Biomedical subjects

Michael F Green

Publications and source records attributed to Michael F Green.

At least 55 records · Page 3Linked to original sources

PubMed2004

Paracontrast and metacontrast in schizophrenia: clarifying the mechanism for visual masking deficits.

Schizophrenic patients consistently demonstrate performance deficits on visual masking procedures. Visual masking can occur through two distinctly different mechanisms: interruption and integration. One highly effective way to limit the masking mechanism to interruption is to use a mask that surrounds, but does not spatially overlap, the target. These procedures are called paracontrast and metacontrast (for forward and backward masking, respectively). Despite their clear advantages for interpretation, paracontrast and metacontrast have not been used previously in schizophrenia. In the present study, we examined the reliability of the paracontrast and metacontrast procedures by administering these tasks to 103 schizophrenic patients and 49 normal control subjects. In addition, we compared the results to those from a low-energy masking condition, which is an alternative way to limit masking to interruption. Patients showed deficits on both the paracontrast and metacontrast procedures. The deficits in paracontrast and metacontrast were comparable to those seen previously with low-energy masking. These results suggest that the paracontrast/metacontrast procedure and the procedure using a low-energy mask are roughly equally sensitive to deficits in early visual processing among schizophrenic patients. These results bolster previous conclusions that schizophrenic patients show deficits on visual masking tasks even when masking on those tasks occurs entirely through the interruption mechanism.

Adolescent↗

PubMed2004

Neurocognitive function in clinically stable men with bipolar I disorder or schizophrenia and normal control subjects.

BACKGROUND: Patients with bipolar disorder and schizophrenia have been shown to have neurocognitive deficits when compared with control subjects. The degree and pattern of impairment between psychiatric groups have rarely been compared, especially when subjects are psychiatrically stable. METHODS: Using a standard neurocognitive battery, we compared euthymic outpatients with bipolar disorder (n = 40), stable patients with schizophrenia (n = 20), and subjects with no psychiatric disorder (n = 22). The neurocognitive domains assessed included executive functioning, verbal memory, visual memory, procedural learning, visuoconstructive ability, and language functions. Effect sizes were calculated for each cognitive domain across groups. RESULTS: Stable schizophrenic subjects demonstrated a generalized cognitive impairment across most domains compared with control subjects, with average effect sizes of .9. Euthymic bipolar subjects were significantly impaired compared with control subjects only in executive functioning (Wisconsin Card Sorting Task) and verbal memory (California Verbal Learning Test) domains (effect sizes in the .8-.9 range). Performance on the executive function measures was bimodal among bipolar subjects, suggesting two subgroups: one with relatively normal and one with impaired executive functioning. No significant differences between the bipolar patient group and control subjects were observed in visuoconstructive ability, procedural learning, or language function. CONCLUSIONS: Both euthymic bipolar subjects and relatively stable schizophrenic subjects differed from control subjects in neurocognitive function. Among schizophrenic subjects, a generalized cognitive impairment was observed, and the degree of impairment was greater in the schizophrenic compared with the bipolar subjects. Subjects with bipolar disorder were impaired in two specific domains (verbal memory and executive function). Furthermore, within the bipolar group there was a subset with relatively normal executive functioning and a subset with significant impairment. Possible reasons for the persistence of these neurocognitive deficits in some subjects with bipolar disorder during periods of euthymia are reviewed.

Adult↗

PubMed2004

Approaching a consensus cognitive battery for clinical trials in schizophrenia: the NIMH-MATRICS conference to select cognitive domains and test criteria.

To stimulate the development of new drugs for the cognitive deficits of schizophrenia, the National Institute of Mental Health (NIMH) established the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative. This article presents an overview of decisions from the first MATRICS consensus conference. The goals of the meeting were to 1) identify the cognitive domains that should be represented in a consensus cognitive battery and 2) prioritize key criteria for selection of tests for the battery. Seven cognitive domains were selected based on a review of the literature and input from experts: working memory, attention/vigilance, verbal learning and memory, visual learning and memory, reasoning and problem solving, speed of processing, and social cognition. Based on discussions at this meeting, five criteria were considered essential for test selection: good test-retest reliability, high utility as a repeated measure, relationship to functional outcome, potential response to pharmacologic agents, and practicality/tolerability. The results from this meeting constitute the initial steps for reaching a consensus cognitive battery for clinical trials in schizophrenia.

Clinical Trials as Topic↗

PubMed2004

Self-efficacy and neurocognition may be related to coping responses in recent-onset schizophrenia.

Although stressful life events can trigger psychotic and depressive symptom exacerbation in schizophrenia, many patients who experience stressful events do not subsequently relapse. Models of vulnerability, stress, and protective factors in schizophrenia suggest that effective coping responses may serve as protective factors. Coping behavior, in turn, may be influenced by a schizophrenia patient's level of self-efficacy and neurocognitive functioning. Using the Coping Responses Inventory, we examined how 29 recent-onset schizophrenia outpatients and 24 demographically matched normal comparison subjects responded to a negative interpersonal life event. Approach oriented coping responses, such as "Think of different ways to deal with the problem" and "Make a plan of action and follow it," were used significantly more often by normal subjects (M=2.27) than by schizophrenia patients (M=1.89; p < 0.02). Among schizophrenia patients, greater use of approach, problem-focused coping strategies was associated with high self-efficacy (r=0.55, p < 0.01) and better performance on a measure of sustained attention emphasizing perceptual processing (r=0.42, p < 0.05). Multiple regression indicated that self-efficacy and sustained attention accounted for 56% of the variance in the use of problem-focused coping, strategies by schizophrenia patients.

Adaptation, Psychological↗

PubMed2004

The timing of negative symptom exacerbations in relationship to positive symptom exacerbations in the early course of schizophrenia.

Although positive and negative symptoms appear to represent independent symptom dimensions of psychopathology when evaluated cross-sectionally among individuals with schizophrenia, it is not known if exacerbations of symptoms on these two dimensions are independent. This prospective longitudinal study examined the temporal relationship between the positive and negative symptom exacerbations among 48 recent-onset schizophrenia or schizoaffective patients who received symptom ratings every 2 weeks on the Brief Psychiatric Rating Scale. Patients were followed for a period of at least 1 year and a mean of 3 years. To examine the temporal relationship between positive and negative symptoms, six time periods were defined in relation to psychotic exacerbation or relapse (e.g., prodromal, concurrent, post-psychotic) and used to compare the timing of positive and negative symptom exacerbations. A substantial proportion of patients had exacerbations of positive symptoms (77%) and negative (42%) symptoms. Negative symptom exacerbations occurred simultaneously with positive symptom exacerbations to a significantly greater extent than expected by chance, and occurred less frequently than expected by chance during the time period most temporally removed from positive symptom exacerbations. Results suggest that the timing of some negative symptom exacerbations is linked to that of positive symptom exacerbations during the early course of schizophrenia.

Adult↗

PubMed2004

Antipsychotic and anticholinergic effects on two types of spatial memory in schizophrenia.

Spatial memory is of interest in schizophrenia because of widespread impairments in adaptive functioning, including independent living skills. Short-term spatial memory is impaired in this disease, whereas spatial reference memory, a longer-term spatial memory, has not been evaluated. Animal studies have demonstrated that anticholinergics impair short-term spatial memory but not spatial reference memory. The effects of haloperidol and risperidone on these two types of spatial memory were evaluated in a double-blind randomized comparison in inpatients with schizophrenia. It was predicted that risperidone would have a greater beneficial effect on spatial working memory than haloperidol. Computerized measures of spatial working memory and spatial reference memory were developed based on animal assessment of these functions. Subjects with schizophrenia were assessed during a medication-free period and again following 4 weeks of fixed-dose treatment. Risperidone, compared to haloperidol, improved spatial working memory performance, an effect that became nonsignificant when benztropine co-treatment was controlled. There were no treatment effects on spatial reference memory performance. Consistent with animal studies, benztropine impaired spatial working memory but not spatial reference memory. The relative benefits of risperidone on spatial working memory performance were largely explained by differential benztropine treatment for the haloperidol-treated subjects.

Adult↗

PubMed2004

Prepulse facilitation and prepulse inhibition in schizophrenia patients and their unaffected siblings.

BACKGROUND: Deficits in schizophrenia patients and their first-degree relatives have been reported in prepulse inhibition (PPI), a phenomenon that measures an early stage of information processing (sensorimotor gating). It is less clear whether these information processing deficits extend to prepulse facilitation (PPF), which measures a later stage of generalized alerting or orienting. METHODS: This study examined three separate issues: first, whether schizophrenia patients have deficits in PPI and PPF; second, whether the siblings of patients show deficits in these processes; and third, whether prepulse duration influences the degree of the deficits. These issues were examined in 76 schizophrenia patients, 36 of their siblings, and 41 normal control subjects. RESULTS: Patients and siblings did not differ from control subjects in PPI, perhaps due to the use of different procedural parameters compared with other laboratories that have consistently found PPI deficits in schizophrenia patients. Patients and their siblings produced significantly less PPF than control subjects. For both PPI and PPF, prepulse duration was not a significant factor. CONCLUSIONS: These results imply that PPF deficits reveal a generalized alerting or orienting deficit that is present in both schizophrenia patients and their siblings, suggesting that this deficit may be tapping an endophenotypic vulnerability factor.

Acoustic Stimulation↗

PubMed2004

Do the siblings of schizophrenia patients demonstrate affect perception deficits?

Affect perception deficits have been extensively documented in schizophrenia and are associated with the social dysfunction that is characteristic of this disorder. The two previous studies examined facial affect perception in genetically at-risk samples and yielded mixed results. The current study was designed to provide a rigorous test of affect perception abilities among schizophrenia patients (n=58), their biological siblings without psychosis (n=51), and nonpsychiatric controls (n=49). Participants completed three measures of affect perception, including facial, vocal, and combined modality. Schizophrenia patients performed significantly worse than controls on two of the three affect perception tests as well as a composite index based on all three tests. The performance of the sibling group fell between the patient and control groups on each of the affect perception tests. However, group differences achieved statistical significance only for the composite index with the siblings performing significantly worse than controls and significantly better than the schizophrenia group. These findings demonstrate that subtle deficits in affect perception are detectable in the unaffected siblings of schizophrenia patients when multiple measures of different types of affect perception abilities are used in combination.

Adult↗

PubMed2004

Review of cognition and brain structure in schizophrenia: profiles, longitudinal course, and effects of treatment.

Research on the cognitive and brain structural correlates of schizophrenia has seen tremendous progress over the past decade. It has become increasingly clear that there is no pathognomic neuropsychological or structural neuroanatomic profile in schizophrenia, likely due in part to etiological heterogeneity within the disorder. Nonetheless, several studies have indicated that verbal episodic memory and vigilance deficits are particularly prominent, and are observed even in untreated patients in their first episode of the disorder. The course of schizophrenia appears to be somewhat variable, and factors that contribute to the development of the illness, and in some patients, deterioration of cognitive functioning, have not been elucidated clearly. Neurodevelopmental factors, however, likely play an important role in the diathesis of the disorder, while neuropathological processes contribute to deterioration and progression. At this time, there are relatively few controlled comparisons of the cognitive effects of atypical and conventional antipsychotic medications. Additional studies of the potential effects of antipsychotic medications on structural brain abnormalities are warranted. It is hoped that newer innovative psychopharmacological approaches and neuropsychological remediation programs will, in the not-too-distant future, provide clinicians with a variety of means to improve the cognitive and social functioning of their patients.

Antipsychotic Agents↗

PubMed2004

Dynamic testing in schizophrenia: does training change the construct validity of a test?

Dynamic testing typically involves specific interventions for a test to assess the extent to which test performance can be modified, beyond level of baseline (static) performance. This study used a dynamic version of the Wisconsin Card Sorting Test (WCST) that is based on cognitive remediation techniques within a test-training-test procedure. From results of previous studies with schizophrenia patients, we concluded that the dynamic and static versions of the WCST should have different construct validity. This hypothesis was tested by examining the patterns of correlations with measures of executive functioning, secondary verbal memory, and verbal intelligence. Results demonstrated a specific construct validity of WCST dynamic (i.e., posttest) scores as an index of problem solving (Tower of Hanoi) and secondary verbal memory and learning (Auditory Verbal Learning Test), whereas the impact of general verbal capacity and selective attention (Verbal IQ, Stroop Test) was reduced. It is concluded that the construct validity of the test changes with dynamic administration and that this difference helps to explain why the dynamic version of the WCST predicts functional outcome better than the static version.

Cognition Disorders↗

PubMed2004

Cognitive functioning in schizophrenia: a consensus statement on its role in the definition and evaluation of effective treatments for the illness.

BACKGROUND: Truly effective treatments for schizophrenia require much more than clinical efficacy. Symptom improvement is all that is required to demonstrate clinical efficacy. However, for a treatment to be effective in a wide-ranging manner, improvement in various life domains, such as social functioning, independent living, and employment, should also be found. Thus, a much wider range of improvements, not widely produced by previous treatments, is required to take treatment for schizophrenia to a new level of effectiveness. CONSENSUS PROCESS: A teleconference consensus meeting was held with the bylined authors on December 10, 2002, to explore the factors that hinder the most effective treatments for schizophrenia. We argue that a possible unifying factor underlying these apparently disparate domains of effective treatment is cognitive functioning, which is impaired in people with schizophrenia. Treatment of cognitive dysfunction may have a central role in increasing the breadth of effective treatment for schizophrenia. CONCLUSIONS: Novel antipsychotics and specific cognitive-enhancing medications have preliminarily been shown to have cognitive benefits that might lead to broader effectiveness of treatments, eventually reflected in improvements in the daily lives of patients. These treatments may have their greatest impact when combined with focused psychological interventions. While the research to date does not provide a large number of successes, this area will be one of considerable research interest for the next decade, with developments likely to be very important to clinicians treating patients with schizophrenia.

Antipsychotic Agents↗

PubMed2003

Changes in cognitive functioning with risperidone and olanzapine treatment: a large-scale, double-blind, randomized study.

OBJECTIVE: The effects of risperidone and olanzapine on cognitive functioning in patients with schizophrenia were compared in a randomized, double-blind trial. METHOD: Three hundred and seventy-seven patients were randomly assigned to receive 2-6 mg/day of risperidone or 5-20 mg/day of olanzapine for 8 weeks. Cognitive function was assessed with a focused cognitive assessment battery; in addition, extrapyramidal symptoms were assessed using the extrapyramidal symptom rating scale (ESRS), and the positive and negative syndrome scale (PANSS) was rated for all patients. RESULTS: Treatment with these two atypical antipsychotic medications was associated with improved performance on the Wisconsin card sorting test, the trail-making test, the California verbal learning test, the continuous performance test, and some aspects of verbal fluency and spatial working memory. No differences in the effects of the drugs on any of the cognitive tests were noted. Correcting for the effects of anticholinergic treatment did not alter the magnitude of cognitive effects. CONCLUSIONS: Atypical antipsychotic treatment is associated with wide-ranging benefits on cognitive functioning. Previous reports of greater benefits of olanzapine over risperidone in a small-sample pilot study were not substantiated. These results are not due in general to changes in clinical symptoms or movement disorders, suggesting a direct effect of atypical antipsychotic medications on cognitive deficits in schizophrenia.

Adolescent↗

PubMed2003

Social perception and early visual processing in schizophrenia.

Persons with schizophrenia experience deficits in social cognition-the cognitive processes involved in how people perceive and interpret information about themselves, others, and social situations. These deficits may be related to the neurocognitive impairments often experienced by persons with schizophrenia. Our primary objective was to examine associations between social perception and early visual processing in schizophrenia. Our secondary objective was to examine whether outpatients with schizophrenia and healthy persons differ in social perception. Forty outpatients with schizophrenia and 30 healthy persons completed a measure of social perception (the Half-Profile of Nonverbal Sensitivity), visual masking procedures, and ratings of positive and negative symptoms. Within patients, performance on visual masking procedures was related to performance on the Half-Profile of Nonverbal Sensitivity. Patients with schizophrenia and the healthy persons differed significantly in their performance on the Half-Profile of Nonverbal Sensitivity, but this difference became nonsignificant when education was a covariate. These findings suggest that social perception in schizophrenia is related to very early aspects of visual processing.

Adult↗

PubMed2003

Lateralized lexical decision in schizophrenia: hemispheric specialization and interhemispheric lexicality priming.

Reports of left-hemisphere dysfunction and abnormal interhemispheric transfer in schizophrenia are mixed. The authors used a unified paradigm, the lateralized lexical decision task, to assess hemispheric specialization in word recognition, hemispheric error monitoring, and interhemispheric transfer in male, right-handed participants with schizophrenia (n=34) compared with controls (n=20). Overall, performance and error monitoring were worse in patients. However, patients like controls showed left-hemisphere superiority for lexical processing and right-hemisphere superiority for error monitoring. Only patients showed selective-interhemispheric lexicality priming for accuracy, in which performance improved when the lexical status of target and distractor stimuli presented to each hemifield was congruent. Results suggest that schizophrenia is associated with impaired monitoring and with increased interhemispheric automatic information transfer rather than with changed hemispheric specialization for language or error monitoring.

Adult↗

PubMed2003

Neuroanatomical correlates of formal thought disorder in schizophrenia.

INTRODUCTION: We attempted to extend findings of a relationship between formal thought disorder and left superior temporal gyrus (STG) volume in schizophrenia by examining two indices of formal thought disorder. METHODS: Three brain regions of interest were selected from magnetic resonance imaging slices in 15 young, right-handed, male schizophrenia patients: the STG, the anterior hippocampus, and the amygdala. Thought disorder was assessed using the Bizarre-Idiosyncratic Thinking (BIZ) scale, a sensitive measure of formal thought disorder based on responses to a standard set of stimuli, and the BPRS Conceptual Disorganization item, a global rating based on a clinical interview. RESULTS: BIZ ratings of thought disorder were significantly correlated with the left STG volume (Spearman r = -.73) and with the right STG volume (Spearman r = -.58). BIZ ratings were not significantly correlated with either the left or right anterior hippocampus or amygdala volumes. The BPRS Conceptual Disorganisation rating was not significantly related to the STG, anterior hippocampus, or amygdala volumes. CONCLUSIONS: This study confirms the previously reported association between the left STG and formal thought disorder, and suggests that detection of this relationship may be facilitated by use of highly sensitive formal thought disorder assessments.

Journal Article↗

PubMed2003

Neurocognitive assessment in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project schizophrenia trial: development, methodology, and rationale.

Patients with schizophrenia are severely impaired in crucial aspects of neurocognitive function. This impairment is the strongest clinical correlate of poor long-term outcome and adaptive dysfunction. Reports of neurocognitive enhancement with second generation antipsychotic medications have thus offered promise for improvement in the long-term outcome of patients with schizophrenia. However, the majority of these studies have had serious weaknesses in methodology, such as open-label design, small samples, or inappropriate dosing of medications. More recent studies have addressed these methodological issues but have been of short duration and have largely been sponsored by pharmaceutical companies. The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project is a unique opportunity to address the comparative neurocognitive effectiveness of available antipsychotic medications. This article describes the neurocognitive methods used in the schizophrenia trial of the CATIE project, including the selection and training of neurocognitive raters, patient inclusion criteria for assessment, rationale for the choice of neurocognitive instruments, and methodology for each neurocognitive test.

Antipsychotic Agents↗

PubMed2003

Is emotion processing a predictor of functional outcome in schizophrenia?

Deficits in the ability to perceive facial and vocal emotion expression are common in schizophrenia. However, relatively little is known about how such deficits might affect functional outcomes. This prospective study examined cross-sectional and longitudinal relationships between perception of emotion and aspects of psychosocial functioning, including family relationships, social relationships, work functioning, and independent living/self-care in 94 clinically stabilized schizophrenia outpatients from five community-based rehabilitation programs. Emotion perception (facial emotion, voice emotion, and affect perception) and psychosocial outcome (Strauss and Carpenter Outcome Scale and Role Functioning Scale) were assessed at baseline and after 12 months of psychosocial rehabilitation. Significant associations were found between perception of emotion and work functioning/independent living both cross-sectionally and prospectively over the 12 months. Causal explanatory models suggested that perception of emotion might cause work functioning/independent living outcome over 1 year. The results remained significant when conceptual disorganization was statistically controlled. We did not find differences between men and women in the correlations between emotion perception and work functioning/independent living. Associations between social functioning/family relationships and perception of emotion were not significant. These findings suggest that emotion processing is a key determinant of work functioning/independent living for individuals with serious mental illness.

Adult↗

PubMed2002

The neurocognitive effects of low-dose haloperidol: a two-year comparison with risperidone.

BACKGROUND: Neurocognitive deficits are core features of schizophrenia that are linked to functional outcome for the disorder. Recent studies and reviews have concluded that newer antipsychotic medications are better for neurocognitive deficits than conventional antipsychotic medications; however, one difficulty in interpreting this literature is that the comparisons have mainly been with high doses of conventional medications. This study examined the neurocognitive effects of low-dose haloperidol compared with risperidone over a 2-year period. METHODS: Sixty-two patients were randomly assigned to medication (starting at 6 mg of each medication) and administered neurocognitive batteries six times over the course of follow-up. At 6 months, the mean dose of haloperidol was 5.0 mg, and the mean dose of risperidone was 6.0 mg. Neurocognitive data were reduced into cluster scores and a global summary score. RESULTS: We found no significant overall differences in treatment effects on the cluster scores or the global score. The global score revealed a significant group by time interaction, reflecting the fact that the haloperidol group tended to improve initially and then stay stable, whereas the risperidone group improved more gradually over the follow-up period. CONCLUSIONS: This study did not provide support for neurocognitive advantages of a newer antipsychotic medication over a low-dose conventional medication. We speculate that conventional medications may have neurocognitive benefits at low doses that are neutralized or reversed at higher doses.

Adult↗