Biomedical subjects

Michael F Green

Publications and source records attributed to Michael F Green.

At least 19 recordsLinked to original sources

PubMed2006

Social cognition in schizophrenia: relationships with neurocognition and negative symptoms.

Despite the growing importance of social cognition in schizophrenia, fundamental issues concerning the nature of social cognition in schizophrenia remain unanswered. One issue concerns the strength of the relationships between social cognition and key features of the disorder such as neurocognitive deficits and negative symptoms. The current study employed structural equation modeling to examine three key questions regarding the nature of social cognition in schizophrenia: 1) Are social cognition and neurocognition in schizophrenia better modeled as one or two separate constructs? 2) Are social cognition and negative symptoms in schizophrenia better modeled as one or two separate constructs?, and 3) When social cognition, neurocognition, and negative symptoms are included in a single model, is social cognition more closely related to neurocognition or to negative symptoms? In this cross sectional study, one hundred outpatients with schizophrenia or schizoaffective disorder were administered measures of social cognition, neurocognition, and negative symptoms. A two-factor model that represented social cognition and neurocognition as separate constructs fit the data significantly better than a one-factor model, suggesting that social cognition and neurocognition are distinct, yet highly related, constructs. Likewise, a two-factor model that represented social cognition and negative symptoms as separate constructs fit the data significantly better than a one-factor model, suggesting that social cognition and negative symptoms are distinct constructs. A three-factor model revealed that the relationship between social cognition and neurocognition was stronger than the relationship between social cognition and negative symptoms. The current findings start to provide insights into the structure of social cognition, neurocognition, and negative symptoms in schizophrenia.

Adult↗

PubMed2006

The Consortium on the Genetics of Endophenotypes in Schizophrenia: model recruitment, assessment, and endophenotyping methods for a multisite collaboration.

BACKGROUND: The Consortium on the Genetics of Schizophrenia (COGS) is an ongoing, National Institute of Mental Health-funded, 7-site collaboration investigating the occurrence and genetic architecture of quantitative endophenotypes related to schizophrenia. The purpose of this article is to provide a description of the COGS structure and methods, including participant recruitment and assessment. METHODS: The hypothesis-driven recruitment strategy ascertains families that include a proband with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of schizophrenia, and at least one unaffected full sibling available for genotyping and endophenotyping, along with parents available for genotyping and (optional depending on age) endophenotyping. The family structure is selected to provide contrast in quantitative endophenotypic traits and thus to maximize the power of the planned genetic analyses. Probands are recruited from many sources including clinician referrals, local National Alliance for the Mentally Ill chapters, and advertising via the media. All participants undergo a standardized protocol that includes clinical characterization, a blood draw for genotyping, and endophenotype assessments (P50 suppression, prepulse inhibition, antisaccade performance, continuous performance tasks, letter-number span, verbal memory, and a computerized neurocognitive battery). Investigators participate in weekly teleconferences to coordinate and evaluate recruitment, clinical assessment, endophenotyping, and continuous quality control of data gathering and analyses. Data integrity is maintained through use of a highly quality-assured, centralized web-based database. RESULTS: As of February 2006, 355 families have been enrolled and 688 participants have been endophenotyped, including schizophrenia probands (n = 154, M:F = 110:44), first-degree biological relatives (n = 343, M:F = 151:192), and community comparison subjects (n = 191, M:F = 81:110). DISCUSSION: Successful multisite genetics collaborations must institute standardized methodological criteria for assessment and recruitment that are clearly defined, well communicated, and uniformly applied. In parallel, studies utilizing endophenotypes require strict adherence to criteria for cross-site data acquisition, equipment calibration and testing and software equivalence, and continuous quality assurance for many measures obtained across sites. This report describes methods and presents the structure of the COGS as a model of multisite endophenotype genetic studies. It also provides demographic information after the first 2 years of data collection on a sample for whom the behavioral data and genetics of endophenotype performance will be fully characterized in future articles. Some issues discussed in the reviews that follow reflect the challenges of evaluating endophenotypes in studies of the genetic architecture of endophenotypes in schizophrenia.

Cooperative Behavior↗

PubMed2006

Successful multi-site measurement of antisaccade performance deficits in schizophrenia.

The antisaccade task is a promising schizophrenia endophenotype; it is stable over time and reflects neurophysiological deficits present in both schizophrenia subjects and their first-degree relatives. Meaningful genetic research requires large sample sizes that are best ascertained using multi-site study designs. To establish the criterion validity of the antisaccade task in a multi-site design, the Consortium on the Genetics of Schizophrenia (COGS) examined whether seven sites could detect previously reported antisaccade deficits in schizophrenia subjects. Investigators presented 3 blocks of 20 antisaccade stimuli to 143 schizophrenia subjects and 195 comparison subjects. Frequent collaborator communication, standardized training, and ongoing quality assurance optimized testing uniformity. Data were discarded from only 1.2% of subjects due to poor quality, reflecting the high fidelity of data collection and scoring methods. All sites detected a significant difference in the proportion of correct antisaccades between schizophrenia and comparison subjects (p<.02 at all sites); group differences in gain and latency were less robust. Regression analyses to adjust for the effects of group, site, age, gender, smoking, and parental education on the proportion of correct antisaccades revealed a significant effect of group, site, and age but no effect of gender, smoking, or parental education, and no group-by-site interactions. Intraclass correlations between proportion of correct antisaccades across the blocks of stimuli ranged from 0.87 to 0.93, demonstrating good within-session reliability at sites. These results confirm previous findings of antisaccade deficits in schizophrenia subjects and support the use of the antisaccade task as a potential schizophrenia endophenotype in multi-site genetic studies.

Adolescent↗

PubMed2006

Assessment of community functioning in people with schizophrenia and other severe mental illnesses: a white paper based on an NIMH-sponsored workshop.

People with schizophrenia frequently have significant problems in community functioning. Progress in developing effective interventions to ameliorate these problems has been slowed by the absence of reliable and valid measures that are suitable for use in clinical trials. The National Institute of Mental Health convened a workgroup in September 2005 to examine this issue and make recommendations to the field that would foster research in this area. This article reports on issues raised at the meeting. Many instruments have been developed to assess community functioning, but overall insufficient attention has been paid to psychometric issues and many instruments are not suitable for use in clinical trials. Consumer self-report, informant report, ratings by clinicians and trained raters, and behavioral assessment all can provide useful and valid information in some circumstances and may be practical for use in clinical trials. However, insufficient attention has been paid to when and how different forms of assessment and sources of information are useful or how to understand inconsistencies. A major limiting factor in development of reliable and valid instruments is failure to develop a suitable model of functioning and its primary mediators and moderators. Several examples that can guide thinking are presented. Finally, the field is limited by the absence of an objective gold standard of community functioning. Hence, outcomes must be evaluated in part by "clinical significance." This criterion is problematic because different observers and constituencies often have different opinions about what types of change are clinically important and how much change is significant.

Activities of Daily Living↗

PubMed2006

Exploring the short term visual store in schizophrenia using the attentional blink.

Schizophrenia patients exhibit numerous deficits on visual processing tasks, ranging from very early stages of visual processing (e.g., backward masking) to the later working memory stages (e.g., delayed match-to-sample, N-back). However, little is known about deficits in an intermediate stage of visual information processing, namely short term visual memory (STVM). The attentional blink (AB) paradigm is considered to be a valid way to assess the STVM, and recent studies have reported AB deficits in schizophrenia. However, it is not clear whether the reported AB deficit in schizophrenia patients is due to their increased susceptibility to backward masking or increased vulnerability in the STVM. In this study we first found poorer performance in the AB task in 37 schizophrenia patients compared to 26 normal controls. To examine the effects of increasing and decreasing mask strength on AB performance in patients and controls, we next systematically varied the masking effect by varying the length of the distracters immediately following the targets. The manipulation had relatively little effect on the patient--control differences and patients continued to show an enhanced AB effect across conditions. The findings suggest that the enhanced AB effect in schizophrenia reflects an abnormality in their short term visual memory, as opposed to their enhanced susceptibility to visual masking.

Adult↗

PubMed2006

An analysis of categorical perception of facial emotion in schizophrenia.

BACKGROUND: Emotion perception deficits have been extensively documented in schizophrenia and are associated with poor social functioning. Yet fundamental questions about the nature and scope of these impairments remain unanswered from commonly used experimental tasks. An alternative categorical perception paradigm that focuses on distinguishing boundaries between emotions was used to evaluate whether schizophrenia patients demonstrate atypical patterns of categorical perception and a negativity bias in the identification of ambiguous facial expressions. METHOD: 47 schizophrenia outpatients and 31 nonpsychiatric controls completed a forced-choice emotion identification task. Stimuli consisted of a series of digitized facial images that were morphed in 10% signal intensity increments along continua between pairs of emotions (happy-sad; fearful-happy; angry-fearful; angry-sad) and presented in a random order. For each emotion continuum, measures of the response slope and the location of the boundary shift point between emotions were calculated for each group. RESULTS: The schizophrenia group demonstrated significantly shallower response curves than controls across all emotion continua. Despite these generally less precise demarcations between emotions, patients did not significantly differ from controls in the location of the shift point between emotions on any of the continua. CONCLUSIONS: Schizophrenia patients demonstrated impaired categorical perception of facial expressions with generally less sharp categorizations of ambiguous stimuli to one emotion category or another. However, patients did not demonstrate a negativity bias in their processing of ambiguous facial expressions. The emotional continuum paradigm can help to clarify the nature and boundaries of affect perception deficits in schizophrenia.

Adolescent↗

PubMed2006

The neurocognitive effects of aripiprazole: an open-label comparison with olanzapine.

RATIONALE: Cognitive deficits are a core feature of schizophrenia. As a target of intervention, improvements in cognition may lead to improvements in functional outcome. OBJECTIVES: The present paper is the first report, to our knowledge, on the neurocognitive effects of aripiprazole. Unlike other second-generation antipsychotics, aripiprazole is a D(2) and D(3) receptor partial agonist. It is unknown what effects this unusual pharmacological profile may yield on neurocognition. MATERIALS AND METHODS: The present open-label study included data on 169 patients with schizophrenia or schizoaffective disorder who were randomly treated with aripiprazole or olanzapine. Subjects received a neurocognitive battery at baseline, week 8, and 26. RESULTS: The aripiprazole group had a significantly greater dropout rate than the olanzapine group. Neurocognitive data were reduced through a principal components analysis that yielded a three-factor solution. The factors were general cognitive functioning, executive functioning, and verbal learning. For general cognitive functioning, both groups improved from baseline and the effects were relatively stable over the 26-week protocol. There were no differential treatment effects. For executive functioning, neither group improved significantly from baseline. For verbal learning, the aripiprazole group improved significantly from baseline to the 8th and 26th week of assessment, and there was a between-group effect favoring aripiprazole over olanzapine that was largely attributable to the differences in performance within the 8th week. Separate analyses were conducted for a measure of sustained attention (Continuous Performance Test-Identical Pairs). There were no differential treatment effects on this measure. CONCLUSIONS: The findings from this open-label study suggest that the neurocognitive effects of aripiprazole are at least as good as those of olanzapine.

Adult↗

PubMed2006

The dimensions of clinical and cognitive change in schizophrenia: evidence for independence of improvements.

BACKGROUND: As cognitive impairments are related to deficits in everyday functioning in schizophrenia, treatment of these impairments may have the potential to reduce these functional deficits. To determine if treatments truly reduce cognitive impairment, it is important to discriminate direct cognitive effects of treatment from generalized treatment benefits on the multiple clinical dimensions of schizophrenia. Thus, this study used a database from an existing clinical trial and examined the relationships between changes in clinical symptoms and cognitive deficits with several different strategies. MATERIALS AND METHODS: Two hundred and seventy stable but symptomatic outpatients with schizophrenia entered a study where they were switched from previous treatment to open-label ziprasidone. The present data are from the 6-month endpoint (n=184). Patients were examined at baseline and the 6-month endpoint with ratings of clinical symptoms based on the Positive and Negative Syndrome Scale (PANSS) and a neuropsychological (NP) assessment battery including aspects of cognitive functioning known to be related to functional outcome in schizophrenia. RESULTS: Changes on the individual PANSS items and NP test scores were examined with two separate principal components analyses, revealing four dimensions of clinical change (psychosis, negative symptoms, affective symptoms, and agitation) and two dimensions of NP improvement. Pearson correlations between changes in the (1) factors derived from the analyses, (2) individual NP items based the four clinical dimensions of change, and (3) the 30 PANSS items and the two NP dimensions of change suggested minimal relationships (largest r=0.15). IMPLICATIONS: This sample was selected because previous findings suggested that clinical and NP symptoms of schizophrenia significantly improved from baseline after a switch to ziprasidone treatment. While four dimensions of change in clinical symptoms and two dimensions of cognitive improvements were identified, clinical changes, regardless of how they were defined, were not related to NP improvements.

Adolescent↗

PubMed2006

Dissociable mechanisms for memory impairment in bipolar disorder and schizophrenia.

BACKGROUND: Although memory deficits are consistently reported in schizophrenia and bipolar disorder, the mechanisms underlying these impairments are poorly understood. Clarifying the nature and degree of overlap in memory deficits between the two illnesses could help to distinguish brain systems disrupted in these illnesses, and indicate cognitive remediation strategies to improve patient outcomes. METHOD: We examined performance on a non-verbal memory task in clinically stable out-patients with bipolar disorder (n=40), schizophrenia (n=40), and healthy comparison subjects (n=40). This task includes conditions in which distinct mnemonic strategies -- namely, using context to organize familiar stimuli or using holistic representation of novel stimuli -- facilitate performance. RESULT: When compared to a reference condition, bipolar patients had deficits consistent with organizational dysfunction and poor detection of novel information. Although patients with schizophrenia performed worse than the other groups, they were only differentially impaired when organizational demands were significant. Task performance was not correlated with severity of clinical symptomatology. CONCLUSIONS: This pattern of distinct memory impairments implies disturbances in partially overlapping neural systems in bipolar disorder and schizophrenia. Evidence of impairment in detection of novel stimuli that is unique to bipolar disorder suggests that, while the absolute level of cognitive dysfunction is less severe in bipolar disorder as compared to schizophrenia, subtle disruptions in memory are present. These findings can be used to plan targeted cognitive remediation programs by helping patients to capitalize on intact functions and to learn new strategies that they do not employ without training.

Adult↗

PubMed2006

Neurocognitive and social cognitive correlates of formal thought disorder in schizophrenia patients.

The neurocognitive and social cognitive correlates of two types of formal thought disorder (i.e., bizarre-idiosyncratic and concrete thinking) were examined in 47 stable outpatients with schizophrenia. Both types of thinking disturbance were related to impairments in verbal learning, intrusions in verbal memory, immediate auditory memory, sustained attention, and social schema knowledge. Distractibility during an immediate memory task was associated with more frequent bizarre verbalizations but not concreteness. Impaired verbal learning rate and intrusions in verbal memory independently contributed to the prediction of bizarre responses, whereas intrusions in verbal memory and impaired immediate memory independently contributed to concrete thinking. This pattern of findings is consistent with the view that neurocognitive and, possibly, social cognitive deficits underlie these two aspects of formal thinking disturbance in schizophrenia.

Adult↗

PubMed2006

Baseline neurocognitive deficits in the CATIE schizophrenia trial.

Neurocognition is moderately to severely impaired in patients with schizophrenia. However, the factor structure of the various neurocognitive deficits, the relationship with symptoms and other variables, and the minimum amount of testing required to determine an adequate composite score has not been determined in typical patients with schizophrenia. An 'all-comer' approach to cognition is needed, as provided by the baseline assessment of an unprecedented number of patients in the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) schizophrenia trial. From academic sites and treatment providers representative of the community, 1493 patients with chronic schizophrenia were entered into the study, including those with medical comorbidity and substance abuse. Eleven neurocognitive tests were administered, resulting in 24 individual scores reduced to nine neurocognitive outcome measures, five domain scores and a composite score. Despite minimal screening procedures, 91.2% of patients provided meaningful neurocognitive data. Exploratory principal components analysis yielded one factor accounting for 45% of the test variance. Confirmatory factor analysis showed that a single-factor model comprised of five domain scores was the best fit. The correlations among the factors were medium to high, and scores on individual factors were very highly correlated with the single composite score. Neurocognitive deficits were modestly correlated with negative symptom severity (r=0.13-0.27), but correlations with positive symptom severity were near zero (r<0.08). Even in an 'all-comer' clinical trial, neurocognitive deficits can be assessed in the overwhelming majority of patients, and the severity of impairment is similar to meta-analytic estimates. Multiple analyses suggested that a broad cognitive deficit characterizes this sample. These deficits are modestly related to negative symptoms and essentially independent of positive symptom severity.

Adult↗

PubMed2006

Neurocognitive performance and functional disability in the psychosis prodrome.

OBJECTIVE: This study evaluates the pattern of neuropsychological deficits and their association with clinical symptomatology and social functioning in individuals identified as ultra-high-risk (UHR) for psychosis. METHODS: A sample of 45 UHR individuals was identified using the Structured Interview for Prodromal Syndromes (SIPS) from consecutive referrals to the Staglin Music Festival Center for the Assessment and Prevention of Prodromal States (CAPPS) at UCLA. Participants were administered a neurocognitive test battery, as well as measures of global (Strauss-Carpenter Outcome Scale) and social functioning (UCLA Social Attainment Survey). RESULTS: Participants showed significant deficits in speed of processing, verbal learning and memory, and motor speed. Poorer verbal learning and memory performance was significantly associated with poorer social functioning, and there was a trend for poorer performance on reasoning and problem solving to be associated with poorer global functioning. Verbal memory independently predicted social functioning over and above severity of negative symptoms. Cognitive deficits were not associated with severity of clinical symptomatology. CONCLUSIONS: Despite the absence of fully psychotic symptoms, UHR individuals experience significant cognitive deficits, particularly on tasks requiring speeded information-processing and efficient recall from memory, and these deficits appear to be associated with functional disability in a manner parallel to that observed in patients with established psychotic illness.

Adolescent↗

PubMed2006

Quantitative EEG and low resolution electromagnetic tomography (LORETA) imaging of patients with persistent auditory hallucinations.

Electrophysiological studies have demonstrated gamma and beta frequency oscillations in response to auditory stimuli. The purpose of this study was to test whether auditory hallucinations (AH) in schizophrenia patients reflect abnormalities in gamma and beta frequency oscillations and to investigate source generators of these abnormalities. This theory was tested using quantitative electroencephalography (qEEG) and low-resolution electromagnetic tomography (LORETA) source imaging. Twenty-five schizophrenia patients with treatment refractory AH, lasting for at least 2 years, and 23 schizophrenia patients with non-AH (N-AH) in the past 2 years were recruited for the study. Spectral analysis of the qEEG and source imaging of frequency bands of artifact-free 30 s epochs were examined during rest. AH patients showed significantly increased beta 1 and beta 2 frequency amplitude compared with N-AH patients. Gamma and beta (2 and 3) frequencies were significantly correlated in AH but not in N-AH patients. Source imaging revealed significantly increased beta (1 and 2) activity in the left inferior parietal lobule and the left medial frontal gyrus in AH versus N-AH patients. These results imply that AH is reflecting increased beta frequency oscillations with neural generators localized in speech-related areas.

Adult↗

PubMed2006

Does anhedonia in schizophrenia reflect faulty memory for subjectively experienced emotions?

The authors evaluated whether self-reported trait anhedonia in schizophrenia reflects faulty memory, such that patients are capable of experiencing pleasure while engaged in enjoyable activities but underestimate their pleasure in recalling these experiences. Thirty schizophrenia patients and 31 nonpatient control participants rated their emotional responses to pleasant and neutral foods and film clips and completed a surprise recall task for their emotions after a 4-hr delay. Despite reporting elevated trait anhedonia, patients did not significantly differ from control participants in immediate pleasant emotional responses to the stimuli or in delayed recall for these experiences. In-the-moment pleasure and short-term retention for emotional experiences thus appear to be relatively intact in schizophrenia. Alternative explanations for the hedonic deficit in this disorder are discussed.

Adult↗

PubMed2006

Social perception as a mediator of the influence of early visual processing on functional status in schizophrenia.

OBJECTIVE: The potential of social cognition as a mediator of relations between neurocognition and functional status in schizophrenia has been suggested by correlational studies that link neurocognition to social cognition or link social cognition to functional status. The authors used structural equation modeling to test more directly whether one aspect of social cognition (social perception) mediates relations between basic visual perception and functional status in patients with schizophrenia. METHOD: Seventy-five outpatients with schizophrenia were administered measures of early visual processing (computerized visual masking procedures), social perception (Half Profile of Nonverbal Sensitivity), and functional status (Role Functioning Scale). RESULTS: Structural equation modeling supported social perception as a mediator of relations between early visual processing and functional status in schizophrenia. The mediation model indicated that early visual processing is linked to functional status through social perception, thereby supporting a significant indirect relationship. The direct relationship between early visual processing and functional status was significant in a model that did not include social perception but was not significant in the mediation model that included social perception. CONCLUSIONS: Social cognition appears to be a key determinant of functional status in schizophrenia. Using a very basic measure of visual perception, the present study found that social perception mediates the influence of early visual processing on functional status in schizophrenia.

Ambulatory Care↗

PubMed2006

Cognitive impairment and functional outcome in schizophrenia and bipolar disorder.

A considerable amount of evidence supports the relationship between cognitive impairment and functional outcomes in schizophrenia. Cognitive impairment is considered a core feature of schizophrenia that includes problems in speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. These deficits can also serve as an endophenotype for the illness in studies of genetics. Cognition is considered a reasonable treatment target in individuals with schizophrenia, partly because cognitive deficits contribute to poor functional outcomes. Similarly, evidence is beginning to emerge that cognitive impairment may also be a core feature of bipolar disorder. In addition, cognitive deficits adversely affect functional outcomes in bipolar disorder. This evidence suggests that cognition can be considered a reasonable target for intervention in both schizophrenia and bipolar disorder.

Adult↗

PubMed2006

Cognitive impairment and functional outcome in schizophrenia and bipolar disorder.

Cognitive impairment in schizophrenia and that in bipolar disorder share some similarities. However, more literature exists on cognitive impairment in schizophrenia than in bipolar disorder. The NIMH Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Initiative has identified several cognitive domains that are dysfunctional in schizophrenia and should be considered in the context of clinical trials. Cognitive impairments in these domains are also seen in bipolar disorder, but they tend to be milder. These impairments seem to be a core feature of schizophrenia and exist outside of mood episodes in bipolar disorder. Impairments are present in unaffected relatives of patients with schizophrenia or bipolar disorder, can serve as an endophenotype for both illnesses, and are linked to community functioning.

Bipolar Disorder↗

PubMed2005

Visual processing in schizophrenia: Structural equation modeling of visual masking performance.

Schizophrenic patients consistently demonstrate performance deficits on visual masking procedures. In visual masking, the subject's ability to process a target stimulus is reduced by another stimulus (mask) presented either before (forward masking) or after (backward masking) the target. Masking procedures employed in schizophrenia research have used several experimental paradigms. Most early studies have used high-energy masks (i.e., the mask is stronger than the target) and spatially overlapping target and mask. More recently, studies have begun to employ relatively weak (i.e., low-energy) masks, as well as masks that surround, but do not spatially overlap, the target. Data for forward and backward masking components of four masking conditions (target location and identification with a high-energy mask, target identification with a low-energy mask, and target identification with equal energy paracontrast/metacontrast) were collected from 75 patients with schizophrenia. Based on theoretical distinctions among masking procedures, we compared four models of visual masking using structural equation modeling. Although high zero-order correlations were found among the masking parameters, a four-factor model, in which factors were separated on the type of response (target location and identification), the shape of the function (monotonic and non-monotonic), and the overlap of the stimuli (overlapping and non-overlapping), provided the best fit for the data. These findings suggest that the four masking procedures used in this study may tap unique aspects of visual processing and are not redundant. The results also support theories of the different mechanisms underlying performance on these measures.

Adult↗