscales. Comparisons with positive symptoms and other negative symptom instruments supported the discriminant and concurrent validity of the instrument. © The Author 2011. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.


Ventura J.,University of California at Los Angeles | Tom S.R.,VISN 22 Mental Illness Research | Jetton C.,VISN 22 Mental Illness Research | Kern R.S.,University of California at Los Angeles | Kern R.S.,VISN 22 Mental Illness Research
Schizophrenia Research | Year: 2013

Background: Neurocognition in general, and memory functioning in particular, as well as symptoms have all been shown to be related to social problem solving (SPS) in schizophrenia. However, few studies have directly compared the relative contribution of neurocognition vs. psychiatric symptoms to the components of SPS. Method: Sixty outpatients (aged 21-65) who met DSM-IV criteria for schizophrenia or schizoaffective disorder were administered a broad battery of memory tests and assessed for severity of positive and negative symptoms as part of a baseline assessment of a study of psychiatric rehabilitation. Multiple regression analyses were used to examine the contribution of memory functioning vs. symptoms on receiving, processing, and sending skill areas of social problem solving ability. Results: An index of verbal learning was the strongest predictor of processing skills whereas negative symptoms were the strongest predictor of sending skills. Positive symptoms were not related to any of the three skill areas of social problem solving. Conclusions: Memory functioning and psychiatric symptoms differentially predict selected areas of social problem solving ability in persons with schizophrenia. Consistent with other reports, positive symptoms were not related to social problem solving. Consideration of both neurocognition and negative symptoms may be important to the development of rehabilitation interventions in this area of functioning. © 2012 Elsevier B.V.


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.


Davis M.C.,VISN 22 Mental Illness Research | Davis M.C.,University of California at Los Angeles | Horan W.P.,VISN 22 Mental Illness Research | Marder S.R.,VISN 22 Mental Illness Research | Marder S.R.,University of California at Los Angeles
European Neuropsychopharmacology | Year: 2014

The past decade has witnessed a resurgence of interest in the development of novel pharmacological agents to treat the negative symptoms of schizophrenia. This review provides an overview of pharmacological approaches that have been evaluated as potential treatments and describes the emergence of several promising new approaches. First, we briefly describe recent methodological developments, including consensus-based clinical trial guidelines for patient selection criteria, symptom assessment, and trial duration. Next, we overview mono- and adjunctive-therapies that have been evaluated, including first- and second-generation antipsychotics, antidepressants, psychostimulants, molecules targeting cholinergic and glutamatergic systems, and hormones. We highlight the most promising pharmacological agents on the horizon, including glycine transporter-1 inhibitors, α7-nicotinic receptor positive allosteric modulators, and oxytocin, as well as non-pharmacological electromagnetic stimulation approaches. Further investigations, using optimal clinical trial design, hold considerable promise for discovering effective treatments for these functionally disabling symptoms in the near future. © 2013.


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.


Jahshan C.,VISN 22 Mental Illness Research | Wynn J.K.,VISN 22 Mental Illness Research | Wynn J.K.,University of California at Los Angeles | Breitmeyer B.G.,University of Houston | And 2 more authors.
Journal of Psychiatric Research | Year: 2012

Deficits in visual processing are well established in schizophrenia. However, there is conflicting evidence about whether these deficits start before the formation of percepts because visual processing studies in schizophrenia have typically examined the processing of consciously registered stimuli. In this study, we used nonconscious color priming to evaluate the very early visual processing stages in schizophrenia. Nonconscious and conscious color priming was assessed in 148 schizophrenia patients and 54 healthy control subjects. In both conditions, subjects identified the color of a ring preceded by a disk (prime) in the same color (congruent) or a different color (incongruent). The ring rendered the disk invisible in the nonconscious condition (SOA of 62.5 ms) or did not mask the disk (SOA of 200 ms) in the conscious condition. Schizophrenia patients exhibited a color priming effect (longer reaction times in the incongruent vs. congruent trials) that was similar to healthy controls in both the nonconscious and conscious priming conditions. Healthy controls had a significantly larger priming effect in the nonconscious vs. conscious condition, but patients did not show a significant difference in priming effects between the two conditions. Our results indicate that schizophrenia patients do not have deficits at the nonconscious, pre-perceptual stages of visual processing, suggesting that the feed forward sweep of information processing (from retina to V1) might be intact in schizophrenia. These results imply that the well-documented visual processing deficits in this illness likely occur at later, percept-dependent stages of processing. © 2012.


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.


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 4 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.


PubMed | VISN 22 Mental Illness Research and University of California at San Diego
Type: | Journal: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology | Year: 2017

Computerized cognitive training is gaining empirical support for use in the treatment of schizophrenia (SZ). While cognitive training is efficacious for SZ at a group level when delivered in sufficiently intensive doses (eg, 30-50h), there is variability in individual patient response. The identification of biomarkers sensitive to the neural systems engaged by cognitive training interventions early in the course of treatment could facilitate personalized assignment to treatment. This proof-of-concept study was conducted to determine whether mismatch negativity (MMN), an event-related potential index of auditory sensory discrimination associated with cognitive and psychosocial functioning, would predict gains in auditory perceptual learning and exhibit malleability after initial exposure to the early stages of auditory cognitive training in SZ. MMN was assessed in N=28 SZ patients immediately before and after completing 1hr of a speeded time-order judgment task of two successive frequency modulated sweeps (Posit Science Sound Sweeps exercise). All SZ patients exhibited the expected improvements in auditory perceptual learning over the 1hr training period (p<0.001), consistent with previous results. Larger MMN amplitudes recorded both before and after the training exercises were associated with greater gains in auditory perceptual learning (r=-0.5, and r=-0.67, respectively, ps<0.01). Significant pre-vs post-training MMN amplitude reduction was also observed (p<0.02). MMN is a sensitive index of the neural systems engaged in a single session of auditory cognitive training in SZ. These findings encourage future trials of MMN as a biomarker for individual assignment, prediction, and/or monitoring of patient response to pro-cognitive interventions, including auditory cognitive training in SZ.Neuropsychopharmacology accepted article preview online, 31 January 2017. doi:10.1038/npp.2017.25.

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