Biomedical subjects

Jose M Canive

Publications and source records attributed to Jose M Canive.

9 recordsLinked to original sources

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

Vector-based spatial-temporal minimum L1-norm solution for MEG.

Minimum L1-norm solutions have been used by many investigators to analyze MEG responses because they provide high spatial resolution images. However, conventional minimum L1-norm approaches suffer from instability in spatial construction, and poor smoothness of the reconstructed source time-courses. Activity commonly "jumps" from one grid point to (usually) the neighboring grid points. Equivalently, the time-course of one specific grid point can show substantial "spiky-looking" discontinuity. In the present study, we present a new vector-based spatial-temporal analysis using a L1-minimum-norm (VESTAL). This approach is based on a principle of MEG physics: the magnetic waveforms in sensor-space are linear functions of the source time-courses in the imaging-space. Our computer simulations showed that VESTAL provides good reconstruction of the source amplitude and orientation, with high stability and resolution in both the spatial and temporal domains. "Spiky-looking" discontinuity was not observed in the source time-courses. Importantly, the simulations also showed that VESTAL can resolve sources that are 100% correlated. We then examined the performance of VESTAL in the analysis of human median-nerve MEG responses. The results demonstrated that this method easily distinguishes sources very spatially close to each other, including individual primary somatosensory areas (BA 1, 2, 3b), primary motor area (BA 4), and other regions in the somatosensory system (e.g., BA 5, 7, SII, SMA, and temporal-parietal junction) with high temporal stability and resolution. VESTAL's potential for obtaining information on source extent was also examined.

Adult↗

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

Efficacy of olanzapine and risperidone in schizophrenia: a randomized double-blind crossover design.

This article compares the efficacy of olanzapine and risperidone for positive and negative symptoms using an 18-week, randomized, double-blind, crossover design. The hypotheses were that olanzapine would be more efficacious for treating negative symptoms, and that risperidone would be superior in treating positive symptoms. Positive and negative symptoms scores improved throughout treatment, regardless of medication type. Differences between the medications were found for negative and general psychopathology rating scales. Overall, olanzapine led to greater improvements in negative symptoms than did risperidone. When each scale was analyzed individually, greater improvements were found for olanzapine on Positive and Negative Symptoms Scale (PANSS) General,PANSS total, and Scale for the Assessment of Negative Symptoms (SANS)attention. A nearly significant trend favoring olanzapine was found for the Calgary Depression Scale. Several negative symptom subscales followed a nonsignificant trend toward olanzapine being more efficacious than risperidone.Thus, there was a very consistent pattern of greater efficacy for olanzapine, particularly for negative symptoms. Despite the small number of subjects, this study shows the potential of a within-subject design to elucidate differences in efficacy.

Adult↗

PubMed2005

A parietal-frontal network studied by somatosensory oddball MEG responses, and its cross-modal consistency.

Previous studies using functional magnetic resonance imaging (fMRI) and event-related potentials (ERPs) of the brain have found that a distributed parietal-frontal neuronal network is activated in normals during both auditory and visual oddball tasks. The common cortical regions in this network are inferior parietal lobule (IPL)/supramarginal gyrus (SMG), anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC). It is not clear whether the same network is activated by oddball tasks during somatosensory stimulation. The present study addressed this question by testing healthy adults as they performed a novel median-nerve oddball paradigm while undergoing magnetoencephalography (MEG). An automated multiple dipole analysis technique, the Multi-Start Spatio-Temporal (MSST) algorithm, localized multiple neuronal generators, and identified their time-courses. IPL/SMG, ACC, and DLPFC were reliably localized in the MEG median-nerve oddball responses, with IPL/SMG activation significantly preceding ACC and DLPFC activation. Thus, the same parietal-frontal neuronal network that shows activation during auditory and visual oddball tests is activated in a median-nerve oddball paradigm. Regions uniquely related to somatosensory oddball responses (e.g., primary and secondary somatosensory, dorsal premotor, primary motor, and supplementary motor areas) were also localized. Since the parietal-frontal network supports attentional allocation during performance of the task, this study may provide a novel method, as well as normative baseline data, for examining attention-related deficits in the somatosensory system of patients with neurological or psychiatric disorders.

Adult↗

PubMed2005

M50 sensory gating predicts negative symptoms in schizophrenia.

Impaired auditory sensory gating is considered characteristic of schizophrenia and a marker of the information processing deficit inherent to that disorder. Predominance of negative symptoms also reflects the degree of deficit in schizophrenia and is associated with poorer pre-morbid functioning, lower IQ, and poorer outcomes. However, a consistent relationship between auditory sensory gating and negative symptoms in schizophrenia has yet to be demonstrated. The absence of such a finding is surprising, since both impaired auditory gating and negative symptoms have been linked with impaired fronto-temporal cortical function. The present study measured auditory gating using the P50 event related potential (ERP) in a paired-click paradigm and capitalized on the relative localization advantage of magnetoencephalography (MEG) to assess auditory sensory gating in terms of the event related field (ERF) M50 source dipoles on bilateral superior temporal gyrus (STG). The primary hypothesis was that there would be a positive correlation between lateralized M50 auditory sensory gating measures and negative symptoms in patients with schizophrenia. A standard paired-click paradigm was used during simultaneous EEG and MEG data collection to determine S2/S1 sensory gating ratios in a group of 20 patients for both neuroimaging techniques. Participants were administered the Schedule for the Assessment of Negative Symptoms (SANS), the Positive and Negative Symptom Scale (PANSS), and the Calgary Depression Scale for Schizophrenia. Consistent with previous reports, there was no relationship between ERP P50 sensory gating and negative symptoms. However, right (not left) hemisphere ERF M50 sensory gating ratio was significantly and positively correlated with negative symptoms. This finding is compatible with information processing theories of negative symptoms and with more recent findings of fronto-temporal abnormality in patients with predominantly negative symptoms.

Adolescent↗

PubMed2003

The National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project: schizophrenia trial design and protocol development.

The National Institute of Mental Health initiated the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) program to evaluate the effectiveness of antipsychotic drugs in typical settings and populations so that the study results will be maximally useful in routine clinical situations. The CATIE schizophrenia trial blends features of efficacy studies and large, simple trials to create a pragmatic trial that will provide extensive information about antipsychotic drug effectiveness over at least 18 months. The protocol allows for subjects who receive a study drug that is not effective to receive subsequent treatments within the context of the study. Medication dosages are adjusted within a defined range according to clinical judgment. The primary outcome is all-cause treatment discontinuation because it represents an important clinical endpoint that reflects both clinician and patient judgments about efficacy and tolerability. Secondary outcomes include symptoms, side effects, neurocognitive functioning, and cost-effectiveness. Approximately 50 clinical sites across the United States are seeking to enroll a total of 1,500 persons with schizophrenia. Phase 1 is a double-blinded randomized clinical trial comparing treatment with the second generation antipsychotics olanzapine, quetiapine, risperidone, and ziprasidone to perphenazine, a midpotency first generation antipsychotic. If the initially assigned medication is not effective, subjects may choose one of the following phase 2 trials: (1) randomization to open-label clozapine or a double-blinded second generation drug that was available but not assigned in phase 1; or (2) double-blinded randomization to ziprasidone or another second generation drug that was available but not assigned in phase 1. If the phase 2 study drug is discontinued, subjects may enter phase 3, in which clinicians help subjects select an open-label treatment based on individuals' experiences in phases 1 and 2.

Adolescent↗

PubMed2002

Fluvoxamine treatment in veterans with combat-related post-traumatic stress disorder.

This study was designed to investigate the efficacy of the antidepressant fluvoxamine in the treatment of combat-related post-traumatic stress disorder (PTSD). Fifteen veterans with combat-related PTSD and no other psychiatric diagnosis except depression were recruited to participate in a 14-week open-label study of fluvoxamine. Patients underwent a 30-day washout period and were rated with the Clinician Administered PTSD Scale (CAPS), Mississippi Scale, Beck Depression Inventory (BDI), Hamilton Rating Scale for Depression (HAM-D) and Hamilton Rating Scale for Anxiety (HAM-A) at baseline, and every 2 weeks until week 14. Three patients stopped fluvoxamine prematurely due to side effects and 7 withdrew consent before completing the 14-week trial. Eight patients completed at least 8 weeks of treatment. The total daily dose of fluvoxamine ranged from 100 to 300 mg with a mean daily dose of 150 mg at week 14. Intent-to-treat analysis revealed a significant improvement in total CAPS scores, and in the intrusion and the avoidance/numbing subscales. The CAPS hyper-arousal scores did not change significantly. HAM-A score also improved significantly. No significant changes were seen on the Mississippi scale, HAM-D, or Beck Depression Inventory in the intent-to-treat analysis. In summary, our study shows that fluvoxamine appears to improve combat-related PTSD symptoms but not depressive symptoms. The high attrition rate and lack of a placebo group limits the conclusions of our study. Controlled studies of fluvoxamine in the treatment of PTSD are warranted.

Depression↗

PubMed2002

Abnormal stimulus-response intensity functions in posttraumatic stress disorder: an electrophysiological investigation.

OBJECTIVE: The purpose of this study was to explore the relationship between combat-related posttraumatic stress disorder (PTSD) and specific augmentation versus reduction patterns for the N100 and P200 components of auditory event-related potentials evoked by tones of increasing intensity. METHOD: Event-related potentials of subjects with PTSD (N=36), subjects with no psychopathology (N=20), subjects with major depression but no PTSD (N=10), and subjects with a history of chronic alcohol abuse but no PTSD (N=8) were recorded. Brain responses were evoked by a 2000-Hz tone presented in intensity blocks of 65, 72.5, 80, 87.5, and 95 dB (SPL). RESULTS: Evoked data from five PTSD subjects were of poor quality and excluded from further analyses. For all but one subject with no psychopathology and for all subjects with a history of alcohol abuse or major depression (but no PTSD), the Cz amplitude of the P200 response component showed augmentation as a nearly linear function of tone intensity. As a group, subjects with PTSD showed no such increase in P200 response magnitude. Examination of the data from individual subjects with PTSD showed that 42% exhibited augmentation patterns similar to those seen for subjects in the comparison groups. However, 58% showed evidence of P200 reduction, with the response to the loudest tone being smaller than responses to tones of intermediate intensity. CONCLUSIONS: The data suggest that there is a significant subgroup of patients with combat-related PTSD who enter into a state of protective inhibition at relatively low stimulus intensities. It is hypothesized that this is an appropriate adaptive mechanism for these subjects rather than an indication of a core neurobiological abnormality.

Acoustic Stimulation↗