Biomedical subjects

B G Bunney

Publications and source records attributed to B G Bunney.

8 recordsLinked to original sources

PubMed2000

Evidence for a compromised dorsolateral prefrontal cortical parallel circuit in schizophrenia.

Evidence is reviewed that one of the cognitive-affective parallel circuits in the brain, the dorsolateral prefrontal circuit, is compromised at the level of anatomical, neuropathological and transmitter-related molecules in a subgroup of schizophrenic patients. The dorsolateral prefrontal cortex (DLPFC) comprises a key structure in this circuit. Data supporting a compromised DLPFC includes cognitive deficits, decreased regional metabolism and blood flow activation; disruption of cortical subplate activity (inferred from maldistribution of neurons from the cortical subplate which are required for the orderly neuronal migration during the second trimester and for connectivity of the thalamocortical neurons); decrease in major components of the cortical inhibitory neurotransmitter system; and alterations in the molecules critical for NMDA-receptor mediated neural transmission. Thus a great deal of evidence accumulated over the last decade has definitively implicated the dorsolateral prefrontal cortex in the pathophysiology of schizophrenia. Emerging data also confirms neuropathology in the mediodorsal nucleus of the thalamus that projects to the DLPFC. There is currently a consensus that schizophrenia involves epigenetic factors interacting with genetic information in the cells to produce abnormal molecules which when they are associated with abnormal circuits such as the DLPFC, may result in abnormal behavior. Thus, abnormal cortical connections and or altered neurotransmitter related molecules in the DLPFC could explain some of the prominent frontal cognitive disruptions seen in schizophrenia.

Animals↗

PubMed2000

Molecular clock genes in man and lower animals: possible implications for circadian abnormalities in depression.

This paper reviews the recent discovery of clock genes that provide the mechanism for the regulation of circadian and seasonal rhythms in lower organisms and in humans and relates these clock genes to the circadian abnormalities in depression. (1) A subgroup of depressed patients have documented circadian abnormalities in mood, sleep, temperature and neuroendocrine secretion; (2) It is also suggested that seasonal affective disorder (SAD) patients may show an abnormality in their ability to shift their daily circadian rhythms in response to seasonal light changes; (3) The dramatic improvements in some depressions in response to three treatment modalities which manipulate circadian rhythms suggest that circadian abnormalities reported in patients may constitute a core component of the pathophysiology in depression; (4) Mutations in clock genes have been discovered that accelerate or delay circadian cycles; (5) It is hypothesized that 24-hour rhythm abnormalities in major depression and SAD may be due to altered clock genes.

Animals↗

PubMed1999

Structured Interview for Assessing Perceptual Anomalies (SIAPA).

Clinical descriptions of perceptual and attentional anomalies in schizophrenia emphasize phenomena such as flooding, or inundation, by sensory stimuli. A failure of sensory "gating" mechanisms in the brain is hypothesized to account for these symptoms, and this hypothesis has led to a marked interest in their putative psychophysiological substrates. However, there are no systematic analyses of the phenomenology of these perceptual experiences, nor has the hypothesized connection between the clinical phenomena and their reported psychophysiological substrates been tested. In this investigation, a structured interview instrument was developed to measure perceptual anomalies as distinct from hallucinations and to determine their prevalence across sensory modalities in schizophrenia in 67 schizophrenia subjects and 98 normal controls. The instrument includes Likert ratings of hypersensitivity, inundation, and selective attention to external sensory stimuli. Good interrater agreement, determined from interviews, was obtained. Schizophrenia subjects had significantly higher auditory, visual, and combined scores (i.e., across all modalities) than normal controls did, indicating significantly more perceptual anomalies. For the schizophrenia group, the prevalence of auditory and visual anomalies was significantly greater than the other sensory modalities. The data indicate that the putative phenomenological correlates of sensory gating may be reliably measured and tested with the Structured Interview for Assessing Perceptual Anomalies.

Adult↗

PubMed1999

Effect of clozapine and adjunctive high-dose glycine in treatment-resistant schizophrenia.

OBJECTIVE: The focus of this study was the systematic evaluation of the clinical effects of glycine as an adjunct to the atypical antipsychotic clozapine in the treatment of schizophrenia. METHOD: In a double-blind, placebo-controlled study, 19 patients with chronic, treatment-resistant schizophrenia who were maintained on optimal doses of clozapine (400-1200 mg/day) were administered either 30 g/day of glycine (N=9) or placebo (N=10) for 12 weeks. Clinical evaluations with the Brief Psychiatric Rating Scale, the Scale for the Assessment of Negative Symptoms, and the Simpson-Angus movement scale were completed biweekly. RESULTS: The use of glycine as an adjunct to clozapine was not effective in decreasing positive or negative symptoms. In contrast, the patients treated with clozapine without glycine had a 35% reduction in positive symptoms. CONCLUSIONS: These preliminary data suggest that glycine may interfere with the antipsychotic efficacy of atypical neuroleptics such as clozapine.

Adult↗

PubMed1997

Decreasing striatal 6-FDOPA uptake with increasing duration of cocaine withdrawal.

It has been hypothesized that a decrease in dopaminergic presynaptic activity during abstinence or withdrawal is related to relapse in cocaine-dependent subjects (Dackis and Gold 1985; Markou and Koob 1991). This study measured striatal 6-fluorodopa (6-FDOPA) uptake, an index of dopaminergic presynaptic activity, using positron emission tomography (PET) in 11 drug-free cocaine addicts compared to eight normal subjects. Middle abstinence cocaine addicts (n = 5, off cocaine 11-30 days) had significantly lower striatal 6-FDOPA uptake compared to normal controls or early abstinence cocaine addicts (n = 6, off cocaine 1-10 days). The cocaine-dependent subjects (n = 11) showed a significant negative correlation between days off cocaine and striatal 6-FDOPA uptake. The results suggest that during abstinence from cocaine there is a delayed decrease in dopamine terminal activity in the striatum.

Adult↗

PubMed1997

Shifting attention in visual space: tests of moving-spotlight models versus an activity-distribution model.

Participants were induced to concentrate preparatory attention at a central location, to identify a letter there, to identify a 2nd letter to the extreme left or right of a central horizontal range of 5 locations, and then to identify a 3rd letter at 1 of the central 5 locations. Analog and discrete versions of the moving-spotlight model predict that response times to the 3rd letter will be most rapid at the location of the 2nd letter, whereas an activity-distribution model predicts that the most rapid responses to the 3rd letter will be at the central location, where preparatory attention is strongest. The data from 3 experiments, taken together, are inconsistent with the moving-spotlight models and are consistent with the activity-distribution model.

Adult↗

PubMed1995

New morphological and neuropathological findings in schizophrenia: a neurodevelopmental perspective.

This article reviews evidence for morphological abnormalities in schizophrenia as assessed by brain imaging and neurohistochemical techniques including immunohistochemistry and in situ hybridization. Localized deficits in schizophrenic brain appear in many regions including frontal and temporal lobes, anterior cingulate, mediodorsal thalamic nucleus, and corpus callosum. These areas are interconnected and may provide the basis for a "psychosis circuitry." Neuronal disruption of elements in this circuitry may result in a hypothesized dysconnection syndrome. Evidence suggests an alteration in neuronal development related to either genetic and/or environmental factors. Primary and secondary anterograde and retrograde effects may accompany this neurodevelopmental defect and may further alter intrinsic and extrinsic neuronal communications. A number of studies are consistent with the second trimester of gestation being a critical period for fetal brain development, especially for neuronal migration. Fetal trauma due to environmental insults (e.g., influenza) during this trimester may increase the incidence of schizophrenia. Recent advances in the identification of factors that modulate neuronal development including axon guidance molecules, neurotrophins, and programmed cell death genes provide intriguing new areas for potential investigation. Future research may focus on the factors controlling neuronal migration and programmed cell death in the schizophrenic brain.

Autopsy↗

PubMedDate not supplied

Neuropathological studies of brain tissue in schizophrenia.

Postmortem neuropathological investigations in the last half decade provide increasing evidence compatible with a neurodevelopmental defect in schizophrenia. Basic and clinical data support hypotheses suggesting that disturbances in neurodevelopment in schizophrenia may involve the cortical subplate and a theorized second trimester "window of vulnerability". The focus of this paper is on (1) selected methodological issues involved in the collection, analyses and preservation of human postmortem brain tissue; (2) a review of evidence showing morphological defects particularly in prefrontal cortical regions of the schizophrenic brain; and (3) potential future research directions.

Brain↗