Michael F Green

Harvard University, Cambridge, Massachusetts, United States

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Publications (293)

  • Yvonne S. Yang · Stephen R. Marder · Michael F. Green
    [Show abstract] [Hide abstract] ABSTRACT: Currently-approved treatments for schizophrenia only minimally affect the cognitive features of the illness that are the most closely related to disability. Hence, there is now considerable effort to repurpose drugs for schizophrenia, and to seek agents that can improve cognition by targeting receptor systems other than the dopaminergic system. The results of these studies have been mixed thus far, however this continues to be a high-priority area of schizophrenia research and an important unmet need. This article is protected by copyright. All rights reserved.
    Article · Oct 2016 · Clinical Pharmacology &#38 Therapeutics
  • Charles M. Olbert · David L. Penn · Steven P. Reise · [...] · Michael F. Green
    [Show abstract] [Hide abstract] ABSTRACT: Attachment has recently been proposed as a key developmental construct in psychosis, in particular with respect to interpersonal functioning and social cognition. The current study examined the latent structure of the self-report Psychosis Attachment Measure (PAM) and its relationship to lower-level perceptual and higher-order inferential social cognitive processes. The PAM was administered to 138 psychiatrically stable outpatients with schizophrenia alongside a battery of symptom, social cognitive, and functional measures. PAM responses were analyzed using latent variable measurement models, which did not yield evidence of the coherent two-dimensional structure predicted by previous literature. A unidimensional subscale comprising 6 of the 16 original PAM items possessed the strongest psychometric properties. This subscale was generally uncorrelated with social cognitive measures and showed weak correlations with some symptoms measures and with community functioning. These results suggest that either the PAM may not measure attachment in psychosis or it may measure only attachment anxiety but demonstrate little construct validity in this population. These results tell a cautionary tale regarding making theoretical inferences on the basis of measures without coherent latent structure. Attachment measures with stronger psychometric properties will help clarify putative relationships between attachment and social cognitive processes in psychosis.
    Article · Sep 2016
  • Junghee Lee · Michael F. Green
    [Show abstract] [Hide abstract] ABSTRACT: Impaired social functioning is pervasive in schizophrenia. Unfortunately, existing treatments have limited efficacy, and possible psychological or neurobiological mechanisms underlying social dysfunction in this disorder remain obscure. Here, we evaluate whether social preference, one key aspect of social processing that has been largely overlooked in schizophrenia research, and N-methyl-d-aspartate receptor (NMDAR) dysfunction can provide insights into the mechanism underlying social dysfunction in schizophrenia. Based on evidence from developmental psychology, and behavioral and clinical neuroscience, we propose a heuristic model in which reduced NMDAR function may induce disrupted social preference that can subsequently lead to social cognitive impairment and social disability. We discuss its implications in terms of the pathophysiology of schizophrenia, other disorders with marked social disability, and potential treatments.
    Article · Jul 2016 · Trends in Neurosciences
  • Amanda McCleery · Junghee Lee · Alan P. Fiske · [...] · Michael F. Green
    [Show abstract] [Hide abstract] ABSTRACT: Background: Individuals with schizophrenia exhibit marked and disproportional impairment in social cognition, which is associated with their level of community functioning. However, it is unclear whether social cognitive impairment is stable over time, or if impairment worsens as a function of illness chronicity. Moreover, little is known about the longitudinal associations between social cognition and community functioning. Method: Forty-one outpatients with schizophrenia completed tests of emotion processing (Mayer-Salovey-Caruso Emotional Intelligence Test, MSCEIT) and social perception (Relationships Across Domains, RAD) at baseline and approximately five years later. Stability of performance was assessed using paired t-tests and correlations. Longitudinal associations between social cognition and community functioning (Role Functioning Scale, RFS) were assessed using cross-lagged panel correlation analysis. Results: Performance on the two social cognition tasks were stable over follow-up. There were no significant mean differences between assessment points [p's≥0.20, Cohen'sd's≤|0.20|], and baseline performance was highly correlated with performance at follow-up [ρ's≥0.70, ICC≥0.83, p's<0.001]. The contemporaneous association between social cognition and community functioning was moderately large at follow-up [ρ=0.49, p=0.002]. However, baseline social cognition did not show a significant longitudinal influence on follow-up community functioning [z=0.31, p=0.76]. Conclusions: These data support trait-like stability of selected areas of social cognition in schizophrenia. Cross-lagged correlations did not reveal a significant unidirectional influence of baseline social cognition on community functioning five years later. However, consistent with the larger literature, a moderately large cross-sectional association between social cognition and community functioning was observed. Based on stability and cross-sectional associations, these results suggest that social cognition might have short-term implications for functional outcome rather than long-term consequences.
    Article · Jul 2016 · Schizophrenia Research
  • Eric A. Reavis · Junghee Lee · Jonathan K. Wynn · [...] · Michael F. Green
    [Show abstract] [Hide abstract] ABSTRACT: Patients with schizophrenia show specific abnormalities in visual perception, and patients with bipolar disorder may have related perceptual deficits. During tasks that highlight perceptual dysfunction, patients with schizophrenia show abnormal activity in visual brain areas, including the lateral occipital complex (LOC) and early retinotopic cortex. It is unclear whether the anatomical structure of those visual areas is atypical in schizophrenia and bipolar disorder. In members of those two patient groups and healthy controls, we localized LOC and early retinotopic cortex individually for each participant using functional magnetic resonance imaging (MRI), then measured the thickness of those regions of interest using structural MRI scans. In both regions, patients with schizophrenia had the thinnest cortex, controls had the thickest cortex, and bipolar patients had intermediate cortical thickness. A control region, motor cortex, did not show this pattern of group differences. The thickness of each visual region of interest was significantly correlated with performance on a visual object masking task, but only in schizophrenia patients. These findings suggest an anatomical substrate for visual processing abnormalities that have been found with both neural and behavioral measures in schizophrenia and other severe mental illnesses.
    Article · May 2016 · Cerebral Cortex
  • L. Felice Reddy · Michael F. Green · Jonathan K. Wynn · [...] · William P. Horan
    [Show abstract] [Hide abstract] ABSTRACT: Motivational deficits are important determinants of impaired social functioning in schizophrenia, yet we know very little about their precise nature. One influential model of motivation distinguishes between approach and avoidance neurobiological systems that impact the tendency to approach rewarding and avoid threatening stimuli. The current study evaluated approach and avoidance motivational tendencies using both implicit and explicit measures. One-hundred and sixteen individuals with schizophrenia and 73 healthy controls completed the implicit Approach Avoidance Task (AAT) which provides a reaction time-based measure of approach and avoidance tendencies for happy and angry faces, and the Behavioral Inhibition/Behavioral Activation System Scale (BIS/BAS), a self-report measure of approach and avoidance tendencies. The patient sample was re-administered the AAT four weeks later to evaluate re-test reliability. At baseline, patients showed a significant tendency to approach (rather than avoid) angry faces on the AAT. This same pattern was replicated at the follow-up assessment. In contrast, on the BIS/BAS, patients reported significantly elevated BIS scores, reflecting increased avoidance of aversive, anxiety-inducing stimuli. Results suggest a discrepancy between patients' implicit behavioral tendency to approach angry faces and their self-reported avoidance of aversive stimuli.
    Article · May 2016 · Schizophrenia Research
  • Naomi T. Tabak · Michael F. Green
    Chapter · Apr 2016
  • Walter Dunn · Yuri Rassovsky · Jonathan K. Wynn · [...] · Michael F. Green
    [Show abstract] [Hide abstract] ABSTRACT: This study used bilateral transcranial direct current stimulation (tDCS) to target neural generators of auditory Mismatch Negativity (MMN) and oddball P300 in schizophrenia patients. tDCS was applied to the pre-frontal cortex in a parallel between-group design. There was a significant main effect of stimulation resulting in modulation of MMN amplitude. This effect was mainly driven by a non-significant, but large, effect-size decrease in MMN amplitude with anodal stimulation. This is the first study to demonstrate that tDCS is able to engage and modulate an EEG-based auditory processing measure in schizophrenia.
    Article · Apr 2016 · Schizophrenia Research
  • [Show abstract] [Hide abstract] ABSTRACT: Past studies describe numerous endophenotypes associated with schizophrenia (SZ), but many endophenotypes may overlap in information they provide, and few studies have investigated the utility of a multivariate index to improve discrimination between SZ and healthy community comparison subjects (CCS). We investigated 16 endophenotypes from the first phase of the Consortium on the Genetics of Schizophrenia, a large, multi-site family study, to determine whether a subset could distinguish SZ probands and CCS just as well as using all 16.Participants included 345 SZ probands and 517 CCS with a valid measure for at least one endophenotype. We used both logistic regression and random forest models to choose a subset of endophenotypes, adjusting for age, gender, smoking status, site, parent education, and the reading subtest of the Wide Range Achievement Test. As a sensitivity analysis, we re-fit models using multiple imputations to determine the effect of missing values.We identified four important endophenotypes: antisaccade, Continuous Performance Test-Identical Pairs 3-digit version, California Verbal Learning Test, and emotion identification. The logistic regression model that used just these four endophenotypes produced essentially the same results as the model that used all 16 (84% vs. 85% accuracy).While a subset of endophenotypes cannot replace clinical diagnosis nor encompass the complexity of the disease, it can aid in the design of future endophenotypic and genetic studies by reducing study cost and subject burden, simplifying sample enrichment, and improving the statistical power of locating those genetic regions associated with schizophrenia that may be the easiest to identify initially.
    Article · Apr 2016 · Schizophrenia Research
  • Amy M. Jimenez · Junghee Lee · Jonathan K. Wynn · [...] · Michael F. Green
    [Show abstract] [Hide abstract] ABSTRACT: Early visual perception and attention are impaired in schizophrenia, and these deficits can be observed on target detection tasks. These tasks activate distinct ventral and dorsal brain networks which support stimulus-driven and goal-directed attention, respectively. We used single and dual target rapid serial visual presentation (RSVP) tasks during fMRI with an ROI approach to examine regions within these networks associated with target detection and the attentional blink (AB) in 21 schizophrenia outpatients and 25 healthy controls. In both tasks, letters were targets and numbers were distractors. For the dual target task, the second target (T2) was presented at 3 different lags after the first target (T1) (lag1=100ms, lag3=300ms, lag7=700ms). For both single and dual target tasks, patients identified fewer targets than controls. For the dual target task, both groups showed the expected AB effect with poorer performance at lag 3 than at lags 1 or 7, and there was no group by lag interaction. During the single target task, patients showed abnormally increased deactivation of the temporo-parietal junction (TPJ), a key region of the ventral network. When attention demands were increased during the dual target task, patients showed overactivation of the posterior intraparietal cortex, a key dorsal network region, along with failure to deactivate TPJ. Results suggest inefficient and faulty suppression of salience-oriented processing regions, resulting in increased sensitivity to stimuli in general, and difficulty distinguishing targets from non-targets.
    Article · Mar 2016 · Frontiers in Psychology
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    Amy M. Jimenez · Junghee Lee · Jonathan K. Wynn · [...] · Michael F. Green
    File available · Dataset · Mar 2016
  • Michael F. Green
    [Show abstract] [Hide abstract] ABSTRACT: Schizophrenia is a severely disabling disease that affects millions of people worldwide. The notion of recovery from schizophrenia has recently become a topic of both research and clinical focus. With the advent of antipsychotic medications in the 1950s, many more patients achieved symptom remission than ever before. However, less than half of all patients have been able to achieve recovery. With so many drugs available to improve the symptoms of schizophrenia, why is the disorder still associated with such severe disability? In the last couple of decades, researchers and clinicians have begun to realize that a hindrance to widespread recovery is that available antipsychotic medications have been effective in treating the positive symptoms (hallucinations and delusions) of schizophrenia but not other features of illness such as cognitive impairment. Dysfunction in cognition and social cognition has a significant impact on patients' functional status, meaning that impaired cognition and social cognition should be treatment targets to improve the likelihood of recovery.
    Article · Feb 2016 · The Journal of Clinical Psychiatry
  • Lena Felice Reddy · James A Waltz · Michael F Green · [...] · William P Horan
    [Show abstract] [Hide abstract] ABSTRACT: Although individuals with schizophrenia show impaired feedback-driven learning on probabilistic reversal learning (PRL) tasks, the specific factors that contribute to these deficits remain unknown. Recent work has suggested several potential causes including neurocognitive impairments, clinical symptoms, and specific types of feedback-related errors. To examine this issue, we administered a PRL task to 126 stable schizophrenia outpatients and 72 matched controls, and patients were retested 4 weeks later. The task involved an initial probabilistic discrimination learning phase and subsequent reversal phases in which subjects had to adjust their responses to sudden shifts in the reinforcement contingencies. Patients showed poorer performance than controls for both the initial discrimination and reversal learning phases of the task, and performance overall showed good test-retest reliability among patients. A subgroup analysis of patients (n = 64) and controls (n = 49) with good initial discrimination learning revealed no between-group differences in reversal learning, indicating that the patients who were able to achieve all of the initial probabilistic discriminations were not impaired in reversal learning. Regarding potential contributors to impaired discrimination learning, several factors were associated with poor PRL, including higher levels of neurocognitive impairment, poor learning from both positive and negative feedback, and higher levels of indiscriminate response shifting. The results suggest that poor PRL performance in schizophrenia can be the product of multiple mechanisms.
    Article · Feb 2016 · Schizophrenia Bulletin
  • William P Horan · Jonathan K Wynn · Greg Hajcak · [...] · Michael F Green
    [Show abstract] [Hide abstract] ABSTRACT: Schizophrenia and bipolar disorder are associated with different clinical profiles of disturbances in motivation, yet few studies have compared the neurophysiological correlates of such disturbances. Outpatients with schizophrenia (n = 34), or bipolar disorder I (n = 33), and healthy controls (n = 31) completed a task in which the late positive potential (LPP), an index of motivated attention, was assessed along motivational gradients determined by apparent distance from potential rewards or punishments. Sequences of cues signaling possible monetary gains or losses appeared to loom progressively closer to the viewer; a reaction time (RT) task after the final cue determined the outcome. Controls showed the expected pattern with LPPs for appetitive and aversive cues that were initially elevated, smaller during intermediate positions, and escalated just prior to the RT task. The clinical groups showed different patterns in the final positions just prior to the RT task: the bipolar group's LPPs to both types of cues peaked relatively early during looming sequences and subsequently decreased, whereas the schizophrenia group showed relatively small LPP escalations, particularly for aversive cues. These distinct patterns suggest that the temporal unfolding of attentional resource allocation for motivationally significant events may qualitatively differ between these disorders. (PsycINFO Database Record
    Article · Feb 2016 · Journal of Abnormal Psychology
  • [Show abstract] [Hide abstract] ABSTRACT: The MATRICS Consensus Cognitive Battery (MCCB) fills a significant need for a standardized battery of cognitive tests to use in clinical trials for schizophrenia in adults aged 20-59. A need remains, however, to develop norms for younger individuals, who also show elevated risks for schizophrenia. Toward this end, we assessed performance in healthy adolescents. Baseline MCCB, reading and IQ data were obtained from healthy controls (ages 12-19) participating in two concurrent NIMH-funded studies: North American Prodromal Longitudinal Study phase 2 (NAPLS-2; n=126) and Boston Center for Intervention Development and Applied Research (CIDAR; n=13). All MCCB tests were administered except the Managing Emotions subtest from the Mayer-Salovey-Caruso Emotional Intelligence Test. Data were collected from 8 sites across North America. MCCB scores were presented in four 2-year age cohorts as T-scores for each test and cognitive domain, and analyzed for effects of age and sex. Due to IQ differences between age-grouped subsamples, IQ served as a covariate in analyses. Overall and sex-based raw scores for individual MCCB tests are presented for each age-based cohort. Adolescents generally showed improvement with age in most MCCB cognitive domains, with the clearest linear trends in Attention/Vigilance and Working Memory. These control data show that healthy adolescence is a dynamic period for cognitive development that is marked by substantial improvement in MCCB performance through the 12-19 age range. They also provide healthy comparison raw scores to facilitate clinical evaluations of adolescents, including those at risk for developing psychiatric disorders such as schizophrenia-related conditions.
    Article · Feb 2016 · Schizophrenia Research
  • William P. Horan · Amy M. Jimenez · Junghee Lee · [...] · Michael F. Green
    [Show abstract] [Hide abstract] ABSTRACT: Although it has been proposed that schizophrenia is characterized by impaired empathy, several recent studies found intact neural responses on tasks measuring the affective subdomain of empathy. This study further examined affective empathy in 21 schizophrenia outpatients and 21 healthy controls using a validated pain empathy paradigm with two components: (a) observing videos of people described as medical patients who were receiving a painful sound stimulation treatment; (b) listening to the painful sounds (to create Regions of Interest). The observing videos component incorporated experimental manipulations of perspective taking (instructions to imagine "Self" vs. "Other" experiencing pain) and cognitive appraisal (information about whether treatment was "Effective" vs. "Not Effective"). When considering activation across experimental conditions, both groups showed similar dorsal anterior cingulate cortex (dACC) and anterior insula (AI) activation while merely observing others in pain. However, there were group differences associated with perspective taking: controls showed relatively greater dACC and AI activation for the Self vs. Other contrast whereas patients showed relatively greater activation in these and additional regions for the Other vs. Self contrast. Although patients demonstrated grossly intact neural activity while observing others in pain, they showed more subtle abnormalities when required to toggle between imagining themselves versus others experiencing pain.
    Article · Jan 2016 · Social Cognitive and Affective Neuroscience
  • [Show abstract] [Hide abstract] ABSTRACT: The Consortium on the Genetics of Schizophrenia Family Study (COGS-1) has previously reported our efforts to characterize the genetic architecture of 12 primary endophenotypes for schizophrenia. We now report the characterization of 13 additional measures derived from the same endophenotype test paradigms in the COGS-1 families. Nine of the measures were found to discriminate between schizophrenia patients and controls, were significantly heritable (31 to 62%), and were sufficiently independent of previously assessed endophenotypes, demonstrating utility as additional endophenotypes. Genotyping via a custom array of 1536 SNPs from 94 candidate genes identified associations for CTNNA2, ERBB4, GRID1, GRID2, GRIK3, GRIK4, GRIN2B, NOS1AP, NRG1, and RELN across multiple endophenotypes. An experiment-wide p value of 0.003 suggested that the associations across all SNPs and endophenotypes collectively exceeded chance. Linkage analyses performed using a genome-wide SNP array further identified significant or suggestive linkage for six of the candidate endophenotypes, with several genes of interest located beneath the linkage peaks (e.g., CSMD1, DISC1, DLGAP2, GRIK2, GRIN3A, and SLC6A3). While the partial convergence of the association and linkage likely reflects differences in density of gene coverage provided by the distinct genotyping platforms, it is also likely an indication of the differential contribution of rare and common variants for some genes and methodological differences in detection ability. Still, many of the genes implicated by COGS through endophenotypes have been identified by independent studies of common, rare, and de novo variation in schizophrenia, all converging on a functional genetic network related to glutamatergic neurotransmission that warrants further investigation.
    Article · Nov 2015 · Schizophrenia Research
  • [Show abstract] [Hide abstract] ABSTRACT: Objective: The Consortium on the Genetics of Schizophrenia Family Study evaluated 12 primary and other supplementary neurocognitive and neurophysiological endophenotypes in schizophrenia probands and their families. Previous analyses of prepulse inhibition (PPI) and P50 gating measures in this sample revealed heritability estimates that were lower than expected based on earlier family studies. Here the authors investigated whether gating measures were more heritable in multiply affected families with a positive family history compared with families with only a single affected proband (singleton). Method: A total of 296 nuclear families consisting of a schizophrenia proband, at least one unaffected sibling, and both parents underwent a comprehensive endophenotype and clinical characterization. The Family Interview for Genetic Studies was administered to all participants and used to obtain convergent psychiatric symptom information for additional first-degree relatives. Among the families, 97 were multiply affected, and 96 were singletons. Results: Both PPI and P50 gating displayed substantially increased heritability in the 97 multiply affected families (47% and 36%, respectively) compared with estimates derived from the entire sample of 296 families (29% and 20%, respectively). However, no evidence for heritability was observed for either measure in the 96 singleton families. Schizophrenia probands derived from the multiply affected families also displayed a significantly increased severity of clinical symptoms compared with those from singleton families. Conclusions: PPI and P50 gating measures demonstrate substantially increased heritability in schizophrenia families with a higher genetic vulnerability for illness, providing further support for the commonality of genes underlying both schizophrenia and gating measures.
    Article · Oct 2015 · American Journal of Psychiatry
  • Michael F Green · William P Horan · Junghee Lee
    [Show abstract] [Hide abstract] ABSTRACT: Individuals with schizophrenia exhibit impaired social cognition, which manifests as difficulties in identifying emotions, feeing connected to others, inferring people's thoughts and reacting emotionally to others. These social cognitive impairments interfere with social connections and are strong determinants of the degree of impaired daily functioning in such individuals. Here, we review recent findings from the fields of social cognition and social neuroscience and identify the social processes that are impaired in schizophrenia. We also consider empathy as an example of a complex social cognitive function that integrates several social processes and is impaired in schizophrenia. This information may guide interventions to improve social cognition in patients with this disorder.
    Article · Sep 2015 · Nature Reviews Neuroscience
  • Naomi T Tabak · William P Horan · Michael F Green
    [Show abstract] [Hide abstract] ABSTRACT: Mindfulness-based interventions are gaining empirical support as alternative or adjunctive treatments for a variety of mental health conditions, including anxiety, depression, and substance use disorders. Emerging evidence now suggests that mindfulness-based treatments may also improve clinical features of schizophrenia, including negative symptoms. However, no research has examined the construct of mindfulness and its correlates in schizophrenia. In this study, we examined self-reported mindfulness in patients (n=35) and controls (n=25) using the Five-Facet Mindfulness Questionnaire. We examined correlations among mindfulness, negative symptoms, and psychological constructs associated with negative symptoms and adaptive functioning, including motivation, emotion regulation, and dysfunctional attitudes. As hypothesized, patients endorsed lower levels of mindfulness than controls. In patients, mindfulness was unrelated to negative symptoms, but it was associated with more adaptive emotion regulation (greater reappraisal) and beliefs (lower dysfunctional attitudes). Some facets of mindfulness were also associated with self-reported motivation (behavioral activation and inhibition). These patterns of correlations were similar in patients and controls. Findings from this initial study suggest that schizophrenia patients may benefit from mindfulness-based interventions because they (a) have lower self-reported mindfulness than controls and (b) demonstrate strong relationships between mindfulness and psychological constructs related to adaptive functioning. Copyright © 2015 Elsevier B.V. All rights reserved.
    Article · Jul 2015 · Schizophrenia Research

Publication Stats

17k Citations


  • 2011-2013
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2012
    • Douglas Mental Health University Institute
      Montréal, Quebec, Canada
  • 2008
    • Duke University
      Durham, North Carolina, United States
  • 2007
    • Los Angeles Neurosurgical Institute
      Los Ángeles, California, United States
  • 2006-2007
    • California State University, Northridge
      • Department of Psychology
      Los Angeles, CA, United States
    • University of California, San Diego
      • Department of Psychiatry
      San Diego, California, United States
  • 2005
    • University of Houston
      • Department of Psychology
      Houston, Texas, United States
  • 2002
    • Pacific Neuropsychiatric Institute
      Seattle, Washington, United States
    • University of California, Los Angeles
      • Department of Psychiatry and Biobehavioural Sciences
      Los Angeles, CA, United States
    • The Mental Illness Research, Education and Clinical Centers
      Washington, Washington, D.C., United States
  • 1999
    • University of Bergen
      • Department of Biological and Medical Psychology
      Bergen, Hordaland Fylke, Norway