Biomedical subjects

Peter F Liddle

Publications and source records attributed to Peter F Liddle.

10 recordsLinked to original sources

PubMed2003

Influence of antipsychotic agents on neurological soft signs and dyskinesia in first episode psychosis.

First episode psychosis patients treated with atypical antipsychotics had significantly fewer signs of dyskinesia than patients treated with classical antipsychotics, but there were no significant differences regarding the total number of neurological soft signs (NSS). This suggests that the type of antipsychotic medication does not influence NSS, but that atypical antipsychotics are associated with less dyskinesia in the early stages of treatment.

Adult↗

PubMed2003

Methodological considerations regarding the association of Stroop and verbal fluency performance with the symptoms of schizophrenia.

Previous research on schizophrenia has reported conflicting findings regarding the association between Stroop performance and the disorganization syndrome, as well as performance on verbal fluency tests and the psychomotor poverty syndrome. In the present work, we consider whether these inconsistencies may be increased due to variations in test format and failures to report the appropriate test parameters. In 36 schizophrenic inpatients, we administered list and single-trial versions of the Stroop test, and report the correlation with the disorganization syndrome for both errors and speed. For verbal fluency, we separated the total score into measures of switching and clustering, and observed the relationship with psychomotor poverty. For both versions of the Stroop test, accuracy, but not speed, was correlated with disorganization. For verbal fluency, decreased cluster production relative to total words generated was associated with psychomotor poverty, but the number of switches between clusters was not. It is suggested that assessing and reporting a full range of test parameters can reduce between-study inconsistencies. Cognitive interpretations for the present set of results are discussed.

Adult↗

PubMed2003

Reproducibility of the hemodynamic response to auditory oddball stimuli: a six-week test-retest study.

Determining the reliability and reproducibility of the hemodynamic response is important for the interpretation and understanding of the results of functional magnetic resonance imaging (fMRI) experiments. We describe a whole brain fMRI study designed to examine the reproducibility of the event-related hemodynamic response elicited by low-probability task-relevant target stimuli and low-probability task-irrelevant novel stimuli assessed 6 weeks apart. Reliable activation was observed during test and retest for processing of target stimuli in multiple frontal, temporal, parietal, cerebellar, and subcortical sites. Novel stimuli elicited reliable activation during test and retest in lateral frontal cortex, inferior parietal lobule, and lateral temporal cortex, though there was evidence of habituation at some cortical sites. The patterns of activation associated with target detection and novelty processing are consistent with the intracranial distribution of the neural sources generated during similar tasks and replicate the results of previous event-related fMRI studies. The observed pattern of results supports the hypothesis that the hemodynamic response to target and novel stimuli is highly reproducible over the 6-week test-retest period.

Acoustic Stimulation↗

PubMed2003

Rostral anterior cingulate cortex dysfunction during error processing in schizophrenia.

Previous research has demonstrated that patients with schizophrenia have an impaired ability to monitor erroneous responses to stimuli internally. Event-related potential (ERP) studies of error-eliciting tasks indicate that, in healthy adults, the commission of an erroneous response is associated with a fronto-centrally distributed negative voltage component termed the error negativity (Ne) or error-related negativity (ERN). In patients with schizophrenia, the Ne/ERN elicited by errors of commission (EoC) is reduced in amplitude compared with that elicited in healthy participants. Functional MRI (fMRI) studies and source localization analyses of ERP data in healthy participants suggest that EoC are associated with activity in the rostral anterior cingulate cortex (ACC). Using event-related fMRI, we examined the brain activity associated with EoC in a group of 10 patients with schizophrenia and 16 matched healthy participants. Patients were stable, partially remitted, medicated out-patients recruited from the community. Participants performed a Go/NoGo task variant that was shown previously to elicit a reduced Ne/ERN during EoC in patients with schizophrenia relative to healthy participants, as well as robust rostral ACC activation during EoC in healthy participants. Patients with schizophrenia were characterized by relative underactivity in the rostral ACC compared with healthy participants. There was also evidence for more widespread underactivity in the limbic system. In contrast to these regions of relative hypoactivity, patients with schizophrenia demonstrated hyperactivity relative to healthy participants in bilateral parietal cortex during both EoC and correctly rejected NoGo trials. Our results are consistent with previous ERP research demonstrating functional abnormalities during error processing in schizophrenia. In light of the role of the rostral ACC and other limbic structures in mediating affective and motivational behaviour, our results suggest there may be a disturbed affective or motivational response to the commission of errors in schizophrenia.

Adult↗

PubMed2002

Error-related negativity and correct response negativity in schizophrenia.

OBJECTIVES: To examine error-related negativity (ERN) and correct response negativity (CRN) in schizophrenia in light of two previous conflicting reports, and to determine their relation to disorganization, psychomotor poverty and reality distortion. METHODS: Event-related potentials were recorded from 21 schizophrenic and 21 control participants who performed a simple go/no-go task. Response-locked potentials were computed for errors of commission and for correct-hits. Scores for reality distortion syndrome, psychomotor poverty syndrome and disorganization syndrome were determined for each schizophrenic participant using the Signs and Symptoms of Psychotic Illness (SSPI) scale. RESULTS: ERN produced during error trials and CRN produced during correct trials were significantly larger in the control participant group than in the schizophrenic participant group. In the schizophrenic patients, ERN amplitude was negatively correlated with psychomotor poverty syndrome score and CRN amplitude was negatively correlated with disorganization syndrome score. CONCLUSIONS: Decreased ERN and CRN in the schizophrenic participant group suggests abnormal internal behavior monitoring in schizophrenic patients. Patients with high disorganization symptoms may employ an abnormal strategy for comparing actual response outcome with desired response outcome, while patients with psychomotor poverty may be less emotionally responsive to errors.

Adolescent↗

PubMed2002

PET study of the effects of valproate on dopamine D(2) receptors in neuroleptic- and mood-stabilizer-naive patients with nonpsychotic mania.

OBJECTIVE: A previous study reported a higher than normal density of dopamine D(2) receptors in psychotic mania but not in nonpsychotic mania. The purpose of this study was to further examine D(2) receptor density in a larger sample of nonpsychotic manic patients by using positron emission tomography (PET) and [(11)C]raclopride. METHOD: Thirteen neuroleptic- and mood- stabilizer-naive patients with DSM-IV mania without psychotic features and 14 healthy comparison subjects underwent [(11)C]raclopride PET scans. Of the 13 patients, 10 were treated with divalproex sodium monotherapy. PET scans were repeated 2-6 weeks after commencement of divalproex sodium. D(2) receptor binding potential was calculated by using a ratio method with the cerebellum as the reference region. RESULTS: The [(11)C]raclopride D(2) binding potential was not significantly different in manic patients than in the comparison subjects in the striatum. Treatment with divalproex sodium had no significant effect on the [(11)C]raclopride D(2) binding potential in manic patients. There was no correlation between the D(2) binding potential and manic symptoms before or after treatment. CONCLUSIONS: These results suggest that D(2) receptor density is not altered in nonpsychotic mania and that divalproex sodium treatment does not affect D(2) receptor availability.

Adolescent↗

PubMed2002

PET study of [(18)F]6-fluoro-L-dopa uptake in neuroleptic- and mood-stabilizer-naive first-episode nonpsychotic mania: effects of treatment with divalproex sodium.

OBJECTIVE: Although dopaminergic hyperactivity has been implicated in mania, the precise location in the brain of the abnormality is unclear. This study assessed presynaptic dopamine function in neuroleptic- and mood-stabilizer-naive nonpsychotic first-episode manic patients before and after treatment with divalproex sodium by measuring [(18)F]6-fluoro-L-dopa ([(18)F]DOPA) uptake in the striatum with positron emission tomography (PET). METHOD: Thirteen patients with DSM-IV bipolar I disorder, manic episode, and 13 healthy comparison subjects underwent [(18)F]DOPA PET scans. Ten of the 13 patients had repeat PET scans 2-6 weeks after beginning treatment with divalproex sodium monotherapy. [(18)F]DOPA uptake rate constants (K(i) values) in the striatum were calculated by using graphical analysis with activity from the occipital cortex as the input function. RESULTS: No significant differences in [(18)F]DOPA uptake rate constants in the striatum were found between the manic patients and the comparison subjects. After treatment with divalproex sodium, [(18)F]DOPA rate constants were significantly reduced in the patients and were lower in the patients than in the comparison subjects. CONCLUSIONS: Although presynaptic dopamine function as reflected by [(18)F]DOPA uptake is not altered in mania, presynaptic dopamine function in manic patients was lower after treatment with divalproex sodium.

Adult↗

PubMed2002

Signs and Symptoms of Psychotic Illness (SSPI): a rating scale.

BACKGROUND: In the rating scales commonly used for assessing response to antipsychotic treatment, individual items embrace symptoms that apparently arise from distinguishable pathophysiological processes and might be expected to respond differently to treatment. AIMS: To test the reliability, sensitivity to change and factor structure of a new scale for the assessment of the Signs and Symptoms of Psychotic Illness (the SSPI). METHOD: Interrater reliability was evaluated by determining the intraclass correlation for the ratings of 63 patients. Sensitivity to change was assessed in a longitudinal study of 33 patients. Factor structure was determined from scores for 155 patients. RESULTS: The intraclass correlation was satisfactory for all individual items and excellent for the total score. Scores were sensitive to change. A change in Clinical Global Impression of one unit corresponded to an SSPI total score change of 31%. Factor analysis revealed five clusters of symptoms. CONCLUSIONS: The SSPI provides a sensitive and reliable measure of the five major clusters of symptoms that occur commonly in psychotic illness.

Acute Disease↗

PubMed2002

Thought and Language Index: an instrument for assessing thought and language in schizophrenia.

BACKGROUND: Subtle formal thought disorders are difficult to quantify. Their relationship to florid thought disorder is unknown. AIMS: To assess the interrater reliability, sensitivity and factor structure of a new assessment instrument, the Thought and Language Index (TLI), and to determine if minor aberrations detectable in the speech of healthy individuals are related to the more severe formal thought disorders characteristic of schizophrenia. METHOD: Interrater reliability was evaluated by determining the intraclass correlation for the ratings by five assessors. Factor analysis of the TLI scores of 87 patients was performed, and TLI scores in matched patients and controls were compared. RESULTS: The intraclass correlation was good for individual TLI items, and excellent for sub-scale scores. Factor analysis identified three groups of approximately orthogonal disorders. Mild speech aberrations were observed in healthy participants and in patients with schizophrenia. The prevalence of mild aberrations was correlated with the prevalence of definite formal thought disorders. CONCLUSIONS: The TLI is reliable and capable of detecting subtle disorders. Some mild aberrations occurring in the speech of healthy individuals appear to be attenuated forms of the florid disorders characteristic of schizophrenia.

Adult↗

PubMed2002

Reading anomalous sentences: an event-related fMRI study of semantic processing.

We report a random-effects analysis of an event-related fMRI study (n = 28) of cerebral activity during the reading of sentences that ended with a word that was either congruent or incongruent with the previous sentence context. Event-related potential studies have shown that this task elicits a late negativity peaking around 400 ms poststimulus (N400) that is larger for incongruent than for congruent sentence endings. A direct comparison of the activation for incongruent words versus that for congruent words revealed significantly greater activation for incongruent words than congruent words in bilateral inferior frontal and inferio-medial temporal cortex, left lateral frontal cortex, left posterior fusiform gyrus, bilateral motor cortex, and supplementary motor area. These results are consistent with data from intracranial electrical recording studies of the N400 electrical potential. The results are discussed as they relate to the localization of the cerebral sites underlying semantic processing in general and the localization of the scalp recorded N400 event-related potential in particular.

Adult↗