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Computerized cognitive and social cognition training in schizophrenia for impulsive aggression

Khan, Anzalee; Lindenmayer, Jean-Pierre; Insel, Beverly; Seddo, Mary; Demirli, Ecem; DeFazio, Kayla; Sullivan, Mark; Hoptman, Matthew J; Ahmed, Anthony O
BACKGROUND:Schizophrenia is associated with an elevated risk for impulsive aggression for which there are few psychosocial treatment options. Neurocognitive and social cognitive deficits have been associated with aggression with social cognitive deficits seemingly a more proximal contributor. The current study examined the effects of combining cognitive and social cognition treatment on impulsive aggression among inpatients with chronic schizophrenia and schizoaffective disorder and a history of aggression compared to cognitive remediation treatment alone. METHODS:The two-center study randomized 130 participants to receive 36 sessions of either a combination of cognitive remediation and social cognition treatment or cognitive remediation plus a computer-based control. Participants had at least one aggressive incident within the past year or a Life History of Aggression (LHA) score of 5 or more. Participants completed measures of neurocognition, social cognition, symptom severity, and aggression at baseline and endpoint. RESULTS:Study participants were mostly male (84.5 %), had a mean age 34.9 years, and 11.5 years of education. Both Cognitive Remediation Training (CRT) plus Social Cognition Training (SCT) and CRT plus control groups were associated with significant reductions in aggression measures with no group differences except on a block of the Taylor Aggression Paradigm (TAP), a behavioral task of aggression which favored the CRT plus SCT group. Both groups showed significant improvements in neurocognition and social cognition measures with CRT plus SCT being associated with greater improvements. CONCLUSION/CONCLUSIONS:CRT proved to be an effective non-pharmacological treatment in reducing impulsive aggression in schizophrenia inpatient participants with a history of aggressive episodes. The addition of social cognitive training did not enhance this anti-aggression treatment effect but did augment the CRT effect on cognitive functions, on emotion recognition and on mentalizing capacity of our participants.
PMID: 36424289
ISSN: 1573-2509
CID: 5384412

Efficacy of Transcranial Direct Current Stimulation to Improve Insight in Patients With Schizophrenia: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Adam, Ondine; Blay, Martin; Brunoni, Andre R; Chang, Hsin-An; Gomes, July S; Javitt, Daniel C; Jung, Do-Un; Kantrowitz, Joshua T; Koops, Sanne; Lindenmayer, Jean-Pierre; Palm, Ulrich; Smith, Robert C; Sommer, Iris E; Valiengo, Leandro do Costa Lane; Weickert, Thomas W; Brunelin, Jérôme; Mondino, Marine
BACKGROUND AND HYPOTHESIS/OBJECTIVE:Impaired insight into the illness and its consequences is associated with poor outcomes in schizophrenia. While transcranial direct current stimulation (tDCS) may represent a potentially effective treatment strategy to relieve various symptoms of schizophrenia, its impact on insight remains unclear. To investigate whether tDCS would modulate insight in patients with schizophrenia, we undertook a meta-analysis based on results from previous RCTs that investigated the clinical efficacy of tDCS. We hypothesize that repeated sessions of tDCS will be associated with insight improvement among patients. STUDY DESIGN/METHODS:PubMed and ScienceDirect databases were systematically searched to identify RCTs that delivered at least 10 tDCS sessions in patients with schizophrenia. The primary outcome was the change in insight score, assessed by the Positive and Negative Syndrome Scale (PANSS) item G12 following active tDCS sessions as opposed to sham stimulation. Effect sizes were calculated for all studies and pooled using a random-effects model. Meta-regression and subgroup analyses were conducted. STUDY RESULTS/RESULTS:Thirteen studies (587 patients with schizophrenia) were included. A significant pooled effect size (g) of -0.46 (95% CI [-0.78; -0.14]) in favor of active tDCS was observed. Age and G12 score at baseline were identified as significant moderators, while change in total PANSS score was not significant. CONCLUSIONS:Ten sessions of active tDCS with either frontotemporoparietal or bifrontal montage may improve insight into the illness in patients with schizophrenia. The effect of this treatment could contribute to the beneficial outcomes observed in patients following stimulation.
PMID: 35820035
ISSN: 1745-1701
CID: 5269122

Association Between the Use of Psychotropic Medications and the Risk of COVID-19 Infection Among Long-term Inpatients With Serious Mental Illness in a New York State-wide Psychiatric Hospital System

Nemani, Katlyn; Williams, Sharifa Z; Olfson, Mark; Leckman-Westin, Emily; Finnerty, Molly; Kammer, Jammie; Smith, Thomas E; Silverman, Daniel J; Lindenmayer, Jean-Pierre; Capichioni, Gillian; Clelland, James; Goff, Donald C
Importance/UNASSIGNED:Individuals with serious mental illness are at increased risk of severe COVID-19 infection. Several psychotropic medications have been identified as potential therapeutic agents to prevent or treat COVID-19 but have not been systematically examined in this population. Objective/UNASSIGNED:To evaluate the associations between the use of psychotropic medications and the risk of COVID-19 infection among adults with serious mental illness receiving long-term inpatient psychiatric treatment. Design, Setting, and Participants/UNASSIGNED:This retrospective cohort study assessed adults with serious mental illness hospitalized in a statewide psychiatric hospital system in New York between March 8 and July 1, 2020. The final date of follow-up was December 1, 2020. The study included 1958 consecutive adult inpatients with serious mental illness (affective or nonaffective psychoses) who received testing for SARS-CoV-2 by reverse transcriptase-polymerase chain reaction or antinucleocapsid antibodies and were continuously hospitalized from March 8 until medical discharge or July 1, 2020. Exposures/UNASSIGNED:Psychotropic medications prescribed prior to COVID-19 testing. Main Outcomes and Measures/UNASSIGNED:COVID-19 infection was the primary outcome, defined by a positive SARS-CoV-2 reverse transcriptase-polymerase chain reaction or antibody test result. The secondary outcome was COVID-19-related death among patients with laboratory-confirmed infection. Results/UNASSIGNED:Of the 2087 adult inpatients with serious mental illness continuously hospitalized during the study period, 1958 (93.8%) underwent testing and were included in the study; 1442 (73.6%) were men, and the mean (SD) age was 51.4 (14.3) years. A total of 969 patients (49.5%) had laboratory-confirmed COVID-19 infection that occurred while they were hospitalized; of those, 38 (3.9%) died. The use of second-generation antipsychotic medications, as a class, was associated with decreased odds of infection (odds ratio [OR], 0.62; 95% CI, 0.45-0.86), whereas the use of mood stabilizers was associated with increased odds of infection (OR, 1.23; 95% CI, 1.03-1.47). In a multivariable model of individual medications, the use of paliperidone was associated with decreased odds of infection (OR, 0.59; 95% CI, 0.41-0.84), and the use of valproic acid was associated with increased odds of infection (OR, 1.39; 95% CI, 1.10-1.76). Clozapine use was associated with reduced odds of mortality in unadjusted analyses (unadjusted OR, 0.25; 95% CI, 0.10-0.62; fully adjusted OR, 0.43; 95% CI, 0.17-1.12). Conclusions and Relevance/UNASSIGNED:In this cohort study of adults hospitalized with serious mental illness, the use of second-generation antipsychotic medications was associated with decreased risk of COVID-19 infection, whereas the use of valproic acid was associated with increased risk. Further research is needed to assess the mechanisms that underlie these findings.
PMID: 35522282
ISSN: 2574-3805
CID: 5213932

SIBAT-A Computerized Assessment Tool for Suicide Ideation and Behavior: Development and Psychometric Properties

Alphs, Larry; Fu, Dong-Jing; Williamson, David; Jamieson, Carol; Greist, John; Harrington, Magdalena; Lindenmayer, Jean-Pierre; McCullumsmith, Cheryl; Sheehan, David V; Shelton, Richard C; Wicks, Paul; Canuso, Carla M
Objective/UNASSIGNED:Most assessments of suicidal ideation and behavior (SIB) are limited by reliance on a single assessor, typically a clinician or patient, with scant detail on patient-related drivers of SIB and inability to detect rapid change in SIB. Furthermore, many techniques do not include a semistructured interview, increasing rater variability. The Suicide Ideation and Behavior Assessment Tool (SIBAT) addresses these limitations. Design/UNASSIGNED:More than 30 experts in scale development, statistics, and clinical management of suicidal patients collaborated over a greater than four-year period to develop the SIBAT. Input for content and validity was received from patients, clinicians, and regulatory authorities in the United States (US) and Europe. Psychometric properties of the SIBAT were evaluated in validation studies. Results/UNASSIGNED:The SIBAT is organized into eight independent patient- or clinician-rated modules with branching logic and scoring algorithms, which necessitates computerization. Patient-reported information is first captured in Modules 1 to 5. Thereafter, an experienced clinician reviews the patient's report, conducts a semistructured interview (Module 6), and assesses the patient's suicide risk (Module 7) and optimal antisuicide management (Module 8). Input from cognitive interviews of diverse adult, adolescent, and clinician participants was incorporated into the final version of the SIBAT. Psychometric testing demonstrated good inter-rater reliability (intraclass coefficient range: 0.68-0.82), intra-rater reliability (weighted-kappa range: 0.64-0.76), and concurrent validity with other instruments for assessing SIB. Conclusion/UNASSIGNED:Patient- and clinician-based assessments and the psychometric studies summarized in this report support the validity and reliability of the SIBAT for capturing critical information related to assessment of SIB in adolescents and adults at risk for suicide.
PMID: 35958973
ISSN: 2158-8333
CID: 5287302

Valbenazine Treatment of Tardive Dyskinesia and of Positive Symptoms

Lindenmayer, Jean-Pierre; Burke, Eugene; Tsuboyama, Gabriel; Chahal, Yasmeen; Grewal, Harpreet Kaur
PMID: 34668876
ISSN: 1533-712x
CID: 5084612

Participant Engagement and Symptom Improvement: Aripiprazole Tablets with Sensor for the Treatment of Schizophrenia

Cochran, Jeffrey M; Fang, Hui; Le Gallo, Christophe; Peters-Strickland, Timothy; Lindenmayer, Jean-Pierre; Reuteman-Fowler, J Corey
Purpose/UNASSIGNED:, comprising an ingestible event-marker sensor embedded in aripiprazole tablets, wearable sensor patches, and a smartphone application) reduced the incidence of psychiatric hospitalizations relative to oral standard-of-care antipsychotics. This analysis explored the relationship between AS engagement by participants and changes in participant performance and symptom-severity measures assessed by clinical raters. Participants and Methods/UNASSIGNED:This post hoc analysis used prospectively collected clinical data from a phase 3b clinical trial (NCT03892889). Outpatients had schizophrenia, were aged 18-65 years, and had ≥ 1 psychiatric hospitalization in the previous 48 months. Participants were grouped by study completion status and a k-means clustering algorithm based on AS utilization, resulting in 3 groups: discontinued (discontinued AS before month 3 of the study); moderate engagement (completed 3 months, used AS intermittently); and high engagement (completed 3 months, used AS regularly). Baseline to end-of-study differences for the Clinical Global Impression Scale (Severity of Illness and Improvement of Illness scales), Personal and Social Performance Scale, and Positive and Negative Syndrome Scale were calculated. Results/UNASSIGNED:< 0.05) and demonstrated significantly more improvement in symptoms than participants with less engagement. Conclusion/UNASSIGNED:Participants who completed 3 months of the study and had higher AS engagement experienced significantly greater improvement in their end-of-study clinical assessments versus participants who did not complete 3 months. Improvement may be related to more-consistent medication intake and better engagement with a digital health system.
PMID: 35923658
ISSN: 1177-889x
CID: 5288172

Healthcare Provider Engagement with a Novel Dashboard for Tracking Medication Ingestion: Impact on Treatment Decisions and Clinical Assessments for Adults with Schizophrenia

Cochran, Jeffrey M; Fang, Hui; Sonnenberg, John G; Cohen, Elan A; Lindenmayer, Jean-Pierre; Reuteman-Fowler, J Corey
Purpose/UNASSIGNED:Schizophrenia is a severe, chronic condition accounting for disproportionate healthcare utilization. Antipsychotics can reduce relapse rates, but the characteristics of schizophrenia may hinder medication adherence. A phase 3b open-label clinical trial used aripiprazole tablets with sensor (AS; includes pills with ingestible event-marker, wearable sensor patches and smartphone application) in adults with schizophrenia. This post hoc analysis explored how healthcare providers' (HCPs) usage of a dashboard that provided medication ingestion information impacted treatment decisions and clinical assessments. Patients and Methods/UNASSIGNED:) effect sizes. Results/UNASSIGNED:To ensure sufficient opportunity for AS engagement, 113 participants who completed ≥3 months on study were analyzed. HCPs most often accessed dashboard data regarding medication ingestion and missed doses. HCPs recommended adherence counseling and participant education most often. Participants whose HCPs used the dashboard more and recommended adherence counseling and participant education (n=61) improved significantly more than participants with less dashboard-active HCPs (n=49) in CGI-I mean score (2.9 versus 3.4 [p=0.004]), total PANSS (mean change: -9.2 versus -3.1 [p=0.0002]), PANSS positive subscale (-3.2 versus -1.5 [p=0.003]), PANSS general subscale (-4.3 versus -1.2 [p=0.02]), and Marder factor for negative symptoms (-1.9 versus 0.0 [p=0.03]). Most HCPs found the dashboard easy to use (74%) and helpful for improving conversations with participants about their treatment plan and progress (78%). Conclusion/UNASSIGNED:This provider dashboard may facilitate discussions with patients about regular medication-taking, which can improve patient outcomes.
PMID: 35928793
ISSN: 1176-6328
CID: 5288302

Noninvasive direct current stimulation for schizophrenia: a review

Lindenmayer, Jean-Pierre; Fitapelli, Brianna
PURPOSE OF REVIEW/OBJECTIVE:To provide an update of recent studies describing the effects of transcranial direct current stimulation (tDCS) on patients with schizophrenia, with particular focus on auditory verbal hallucinations (AVH), cognitive deficits, and negative symptoms. RECENT FINDINGS/RESULTS:As a low-cost, easy-to-use neuromodulation technique, tDCS may have clinical implications for those suffering from treatment-persistent AVH, negative symptoms, and cognitive symptoms in schizophrenia. Over the past decade, tDCS has shown no effects for negative symptoms, except when used at a high frequency of sessions, and inconclusive results for AVH and cognitive symptoms. The treatment has little to no adverse effects. SUMMARY/CONCLUSIONS:The studies reviewed here support the need for further investigation and empirical data regarding the use of tDCS. The underlying mechanisms of tDCS as well as the most effective stimulation parameters must be better understood. Findings support the need for increased duration and frequency of tDCS sessions. One of the next steps is the investigation of effects of concomitant nonpharmacological treatments with tDCS.
PMID: 33534422
ISSN: 1473-6578
CID: 4776442

Association Between Cardiovascular Risk Factors and Cognitive Impairment in People With Schizophrenia: A Systematic Review and Meta-analysis

Hagi, Katsuhiko; Nosaka, Tadashi; Dickinson, Dwight; Lindenmayer, Jean Pierre; Lee, Jimmy; Friedman, Joseph; Boyer, Laurent; Han, Mei; Abdul-Rashid, Nur Amirah; Correll, Christoph U
Importance/UNASSIGNED:Schizophrenia is associated with cognitive dysfunction and cardiovascular risk factors, including metabolic syndrome (MetS) and its constituent criteria. Cognitive dysfunction and cardiovascular risk factors can worsen cognition in the general population and may contribute to cognitive impairment in schizophrenia. Objective/UNASSIGNED:To study the association between cognitive dysfunction and cardiovascular risk factors and cognitive impairment in individuals with schizophrenia. Data Sources/UNASSIGNED:A search was conducted of Embase, Scopus, MEDLINE, PubMed, and Cochrane databases from inception to February 25, 2020, using terms that included synonyms of schizophrenia AND metabolic adversities AND cognitive function. Conference proceedings, clinical trial registries, and reference lists of relevant publications were also searched. Study Selection/UNASSIGNED:Studies were included that (1) examined cognitive functioning in patients with schizophrenia or schizoaffective disorder; (2) investigated the association of cardiovascular disease risk factors, including MetS, diabetes, obesity, overweight, obesity or overweight, hypertension, dyslipidemia, and insulin resistance with outcomes; and (3) compared cognitive performance of patients with schizophrenia/schizoaffective disorder between those with vs without cardiovascular disease risk factors. Data Extraction and Synthesis/UNASSIGNED:Extraction of data was conducted by 2 to 3 independent reviewers per article. Data were meta-analyzed using a random-effects model. Main Outcomes and Measures/UNASSIGNED:The primary outcome was global cognition, defined as a test score using clinically validated measures of overall cognitive functioning. Results/UNASSIGNED:Twenty-seven studies involving 10 174 individuals with schizophrenia were included. Significantly greater global cognitive deficits were present in patients with schizophrenia who had MetS (13 studies; n = 2800; effect size [ES] = 0.31; 95% CI, 0.13-0.50; P = .001), diabetes (8 studies; n = 2976; ES = 0.32; 95% CI, 0.23-0.42; P < .001), or hypertension (5 studies; n = 1899; ES = 0.21; 95% CI, 0.11-0.31; P < .001); nonsignificantly greater deficits were present in patients with obesity (8 studies; n = 2779; P = .20), overweight (8 studies; n = 2825; P = .41), and insulin resistance (1 study; n = 193; P = .18). Worse performance in specific cognitive domains was associated with cognitive dysfunction and cardiovascular risk factors regarding 5 domains in patients with diabetes (ES range, 0.23 [95% CI, 0.12-0.33] to 0.40 [95% CI, 0.20-0.61]) and 4 domains with MetS (ES range, 0.15 [95% CI, 0.03-0.28] to 0.40 [95% CI, 0.20-0.61]) and hypertension (ES range, 0.15 [95% CI, 0.04-0.26] to 0.27 [95% CI, 0.15-0.39]). Conclusions and Relevance/UNASSIGNED:In this systematic review and meta-analysis, MetS, diabetes, and hypertension were significantly associated with global cognitive impairment in people with schizophrenia.
PMID: 33656533
ISSN: 2168-6238
CID: 4828702

Augmentation With Pimavanserin in Treatment Refractory Schizophrenia: Case Report

Lindenmayer, Jean-Pierre; Rizvi, Sukaina
PMID: 33857029
ISSN: 1533-712x
CID: 4846242