VA Desert Pacific Mental Illness Research

Los Angeles, CA, United States

VA Desert Pacific Mental Illness Research

Los Angeles, CA, United States

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Keefe R.S.E.,Duke University | Vinogradov S.,University of California at San Francisco | Medalia A.,Columbia University | Buckley P.F.,Georgia Regents University | And 14 more authors.
Journal of Clinical Psychiatry | Year: 2012

Background: The true benefit of pharmacologic intervention to improve cognition in schizophrenia may not be evident without regular cognitive enrichment. Clinical trials assessing the neurocognitive effects of new medications may require engagement in cognitive remediation exercises to stimulate the benefit potential. However, the feasibility of large-scale multisite studies using cognitive remediation at clinical trials sites has not been established. Method: 53 adult patients with DSM-IV schizophrenia from 9 university-affiliated sites were randomized to a cognitive remediation condition that included the Posit Science Brain Fitness auditory training program with weekly Neuropsychological and Educational Approach to Remediation (NEAR) "bridging groups" or a control condition of computer games and weekly healthy lifestyles groups. Patients were expected to complete 3 to 5 one-hour sessions weekly for 40 sessions or 12 weeks, whichever came first. The primary outcomes were feasibility results as measured by rate of enrollment, retention, and completion rate of primary outcome measures. The study was conducted from July 2009 through January 2010. Results: During a 3-month enrollment period, 53 (of a projected 54) patients were enrolled, and 41 (77%) met criteria for study completion. Thirty-one patients completed all 40 sessions, and all patients completed all primary outcome measures. Preliminary efficacy results indicated that, after 20 sessions, patients in the cognitive remediation condition demonstrated mean MATRICS Consensus Cognitive Battery composite score improvements that were 3.7 (95% CI, 0.05-7.34) T-score points greater than in patients in the computer-games control group (F1,46 = 4.16, P = .047). At the end of treatment, a trend favoring cognitive remediation was not statistically significant (F1,47 = 2.26, P = .14). Conclusion: Multisite clinical trials of cognitive remediation using the Posit Science Brain Fitness auditory training program with the NEAR method of weekly bridging groups at traditional clinical sites appear to be feasible. Trial Registration: ClinicalTrials.gov identifier: NCT00930150 © Copyright 2012 Physicians Postgraduate Press, Inc.


Arango C.,Complutense University of Madrid | Garibaldi G.,Hoffmann-La Roche | Marder S.R.,University of California at Los Angeles | Marder S.R.,VA Desert Pacific Mental Illness Research
Schizophrenia Research | Year: 2013

Clinical trials of pharmacological agents targeting negative symptoms in schizophrenia are reviewed. The focus is on trials that occurred in patients who were stable on an antipsychotic medication at entry to the trial. A small number of trials compared antipsychotics as monotherapy for negative symptoms. Although the data supporting amisulpride for negative symptoms is promising the trials have limitations and it is plausible that the advantages of amisulpride over placebo may result from effects on secondary negative symptoms. Among available agents, antidepressant medications may have effects in negative symptoms. Other promising agents include minocycline, glutamatergic agents, and alpha-7 nicotinic agents. More than 15 active trials are currently underway to evaluate new treatments for negative symptoms. © 2013.


Marder S.R.,University of California at Los Angeles | Marder S.R.,VA Desert Pacific Mental Illness Research | Alphs L.,Janssen Scientific Affairs LLC | Anghelescu I.-G.,Private Mental Hospital Dr Med Kurt Fontheim | And 23 more authors.
Schizophrenia Research | Year: 2013

A number of pharmacological agents for treating negative symptoms in schizophrenia are currently in development. Unresolved questions regarding the design of clinical trials in this area were discussed at an international meeting in Florence, Italy in April 2012. Participants included representatives from academia, the pharmaceutical industry, and the European Medicines Agency (EMA). Prior to the meeting, participants submitted key questions for debate and discussion. Responses to the questions guided the discussion during the meeting. The group reached agreement on a number of issues: (1) study subjects should be under the age of 65; (2) subjects should be excluded for symptoms of depression that do not overlap with negative symptoms; (3) functional measures should not be required as a co-primary in negative symptom trials; (4) information from informants should be included for ratings when available; (5) Phase 2 negative symptom trials should be 12. weeks and 26. weeks is preferred for Phase 3 trials; (6) prior to entry into a negative symptom study, subjects should demonstrate clinical stability for a period of 4 to 6. months by collection of retrospective information; and (7) prior to entry, the stability of negative and positive symptoms should be confirmed prospectively for four weeks or longer. The participants could not reach agreement on whether predominant or prominent negative symptoms should be required for study subjects. © 2013.


Davis M.C.,University of California at Los Angeles | Davis M.C.,VA Desert Pacific Mental Illness Research | Horan W.P.,University of California at Los Angeles | Horan W.P.,VA Desert Pacific Mental Illness Research | And 6 more authors.
Schizophrenia Research | Year: 2014

Individuals with schizophrenia often show substantial deficits in social cognitive abilities, which are strongly associated with social functioning. To advance our understanding of the genetic variation that is associated with social cognitive deficits in schizophrenia, we genotyped 74 schizophrenia outpatients who completed social cognitive performance measures assessing mentalizing, social perception, and emotional intelligence, as well as clinical symptoms. We assessed seven single nucleotide polymorphisms (SNPs) of the oxytocin receptor (OXTR) previously found to show replicable associations with socio-emotional processes. For one of the seven SNPs, rs2268493, the 'T' allele was significantly associated with poorer performance on a composite social cognition index, as well as specific tests of mentalizing and social perception. None of the SNPs were associated with clinical symptoms. Though the sample size is small, these findings provide initial support for the involvement of genetic variants of the OXTR in social cognitive impairments in schizophrenia. © 2014.


Hamilton A.B.,VA Desert Pacific Mental Illness Research | Hamilton A.B.,University of California at Los Angeles | Cohen A.N.,VA Desert Pacific Mental Illness Research | Cohen A.N.,University of California at Los Angeles | And 2 more authors.
Journal of General Internal Medicine | Year: 2010

Background: Implementing quality improvement efforts in clinics is challenging. Assessment of organizational "readiness" for change can set the stage for implementation by providing information regarding existing strengths and deficiencies, thereby increasing the chance of a successful improvement effort. This paper discusses organizational assessment in specialty mental health, in preparation for improving care for individuals with schizophrenia. OBJECTIVE: To assess organizational readiness for change in specialty mental health in order to facilitate locally tailored implementation strategies. DESIGN: EQUIP-2 is a site-level controlled trial at nine VA medical centers (four intervention, five control). Providers at all sites completed an organizational readiness for change (ORC) measure, and key stakeholders at the intervention sites completed a semi-structured interview at baseline. PARTICIPANTS: At the four intervention sites, 16 administrators and 43 clinical staff completed the ORC, and 38 key stakeholders were interviewed. MAIN RESULTS: The readiness domains of training needs, communication, and change were the domains with lower mean scores (i.e., potential deficiencies) ranging from a low of 23.8 to a high of 36.2 on a scale of 10-50, while staff attributes of growth and adaptability had higher mean scores (i.e., potential strengths) ranging from a low of 35.4 to a high of 41.1. Semi-structured interviews revealed that staff perceptions and experiences of change and decision-making are affected by larger structural factors such as change mandates from VA headquarters. CONCLUSIONS: Motivation for change, organizational climate, staff perceptions and beliefs, and prior experience with change efforts contribute to readiness for change in specialty mental health. Sites with less readiness for change may require more flexibility in the implementation of a quality improvement intervention. We suggest that uptake of evidence-based practices can be enhanced by tailoring implementation efforts to the strengths and deficiencies of the organizations that are implementing quality improvement changes. © 2009 Society of General Internal Medicine.


Velligan D.I.,University of Texas Health Science Center at San Antonio | Fredrick M.,University of Texas Health Science Center at San Antonio | Mintz J.,University of Texas Health Science Center at San Antonio | Li X.,University of Texas Health Science Center at San Antonio | And 9 more authors.
Schizophrenia Bulletin | Year: 2014

Objectives: The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative was designed to encourage the development of cognitive enhancing agents for schizophrenia. For a medication to receive this indication, regulatory agencies require evidence of improvement in both cognition and functional outcome. Functional capacity measures typically used in clinical trials as intermediate measures of functional outcome must be adapted to fit different cultural contexts for use internationally. We examined the psychometric properties of the MATRICS Functional Assessment Battery (MFAB), comprised of 2 subtests from the UCSD Performancebased Skills Assessment (UPSA) and one from the Test of Adaptive Behavior in Schizophrenia (TABS) that were rated by experts in a previous study to be the most appropriate functional capacity assessments across different cultural contexts. Method: Four sites in India administered the MFAB, a brief version of the UPSA, the MATRICS Cognitive Consensus Battery, measures of symptomatology, and a measure of global functional outcome to 141 individuals with schizophrenia at a baseline assessment and at 4 weeks later. Results: Test-retest reliability based on the intraclass correlation coefficient was significantly better for the UCSD Performance-Based Skills Assessment- Brief (UPSA-B). Pearson correlation coefficients over time were not significantly different for the 2 measures. Only the MFAB was significantly correlated with functional outcome as measured by the Specific Levels of Functioning Scale. Conclusions: The psychometric properties of the MFAB and UPSA-B were similar. The MATRICS scientific board chose to translate the MFAB into multiple languages for potential use in studies of novel medications seeking an indication for improving cognition in schizophrenia. © The Author 2013.


Mathis K.I.,VA Desert Pacific Mental Illness Research | Wynn J.K.,VA Desert Pacific Mental Illness Research | Wynn J.K.,University of California at Los Angeles | Jahshan C.,VA Desert Pacific Mental Illness Research | And 4 more authors.
International Journal of Psychophysiology | Year: 2012

When two visual targets are presented in a rapid serial visual presentation (RSVP) paradigm, the ability to identify the second target is reduced when it is presented 200-500. ms after the initial target. This phenomenon is referred to as the "attentional blink (AB)." Previous behavioral studies have reported aberrant AB in schizophrenia. The underlying cause, however, of the AB deficit in schizophrenia remains ambiguous. Individuals with schizophrenia consistently demonstrate impairments in early visual processing stages and later attentionally-mediated stages, yet the stage of processing that is contributing to patient-control differences on AB is unknown. The current study attempted to resolve this ambiguity by applying electrophysiological methodology to an RSVP paradigm with 70 clinically stable outpatients with schizophrenia and 63 healthy controls. The task was simplified to reduce task demands, and a suppression ratio was employed to control for possible differences between groups in the ability to identify a single stimulus within a visual stream. Early perceptual processing was assessed using the steady-state visual evoked potential (ssVEP), and attentional processing was assessed using the P300 event-related potential. Relative to the healthy controls, patients showed the expected behavioral AB deficits. These deficits coincided with reduced P300 amplitude: both performance and P300 reductions extended beyond the traditional AB window. Mean ssVEP amplitude did not differ between the groups, and the differences in P300 remained after controlling for ssVEP. These results suggest that the observed AB deficits were due to attentional, not perceptual, processing deficits. © 2012.


Davis M.C.,University of California at Los Angeles | Davis M.C.,VA Desert Pacific Mental Illness Research | Green M.F.,University of California at Los Angeles | Green M.F.,VA Desert Pacific Mental Illness Research | And 9 more authors.
Neuropsychopharmacology | Year: 2014

Impairments in social cognition are common in schizophrenia and predict poor functional outcome. The purpose of this proof-of-concept randomized, parallel group clinical trial was to assess whether intranasal oxytocin (OT), given before social cognitive training, enhances learning of social cognitive skills. Twenty seven male outpatients with schizophrenia participated in a 6-week (12 session) training on social cognitive skills. Training focused on three domains: facial affect recognition, social perception, and empathy. Subjects were randomly assigned (double blind) to receive either intranasal OTor placebo 30 min before each session. Participants did not receive OT between sessions or on the day of assessments. We evaluated scores on social-cognition measures, as well as clinical symptoms and neurocognition, at baseline, 1 week following the final training session, and 1 month later. Our prespecified primary outcome measure was a social-cognition composite score comprised of five individual measures. There were main effects of time (indicating improvement across the combined-treatment groups) on the social-cognition composite score at both 1 week and 1 month following completion of training. Subjects receiving OT demonstrated significantly greater improvements in empathic accuracy than those receiving placebo at both posttreatment and 1 month follow up. There were no OT-related effects for the other social cognitive tests, clinical symptoms, or neurocognition. This study provides initial support for the idea that OT enhances the effectiveness of training when administered shortly before social cognitive training sessions. The effects were most pronounced on empathic accuracy, a high-level social cognitive process that is not easily improved in current social cognitive remediation programs. © 2014 American College of Neuropsychopharmacology. All rights reserved.


Armstrong N.P.,San Francisco Veterans Affairs Medical Center | Cohen A.N.,VA Desert Pacific Mental Illness Research | Cohen A.N.,University of California at Los Angeles | Hellemann G.,University of California at Los Angeles | And 4 more authors.
Psychiatric Services | Year: 2014

Objective: This study explored the psychometric properties of the 30-item Mental Health Recovery Measure (MHRM) and a brief, ten-item version of the scale (MHRM-10) in a large, multisite sample of individuals with schizophrenia. Methods: The sample consisted of 795 veterans with schizophrenia or schizoaffective disorder diagnoses who were receiving mental health services in one of eight Veterans Health Administration medical centers across four regions of the United States. Exploratory factor analysis was used to examine the factor structure of the MHRM and to select the most appropriate ten items for the brief measure. Correlations of the MHRM and the MHRM-10 with measures of quality of life, satisfaction with mental health services, symptom severity, and functioning were computed to further establish construct validity. Cronbach' s alpha was used to assess the internal reliability of the MHRM and MHRM-10. Results: Factor analysis resulted in an interpretable single-factor solution. The MHRM-10 was established by selecting the ten items with the highest factor loading scores. MHRM and MHRM-10 total scores correlated strongly and positively with quality-of-life measures (overall, leisure, general health, and daily activities) and negatively with depressive mood. Negligible correlations existed between the MHRM instruments and measures of functioning and satisfaction with services. Both instruments demonstrated excellent internal consistency. Conclusions: This study provides initial support for use of theMHRM-10 as a brief, valid, and reliable assessment of perceived recovery among individuals with schizophrenia and one that may be easily used in routine care. © 2014, American Psychiatric Association. All rights reserved.


PubMed | VA Desert Pacific Mental Illness Research
Type: Journal Article | Journal: Community mental health journal | Year: 2011

In schizophrenia, treatments that improve outcomes have not been reliably disseminated. A major barrier to improving care has been a lack of routinely collected outcomes data that identify patients who are failing to improve or not receiving effective treatments. To support high quality care, the VA Mental Health QUERI used literature review, expert interviews, and a national panel process to increase consensus regarding outcomes monitoring instruments and strategies that support quality improvement. There was very good consensus in the domains of psychotic symptoms, side-effects, drugs and alcohol, depression, caregivers, vocational functioning, and community tenure. There are validated instruments and assessment strategies that are feasible for quality improvement in routine practice.

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