Biomedical subjects

David L Copolov

Publications and source records attributed to David L Copolov.

9 recordsLinked to original sources

PubMed2006

Olfactory sensitivity through the course of psychosis: Relationships to olfactory identification, symptomatology and the schizophrenia odour.

There is some evidence for an unusual body odour in schizophrenia that has been linked to a hexenoic acid derivative (trans-3-methyl-2-hexenoic acid; MHA). Poor body odour has been linked to increased negative symptoms and reduced olfactory identification ability. However, the relationship between these findings and MHA, including olfactory sensitivity for MHA, has not been examined. Olfactory sensitivity thresholds were assessed for MHA and n-butyl-alcohol (NBA), in normal controls (CTL; n=24), patients with chronic schizophrenia (CHR; n=32) and a first-episode psychosis cohort (FE; n=31). In addition, forced choice detection of the pheromonal steroids 5-alpha-androst-16-en-3-one, androsterone-sulphate and estrone-3-sulphate was performed along with a measure of olfactory identification. CHR patients had significantly reduced sensitivity to MHA, but not NBA, compared to FE and CTL subjects. While sensitivity to pheromones was not different between the groups, CHR patients who could not detect them also showed poorer sensitivity to MHA. Further, the CHR group showed a significant association between reduced MHA sensitivity and greater levels of disorganised and negative symptoms. No relationships between identification and sensitivity for any substance were found. Our findings are the first to report reduced sensitivity for MHA in chronic schizophrenia patients, in the absence of similar impairment for more traditionally used substances. This may be linked to olfactory habituation effects, abnormal chemical processing or a genetic predisposition.

1-Butanol↗

PubMed2004

Correlates of the affective impact of auditory hallucinations in psychotic disorders.

While many who hear auditory hallucinations (AHs) experience them as unpleasant, some do not. Little is known about the correlates of AHs that are not unpleasant, or of the characteristics of those who hear them. To better understand this symptom, we used a comprehensive structured interview schedule to study 199 subjects who had experienced AHs. Subjects' responses to AHs were combined into two indexes: one assessing total affective impact and the other assessing the affective direction (positive or negative). Subjects who had grandiose delusions experienced their AHs more positively. AHs that were more frequent, lasted longer, and were louder were experienced more negatively. AHs heard in the second person and those related to people with whom the subjects had personal relationships were more positive than those heard in the third person. Many other aspects of AHs were unrelated to total affective impact or direction. It is argued that the positive evaluation of voices by subjects requires greater attention than it has received previously. Implications for assessment, clinical practice, and research are discussed.

Adolescent↗

PubMed2004

Factors associated with compliance and resistance to command hallucinations.

Command hallucinations (CHs) are hallucinations that direct the patient to perform an action. Beyond issues related to the danger that some CHs may pose, comparatively little is known about the broader clinical context of CHs. To investigate this, 199 patients were interviewed using the Mental Health Research Institute Unusual Perceptions Scale. More than two thirds of the sample reported hearing CHs. A quarter of these patients felt unable to resist them. Patients with CHs reported their voices more negatively than those who did not hear commands. More of those unable to resist CHs rated their hallucinations as intrusive, they had fewer coping strategies than those able to resist, and they were prescribed higher dosages of medication. CHs are associated with a greater degree of adverse hallucinatory and illness experience. Patients who experience CHs may have a more malignant form of the underlying disorder. Thus, CHs warrant special therapeutic attention for reasons beyond any harm that their commands pose to themselves or others.

Adaptation, Psychological↗

PubMed2003

Cortical activation associated with the experience of auditory hallucinations and perception of human speech in schizophrenia: a PET correlation study.

A [H(2)(15)O] PET correlation analysis technique was employed to correlate brain activations associated with self-reports of auditory hallucinations in hallucinating patients (n=8) and perception of transient, random human speech in non-hallucinating (n=7) patients and normal control subjects (n=8). Perception of externally generated human speech amongst the non-hallucinating and normal control participants was associated with a consistent pattern of extensive bilateral auditory cortex activation (Brodmann areas 40/41/42/22). Hallucinating participants demonstrated a network of cortical activations including bilateral auditory cortex, left limbic regions, right medial frontal and right prefrontal regions. The observed pattern of activation is consistent with models of auditory hallucinations as mis-remembered episodic memories of speech.

Adult↗

PubMed2003

Differential role of serotonergic projections arising from the dorsal and median raphe nuclei in locomotor hyperactivity and prepulse inhibition.

While an involvement of brain serotonin systems in schizophrenia has been suggested by many studies, the relative role of different serotonergic projections in the brain remains unclear. We therefore examined the effects of selective brain serotonin depletion on psychotropic drug-induced locomotor hyperactivity and prepulse inhibition, two animal models of aspects of schizophrenia. Pentobarbital-anesthetized (60 mg/kg, i.p.) male Sprague-Dawley rats were stereotaxically microinjected with 1 microl of a 5 microg/microl solution of the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) into either the dorsal or median raphe nucleus. At 2 weeks after the surgery, rats with dorsal raphe lesions did not show changes in psychotropic drug-induced locomotor hyperactivity, but displayed partial disruption of prepulse inhibition. In contrast, rats with median raphe lesions showed significant enhancement of phencyclidine-induced, but not amphetamine-induced locomotor hyperactivity and a marked disruption of prepulse inhibition. These results provide evidence for differential involvement of serotonergic projections in locomotor hyperactivity and prepulse inhibition. This study may help to explain the role of different serotonin projections in the brain in the pathophysiology of schizophrenia.

5,7-Dihydroxytryptamine↗

PubMed2003

Impairment of olfactory identification ability in individuals at ultra-high risk for psychosis who later develop schizophrenia.

OBJECTIVE: Previous investigation has revealed stable olfactory identification deficits in neuroleptic-naive patients experiencing a first episode of psychosis, but it is unknown if these deficits predate illness onset. METHOD: The olfactory identification ability of 81 patients at ultra-high risk for psychosis was examined in relation to that of 31 healthy comparison subjects. Twenty-two of the ultra-high-risk patients (27.2%) later became psychotic, and 12 of these were diagnosed with a schizophrenia spectrum disorder. RESULTS: There was a significant impairment in olfactory identification ability in the ultra-high-risk group that later developed a schizophrenia spectrum disorder but not in any other group. CONCLUSIONS: These findings suggest that impairment of olfactory identification is a premorbid marker of transition to schizophrenia, but it is not predictive of psychotic illness more generally.

Adolescent↗

PubMed2002

Paracingulate morphologic differences in males with established schizophrenia: a magnetic resonance imaging morphometric study.

BACKGROUND: Our previous work on sulcal-gyral brain morphology in healthy volunteers revealed that males were characterized by greater cortical folding in the left versus right anterior cingulate cortex. Given the evidence showing an absence or reversal of normal anatomical asymmetries in patients with schizophrenia, the current study examined the anterior cingulate cortex sulcal-gyral patterns in patients with schizophrenia. METHODS: Using high-resolution magnetic resonance imaging, we examined anterior cingulate cortex surface morphology in a group of 55 patients with established schizophrenia and 75 healthy controls. All subjects were male and right-handed. Depending on the presence of a paracingulate sulcus and its antero-posterior extent, three types of anterior cingulate cortex sulcal patterns were identified: "prominent," "present," and "absent." Measures of overall cerebral hemispheric folding were used as independent variables and as covariates to ascertain the specificity of the findings to the anterior cingulate cortex. RESULTS: Examination of anterior cingulate cortex morphology showed that, compared with controls, patients with schizophrenia lacked the leftward anterior cingulate cortex sulcal asymmetry, which was explained by reduced folding in the left anterior cingulate cortex. These differences were over and above differences in cortical folding across the entire left hemisphere. CONCLUSIONS: These findings suggest that, in male patients with schizophrenia, there is a disturbance in the neurodevelopment of the left anterior cingulate cortex, as well as a more general aberration of left hemisphere development.

Adult↗

PubMed2002

High-resolution phosphor imaging: validation for use with human brain tissue sections to determine the affinity and density of radioligand binding.

This study investigated the suitability of high-resolution storage phosphor imaging for the quantitative analysis of radioligand binding to human brain tissue. Hence, the binding of [(3)H]mazindol to the dopamine transporter in caudate-putamen tissue homogenates or frozen tissue sections apposed to either autoradiographic film or phosphor imaging plates was measured. Estimates of binding affinity were similar for homogenate studies and phosphor imaging plates (Kd=6.44+/-0.14 and 6.91+/-0.47 nM, respectively), but higher values were obtained with film autoradiography (Kd=11.31+/-0.82 nM). The density of binding was similar for both autoradiographic techniques (Bmax=371.9+/-30.8 fmol/mg estimated tissue equivalent, ETE (imaging plate) and 425+/-13.77 fmol/mg ETE (film)), although lower values were obtained from tissue homogenates (Bmax=64.27+/-6.74 fmol/mg wet weight). These results suggest that high resolution phosphor imaging can be used to analyse radioligand binding parameters in human brain tissue. Moreover, the reduced exposure time of phosphor imaging plates (e.g. 7 days vs 5 weeks) allows results to be obtained more rapidly than with conventional film autoradiography.

Adult↗

PubMed2002

Psychiatry.

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Australia↗