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Biomedical subjects

Jeffrey A Lieberman

Publications and source records attributed to Jeffrey A Lieberman.

At least 37 records · Page 2Linked to original sources
PubMed2006

Electrophysiological indices of automatic and controlled auditory information processing in first-episode, recent-onset and chronic schizophrenia.

BACKGROUND: Deficits in amplitudes of auditory event-related potentials (ERP) indexing preattentive, automatic (mismatch negativity, MMN) and controlled, attention-dependent (N2, P3) auditory information processing have been well described in chronic schizophrenia. Normal MMN, but deficient N2 and P3 have been reported in first-episode patients. No study has investigated these ERPs concurrently in first-episode patients; thus, reported differences in MMN, N2 and P3 generation may reflect differences in patient samples rather than genuine differences in abnormal generation of these ERPs. METHODS: We recorded MMN, N2 and P3 in 26 first-episode patients, 25 recent-onset patients within 1.5 to 5 years after first admission, 25 chronic patients and 39 healthy controls. RESULTS: Recent-onset and chronic, but not first-episode patients showed reduced MMN. However, among first-episode patients those with low premorbid educational achievement demonstrated significantly reduced MMN. All patient groups showed pronounced N2 deficits and, to a variable extent, abnormalities in P3 generation. CONCLUSIONS: Abnormalities in N2 and P3 generation appear to reflect premorbid neuropathology, whereas MMN deficits may index both ongoing disease processes associated with illness progression as well as premorbid neurocognitive impairment. ERPs may provide tools to assess static and progressive neuropathology in schizophrenia. These findings need confirmation in longitudinal studies.

Acoustic Stimulation↗
PubMed2006

A national study of violent behavior in persons with schizophrenia.

CONTEXT: Violent behavior is uncommon, yet problematic, among schizophrenia patients. The complex effects of clinical, interpersonal, and social-environmental risk factors for violence in this population are poorly understood. OBJECTIVE: To examine the prevalence and correlates of violence among schizophrenia patients living in the community by developing multivariable statistical models to assess the net effects of psychotic symptoms and other risk factors for minor and serious violence. DESIGN: A total of 1410 schizophrenia patients were clinically assessed and interviewed about violent behavior in the past 6 months. Data comprise baseline assessments of patients enrolled in the National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness. SETTING AND PATIENTS: Adult patients diagnosed as having schizophrenia were enrolled from 56 sites in the United States, including academic medical centers and community providers. MAIN OUTCOME MEASURES: Violence was classified at 2 severity levels: minor violence, corresponding to simple assault without injury or weapon use; and serious violence, corresponding to assault resulting in injury or involving use of a lethal weapon, threat with a lethal weapon in hand, or sexual assault. A composite measure of any violence was also analyzed. RESULTS: The 6-month prevalence of any violence was 19.1%, with 3.6% of participants reporting serious violent behavior. Distinct, but overlapping, sets of risk factors were associated with minor and serious violence. "Positive" psychotic symptoms, such as persecutory ideation, increased the risk of minor and serious violence, while "negative" psychotic symptoms, such as social withdrawal, lowered the risk of serious violence. Minor violence was associated with co-occurring substance abuse and interpersonal and social factors. Serious violence was associated with psychotic and depressive symptoms, childhood conduct problems, and victimization. CONCLUSIONS: Particular clusters of symptoms may increase or decrease violence risk in schizophrenia patients. Violence risk assessment and management in community-based treatment should focus on combinations of clinical and nonclinical risk factors.

Adult↗
PubMed2006

Single-voxel 1H PRESS at 4.0 T: precision and variability of measurements in anterior cingulate and hippocampus.

The precision [coefficient of variation or CV (%) = 100SD/X] of single-voxel point resolved spectroscopic data was characterized bilaterally, in anterior cingulate and in hippocampus, at 4.0 T in a healthy subject. Data acquisition was replicated 10 times after voxel repositioning and readjusting higher order shims. Precision measurements show that the scan-to-scan precision is better in anterior cingulate than in hippocampus, with an average CV of 9.2% (for total NAA, tCho and Cr) in anterior cingulate and 13.9% in hippocampus. Variability measurements made by the same method in 24 healthy subjects and in 29 schizophrenia patients showed that there is substantial biological variability in metabolite levels, even in healthy subjects. Simple calculations suggest that more than 200 subjects would be needed to detect a 5% difference in NAA between patients and controls.

Adult↗
PubMed2006

Clinical trials for antipsychotic drugs: design conventions, dilemmas and innovations.

More than 50 years after the introduction of modern pharmacotherapies for schizophrenia, there remains a tremendous need for therapeutic advances. A second generation of antipsychotic drugs, introduced over the past 15 years, has provided uncertain advantages over the first-generation drugs. This paper reviews the designs of studies that evaluate the effectiveness of putative antipsychotic drugs. Data from the trials needed to achieve regulatory approval do not meet all the needs of clinicians and policy makers. Practical and large, simple trials that evaluate the comparative effectiveness of antipsychotic drugs in real-world settings can help to meet these needs once a drug has reached the market.

Antipsychotic Agents↗
PubMed2006

Neuroactive steroids are altered in schizophrenia and bipolar disorder: relevance to pathophysiology and therapeutics.

Evidence suggests that neuroactive steroids may be candidate modulators of schizophrenia pathophysiology and therapeutics. We therefore investigated neuroactive steroid levels in post-mortem brain tissue from subjects with schizophrenia, bipolar disorder, nonpsychotic depression, and control subjects to determine if neuroactive steroids are altered in these disorders. Posterior cingulate and parietal cortex tissue from the Stanley Foundation Neuropathology Consortium collection was analyzed for neuroactive steroids by negative ion chemical ionization gas chromatography/mass spectrometry preceded by high-performance liquid chromatography. Subjects with schizophrenia, bipolar disorder, nonpsychotic depression, and control subjects were group matched for age, sex, ethnicity, brain pH, and post-mortem interval (n = 14-15 per group, 59-60 subjects total). Statistical analyses were performed by ANOVA with post-hoc Dunnett tests on log transformed neuroactive steroid levels. Pregnenolone and allopregnanolone were present in human post-mortem brain tissue at considerably higher concentrations than typically observed in serum or plasma. Pregnenolone and dehydroepiandrosterone levels were higher in subjects with schizophrenia and bipolar disorder compared to control subjects in both posterior cingulate and parietal cortex. Allopregnanolone levels tended to be decreased in parietal cortex in subjects with schizophrenia compared to control subjects. Neuroactive steroids are present in human post-mortem brain tissue at physiologically relevant concentrations and altered in subjects with schizophrenia and bipolar disorder. A number of neuroactive steroids act at inhibitory GABA(A) and excitatory NMDA receptors and demonstrate neuroprotective and neurotrophic effects. Neuroactive steroids may therefore be candidate modulators of the pathophysiology of schizophrenia and bipolar disorder, and relevant to the treatment of these disorders.

Analysis of Variance↗
PubMed2006

Cognitive development in schizophrenia: follow-back from the first episode.

Despite consensus that schizophrenia is a neurodevelopmental disorder characterized by cognitive deficits, objective data documenting the course of cognitive development remain sparse. We conducted a follow-back study of patients ascertained at the time of their initial episode of schizophrenia or schizoaffective disorder, and a group of demographically matched healthy volunteers. We obtained school records containing standardized achievement test scores from the 1st through 12th grades, and scholastic aptitude test results from the 11th and 12th grades, and examined the developmental trajectories of cognitive performance with respect to prospective examinations conducted following participants' enrollment in our study. We found significant differences in academic achievement tests as early as the first grade, with scores from participants who would later develop schizophrenia lagging behind their peers by 0.8 to 1.1 grade equivalents. This gap widened resulting in a difference between groups of 1.5 to 1.8 grade equivalents by the 12th grade. In the subset of patients for whom SAT scores were available, we found that WAIS-R Full Scale IQ was 11.5 points lower than predicted from earlier SAT scores, suggesting a substantial decline in cognitive ability accompanying the initial episode of illness. These findings suggest that schizophrenia is marked by substantial cognitive deficits in the first grade, that there may be additional subtle decline preceding the overt onset of psychotic symptoms, and that the initial episode of illness is marked by additional decline. These observations may help advance concepts of premorbid cognitive ability in the schizophrenia syndrome and constrain models of pathophysiology.

Adolescent↗
PubMed2006

Substance use in persons with schizophrenia: baseline prevalence and correlates from the NIMH CATIE study.

This study examined baseline correlates of substance use in the NIMH Clinical Antipsychotic Trials of Intervention Effectiveness project. Approximately 60% of the sample was found to use substances, including 37% with current evidence of substance use disorders. Users (with and without substance use disorders), compared with nonusers, were significantly more likely to be male, be African-American, have lower educational attainment, have a recent period of homelessness, report more childhood conduct problems, have a history of major depression, have lower negative symptom and higher positive symptom scores on the Positive and Negative Syndrome Scale, and have a recent illness exacerbation. Individuals with comorbid substance use disorders were significantly more likely to be male, report more childhood conduct problems, have higher positive symptom scores on the Positive and Negative Syndrome Scale, and have a recent illness exacerbation. These analyses suggest that substance use disorders in schizophrenia are especially common among men with a history of childhood conduct disorder problems and that childhood conduct disorder problems are potent risk factors for substance use disorders in schizophrenia.

Antipsychotic Agents↗
PubMed2006

Effectiveness of switching antipsychotic medications.

OBJECTIVE: Changing antipsychotics is common despite the dearth of information on risks and benefits associated with medication changes. The authors examined phase 1 findings from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study to explore whether it was more advantageous to continue taking the medication being received at baseline or to switch to a different antipsychotic. METHOD: First, for patients randomly assigned to treatment with olanzapine (N=314) or risperidone (N=321), the authors assessed the impact of being assigned to stay with the medication they were receiving at entry into the study versus being assigned to switch to these medications from a different antipsychotic. Second, for patients whose baseline antipsychotic was olanzapine (N=319), risperidone (N=271), or quetiapine (N=94), the authors examined the impact of being randomly assigned to stay with the same antipsychotic versus switch. Finally, the authors assessed the impact of removing the data of 209 patients whose random assignment was to stay with their baseline antipsychotic. The authors followed analysis strategies for CATIE; primary outcome was time until all-cause treatment discontinuation. RESULTS: Individuals randomly assigned to olanzapine and risperidone who were continuing with their baseline medication had significantly longer times until discontinuation than did those assigned to switch antipsychotics. When these "stayers" were removed, differences seen in the original CATIE phase 1 analyses were attenuated, although the original pattern of results remained. CONCLUSIONS: Comparisons of medication effectiveness should take into account whether medications being compared were each newly initiated. Further, unless the clinical situation requires a medication change, prescribers may want to take steps to optimize current medication regimens (e.g., dosage adjustments, behavioral or psychosocial interventions) before switching medications.

Adolescent↗
PubMed2006

Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment.

OBJECTIVE: When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug, it is unclear what other antipsychotic to switch to and when to use clozapine. In this study, the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness (CATIE) investigation. METHOD: Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone in phase 1 or 1B of the trials, primarily because of inadequate efficacy, were randomly assigned to open-label treatment with clozapine (N=49) or blinded treatment with another newer atypical antipsychotic not previously received in the trial (olanzapine [N=19], quetiapine [N=15], or risperidone [N=16]). RESULTS: Time until treatment discontinuation for any reason was significantly longer for clozapine (median=10.5 months) than for quetiapine (median=3.3), or risperidone (median=2.8), but not for olanzapine (median=2.7). Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine, quetiapine, or risperidone. At 3-month assessments, Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine. One patient treated with clozapine developed agranulocytosis, and another developed eosinophilia; both required treatment discontinuation. CONCLUSIONS: For these patients with schizophrenia who prospectively failed to improve with an atypical antipsychotic, clozapine was more effective than switching to another newer atypical antipsychotic. Safety monitoring is necessary to detect and manage clozapine's serious side effects.

Adult↗
PubMed2006

Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic.

BACKGROUND: In the treatment of schizophrenia, changing antipsychotics is common when one treatment is suboptimally effective, but the relative effectiveness of drugs used in this strategy is unknown. This randomized, double-blind study compared olanzapine, quetiapine, risperidone, and ziprasidone in patients who had just discontinued a different atypical antipsychotic. METHOD: Subjects with schizophrenia (N=444) who had discontinued the atypical antipsychotic randomly assigned during phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) investigation were randomly reassigned to double-blind treatment with a different antipsychotic (olanzapine, 7.5-30 mg/day [N=66]; quetiapine, 200-800 mg/day [N=63]; risperidone, 1.5-6.0 mg/day [N=69]; or ziprasidone, 40-160 mg/day [N=135]). The primary aim was to determine if there were differences between these four treatments in effectiveness measured by time until discontinuation for any reason. RESULTS: The time to treatment discontinuation was longer for patients treated with risperidone (median: 7.0 months) and olanzapine (6.3 months) than with quetiapine (4.0 months) and ziprasidone (2.8 months). Among patients who discontinued their previous antipsychotic because of inefficacy (N=184), olanzapine was more effective than quetiapine and ziprasidone, and risperidone was more effective than quetiapine. There were no significant differences between antipsychotics among those who discontinued their previous treatment because of intolerability (N=168). CONCLUSIONS: Among this group of patients with chronic schizophrenia who had just discontinued treatment with an atypical antipsychotic, risperidone and olanzapine were more effective than quetiapine and ziprasidone as reflected by longer time until discontinuation for any reason.

Adult↗
PubMed2006

Aggression and quantitative MRI measures of caudate in patients with chronic schizophrenia or schizoaffective disorder.

Caudate dysfunction is implicated in schizophrenia. However, little is known about the relationship between aggression and caudate volumes. Forty-nine patients received magnetic resonance imaging scanning in a double-blind treatment study in which aggression was measured. Caudate volumes were computed using a semiautomated method. The authors measured aggression with the Overt Aggression Scale and the Positive and Negative Syndrome Scale. Larger caudate volumes were associated with greater levels of aggression. The relationship between aggression and caudate volumes may be related to the iatrogenic effects of long-term treatment with typical antipsychotic agents or to a direct effect of schizophrenic processes on the caudate.

Adult↗
PubMed2006

Interrelationships of psychiatric symptom severity, medical comorbidity, and functioning in schizophrenia.

OBJECTIVE: This cross-sectional study aimed to evaluate the interrelationships of psychiatric symptom severity, medical comorbidity, and psychosocial functioning in a sample of patients with schizophrenia by utilizing the baseline data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). METHODS: This study utilized baseline data from a multisite trial of antipsychotic pharmacotherapy, which collected data from 1,460 patients with schizophrenia at more than 50 sites in the United States between 2001 and 2003. Bivariate correlations were used to evaluate associations between schizophrenia symptoms and medical comorbidity, and multivariate regression models were used to determine the independent association between medical comorbidity and psychosocial functioning. RESULTS: Of the 1,424 participants in the study sample, 58 percent had at least one medical condition: 20 percent had hypertension, 11 percent had diabetes mellitus, and 9 percent had four or more medical conditions. Medical comorbidity was associated with poorer neurocognitive functioning and greater depressive symptoms. The number of medical conditions was not associated with more severe schizophrenia symptoms. Both the number of medical conditions and physical health status were only weak correlates of psychosocial functioning. CONCLUSIONS: In this sample of persons with schizophrenia, medical comorbidity was associated with depression and neurocognitive impairment but was a weaker correlate of psychosocial functioning or employment status than psychotic symptoms, depression, and neurocognitive impairment.

Adolescent↗
PubMed2006

Substance use and psychosocial functioning in schizophrenia among new enrollees in the NIMH CATIE study.

OBJECTIVE: This study examined the relationship between substance use and psychosocial functioning in schizophrenia. METHODS: Participants were enrolled in the Clinical Antipsychotic Trials of Intervention Effectiveness. This study used baseline assessments and examined psychosocial functioning assessed by the Quality of Life Scale. Participants were classified as being abstinent, using substances, or having a substance use disorder. RESULTS: Of the 1,460 participants, 23 percent used substances and 37 percent had a substance use disorder. Of the 544 with a substance use disorder, 87 percent used alcohol, 44 percent used marijuana, and 36 percent used cocaine. Compared with participants who used substances, those with a substance use disorder had higher rates of polysubstance use. Compared with those who were abstinent, those who used substances had higher overall psychosocial functioning, and those with a substance use disorder had similar overall functioning but lower scores on the common objects and activities subscales. Among participants with a substance use disorder, those who used cocaine had lower overall functioning. CONCLUSIONS: Compared with abstinence, substance use and substance use disorder, unless they involved cocaine use, were generally associated with higher or equivalent overall psychosocial functioning. Patterns of substance use were similar to those in the community, suggesting that treatment of substance use disorders in schizophrenia should focus on reconnecting substance users to nonusing peer groups.

Adult↗
PubMed2006

Components and correlates of family burden in schizophrenia.

OBJECTIVE: Components and correlates of caregiver burden in schizophrenia were studied. METHODS: The family caregivers of 623 (43 percent) of 1,460 patients with schizophrenia enrolled in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) were interviewed about resources they provided and experiences with patient behavior over the previous month. Patients were independently evaluated on symptoms, quality of life, neurocognition, medication side effects, and service use. Factor analysis reduced the caregiver data into four orthogonal factors assessing perceptions of patient problem behavior, patient impairment in activities of daily living, patient helpfulness, and resource demands and disruptions in the caregiver's personal routine. RESULTS: Hierarchical regression analyses demonstrated differential correlates of burden for each factor, explaining 34 percent of variance each for problem behavior and resource demands and disruption, 21 percent for impairment in activities of daily living, and 38 percent for patient helpfulness. Demographic characteristics and patient symptoms explained the greatest proportion of variance, whereas quality of life and service use explained modest variance and patient neurocognition and medication side effects were not significantly associated with burden. CONCLUSIONS: Results underscore the need for continued intervention with family members after the acute inpatient phase of treatment to address the impacts of symptoms as well as incorporation of skills training into consumer treatment programs to improve consumer contributions to household maintenance.

Adult↗