Biomedical subjects

E M Joyce

Publications and source records attributed to E M Joyce.

At least 19 recordsLinked to original sources

PubMed2002

Decision making deficits in patients with first-episode and chronic schizophrenia.

A considerable body of evidence suggests that the dorsolateral prefrontal cortex is dysfunctional in schizophrenia. However, relatively few studies have explored the involvement of other areas of the frontal cortex. Research suggests that the orbitofrontal cortex (OFC) plays an important role in decision making processes. We assessed the decision making cognition of first-episode and chronic schizophrenic patients with a novel task sensitive to orbitofrontal dysfunction. Both first-episode and chronic patients with schizophrenia took longer than matched controls to make decisions, and both groups were also impaired on a measure of risk adjustment. The impairment in these measures was more severe in the chronic patients than in the first-episode patients, and only the chronic patients made significantly fewer optimal decisions than controls. These results contribute to increasing evidence of orbitofrontal dysfunction in schizophrenia, and suggest that disease progression or the effects of long term antipsychotic medication may influence performance on this task.

Analysis of Variance↗

PubMed2002

Saccadic distractibility in first-episode schizophrenia.

In the antisaccade paradigm, subjects are instructed to fixate a central point, and then move their eyes towards a position in space in the opposite direction but equidistant to a peripheral, sudden onset target. Antisaccade errors occur when subjects are "distracted" by the target and make a saccade towards it. These errors are more common in patients with schizophrenia but the underlying cause remains unclear. To determine whether antisaccade errors simply reflect a general inability to maintain fixation or are the consequence of a more specific deficit in the strategic control of internally generated actions, patients with first-episode schizophrenia and healthy controls performed three saccadic paradigms which shared the core feature of requiring a prepotent saccade to be suppressed, but varied in their concurrent cognitive demands. We found that both groups showed an increase in errors as the cognitive demands increased across task. However, this increase was significantly steeper in the schizophrenic patients than in the controls. We also found that schizophrenic patients were as able as controls to inhibit prepotent saccades towards a target in a paradigm with no other cognitive demands. Possible explanations of these results include reduced working memory resources and impaired motor preparation in schizophrenia.

Adult↗

PubMed2001

Synthesis of polybrominated diphenyl ethers and their capacity to induce CYP1A by the Ah receptor mediated pathway.

Polybrominated diphenyl ethers (PBDEs) have become widely distributed as environmental contaminants due to their use as flame retardants. Their structural similarity to other halogenated aromatic pollutants has led to speculation that they might share toxicological properties such as hepatic enzyme induction. In this work we synthesized a number of PBDE congeners, studied their affinity for rat hepatic Ah receptor through competitive binding assays, and determined their ability to induce hepatic cytochrome P-450 enzymes by means of EROD (ethoxyresorufin-O-deethylase) assays in human, rat, chick, and rainbow trout cells. Both pure PBDE congeners and commercial PBDE mixtures had Ah receptor binding affinities 10(-2)-10(-5) times that of 2,3,7,8-tetrachlorodibenzo-p-dioxin. In contrast with polychlorinated biphenyls, Ah receptor binding affinities of PBDEs could not be related to the planarity of the molecule, possibly because the large size of the bromine atoms expands the Ah receptor's binding site. EROD activities of the PBDE congeners followed a similar rank order in all cells. Some congeners, notably PBDE 85, did not follow the usual trend in which strength of Ah receptor binding affinity paralleled P-450 induction potency. Use of the gel retardation assay with a synthetic oligonucleotide indicated that in these cases the liganded Ah receptor failed to bind to the DNA recognition sequence.

Animals↗

PubMed2001

A serial longitudinal quantitative MRI study of cerebral changes in first-episode schizophrenia using image segmentation and subvoxel registration.

Lateral ventricular enlargement is the most consistently replicated brain abnormality found in schizophrenia. This article reports a first episode, longitudinal study of ventricular volume using high-resolution serial magnetic resonance imaging (MRI) and recently developed techniques for image registration and quantitation. Baseline and follow-up (on average 8 months later) MRI scans were carried out on 24 patients and 12 controls. Accurate subvoxel registration was performed and subtraction images were produced to reveal areas of regional brain change. Whereas there were no differences between patients and controls with respect to the mean change in ventricular volume, the patients were much more variable in this respect and showed larger increases and decreases. The percentage increase in ventricular size was greater than one standard deviation of control values for 14 patients and the percentage decrease exceeded one standard deviation in eight patients. Although the finding of progressive ventricular enlargement in a proportion of patients supports other studies indicating an ongoing neuropathological process in the early stages of schizophrenia, the reduction of ventricular size in the remaining patients is more difficult to explain. It is suggested that this may reflect improvement in nutrition and hydration following treatment.

Adult↗

PubMed2001

Short and long term effects of antipsychotic medication on smooth pursuit eye tracking in schizophrenia.

RATIONALE: Smooth pursuit abnormalities have been observed in antipsychotic naive first-episode patients, suggesting that they are intrinsic to the illness. However, it is not clear whether these abnormalities are as severe as those observed in more chronic patients. In addition, although research suggests that there are no short-term effects of conventional antipsychotic medication, the effects of long-term antipsychotic medication on smooth pursuit eye movements are relatively unknown. OBJECTIVES: To determine the short and long term effects of antipsychotic medication on the smooth pursuit performance of first-episode and chronic patients with schizophrenia. METHODS: We compared the smooth pursuit performance of antipsychotic-treated and untreated first-episode and chronic schizophrenic patients with healthy controls using a comprehensive range of performance measures. This included velocity gain, the number, type and size of intrusive and corrective saccades, and the average time between the change in direction of the target and the change in direction of the eye movement, a measure of subjects' ability to predict target movement. RESULTS: Chronic schizophrenic patients had significantly reduced velocity gain, took longer to respond to the change in target direction and made more catch-up saccades than both first-episode schizophrenic patients and controls. First-episode patients were impaired relative to controls only on the measure of velocity gain. There were no differences between antipsychotic-naive and treated first-episode patients. Antipsychotic-free chronic patients were significantly less impaired on velocity gain than matched continuously treated chronic patients. These results were not influenced by group differences in age and symptom severity. CONCLUSIONS: These results show that: 1) the main index of smooth pursuit, velocity gain, is impaired early in the course of schizophrenia; 2) whereas velocity gain is unaffected by short-term (weeks) medication, it is worsened by chronic (years) treatment; 3) other indices of smooth pursuit, catch-up saccades and ability to predict target movement, are adversely influenced by illness chronicity rather than medication.

Adult↗

PubMed2001

Saccadic hypometria in drug-naive and drug-treated schizophrenic patients: a working memory deficit?

In certain conditions patients with schizophrenia make markedly smaller (hypometric) saccades than controls. This hypometria has been thought to reflect dopaminergic blockade as a result of antipsychotic medication. We tested this hypothesis by comparing the performance of an antipsychotic-naïve group and an antipsychotic-treated group of first-episode schizophrenic patients on a predictive saccade paradigm. We explored the possibility that hypometria reflects a spatial working memory deficit by correlating performance on neuropsychological tests of mnemonic function with saccadic accuracy. Both the drug-naïve and treated schizophrenic patients made hypometric saccades when compared with a group of matched controls. Primary saccade amplitude also correlated significantly with performance on some of the neuropsychological tests. These results are discussed in terms of the roles of cortical dopamine and working memory deficits in schizophrenic patients.

Adult↗

PubMed2000

Smooth pursuit eye tracking over a structured background in first-episode schizophrenic patients.

Whilst most laboratory smooth pursuit tasks are performed in the dark, in everyday life pursuit commonly occurs over a structured background. This background provides a powerful stimulus to the optokinetic reflex (OKR), inducing a background "drag" on pursuit eye movements. An inability to inhibit the influence of the OKR may be a contributing factor to the dysfunctional pursuit performance observed in many schizophrenic patients. Smooth pursuit performance was measured in 23 first-episode schizophrenic patients and 23 healthy controls matched for age and estimated IQ, both in the dark and over a structured background (a random checkerboard of black and white squares). Velocity gain was measured, as well as the number and size of corrective saccades (catch-up saccades) and intrusive saccades (anticipatory saccades and square wave jerks). Overall, schizophrenic patients had lower velocity gain and made more catch-up saccades than controls. The effect of the background was to lower velocity gain and increase the number of catch-up saccades to the same extent in schizophrenic patients and controls. There were no significant interactions between group and background effect. These results suggest that, although their overall level of performance was worse, the schizophrenic patients were as able as controls to inhibit the effect of the OKR. Since lesion studies show that inhibition of the OKR requires intact inferior parietal regions in man (Lawden et al., 1995), one hypothesis is that the parietal component of smooth pursuit may be intact in schizophrenia.

Adult↗

PubMed2000

West London first-episode study of schizophrenia. Clinical correlates of duration of untreated psychosis.

BACKGROUND: Studies in schizophrenia suggest that a longer initial period of untreated illness is associated with a poorer clinical outcome. AIMS: To determine whether, in first-episode schizophrenia, a longer duration of untreated psychosis (DUP) or of untreated illness (DUI) (DUP plus any prodrome) is associated with clinical variables that could mediate a poor prognosis. METHOD: Clinical, social, neuropsychological and oculomotor function data on 53 patients with first-episode schizophrenia were related to the DUP and DUI. RESULTS: Comparing short and long DUP groups split around the median showed no statistically significant differences (except age); patients in the latter group tended to perform worse on an executive attentional set-shifting task, and were more likely to be unemployed, and living alone or homeless. CONCLUSIONS: There was little evidence of any association between either DUP or DUI and progressive deterioration in the schizophrenic illness or the development of resistance to initial drug treatment. Social variables that augur a poor prognosis may be associated with delayed presentation of schizophrenia to psychiatric services.

Adult↗

PubMed1999

Ability of polycyclic aromatic hydrocarbons to induce 7-ethoxyresorufin-o-deethylase activity in a trout liver cell line.

Along with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 24 unsubstituted polycyclic aromatic hydrocarbons (PAHs) were evaluated for their ability to induce 7-ethoxyresorufin-o-deethylase (EROD) activity in the rainbow trout liver cell line RTL-W1. When the duration and cell density of exposure were increased, the EC(50) for EROD induction was relatively constant for TCDD, but increased for PAHs. Regardless of exposure conditions, EROD activity was not induced by 9 PAHs: naphthalene, phenanthrene, anthracene, pyrene, perylene, acenaphthylene, acenaphthene, fluorene, and fluoranthene. Two PAHs, benzo[g,h,i]perylene and coronene, induced EROD activity inconsistently. The remaining 13 PAHs consistently induced EROD activity. The EC(50)s for induction exhibited approximately a 110-fold range. The order of potency, from most to least potent, was benzo[k]fluoranthene, dibenzo[a,i]pyrene, dibenzo [a,h]anthracene, benzo[a]pyrene, indeno[1,2,3-cd]pyrene, benzo [b]fluoranthene, pentacene, benzo[b]anthracene, benzo[b] fluorene, chrysene, benzo[a]anthracene, benzo[e]pyrene, and triphenylene. When the induction potency was expressed relative to TCDD, the toxic equivalency factors (TEFs) ranged from 0.001 to 0.000 01. When expressed relative to benzo[a]pyrene, the TEFs ranged from 3.44 to 0. 03.

Animals↗

PubMed1999

Development and characterization of a cell line from Pacific herring, Clupea harengus pallasi, sensitive to both naphthalene cytotoxicity and infection by viral hemorrhagic septicemia virus.

A cell line, PHL, has been successfully established from newly hatched herring larvae. The cells are maintained in growth medium consisting of Leibovitz's L-15 supplemented with 15% fetal bovine serum (FBS), and have been cryopreserved and maintain viability after thawing. These cells retain a diploid karotype after 65 population doublings. PHL are susceptible to infection by the North American strain of viral hemorrhagic septicemia (VHS) virus, and are sensitive to the cytotoxic effects of naphthalene, a common environmental contaminant. Naphthalene is a component of crude and refined oil, and may be found in the marine environment following acute events such as oil spills. In addition, chronic sources of naphthalene contamination include offshore drilling and petroleum contamination from areas such as docks and marinas that have creosote-treated docks and pilings and also receive constant small inputs of petroleum products. This cell line should be useful for investigations of the toxicity of naphthalene and other petroleum components to juvenile herring. In addition, studies of the VHS virus will be facilitated by the availability of a susceptible cell line from an alternative species.

Animals↗

PubMed1999

Conditions under which lorazepam can facilitate retrieval.

Memory is composed of three stages: acquisition, consolidation, and retrieval. By impairing acquisition processes, benzodiazepines cause anterograde amnesia while leaving intact information learned before the drug was taken. In some circumstances, retrieval of this information is even improved by benzodiazepines. It has been hypothesized that this phenomenon is not a true facilitation of retrieval processes, but is the result of reduced interference from items presented after drug administration and is thus a secondary consequence of drug-induced amnesia. Experiment 1 investigated the effect of 0.5, 1, and 2.5 mg of lorazepam on explicit episodic memory in healthy young volunteers. The 1-mg dose was found to significantly improve recall of items presented before drug administration without causing amnesia for items presented after drug administration, thus excluding an interference explanation. Experiment 2 investigated the conditions necessary to obtain facilitated retrieval with 1 mg of lorazepam. The results showed that facilitation was found only when two lists of semantically related material were presented, but that both of the lists could be presented before drug administration, thus excluding an effect of lorazepam on consolidation. Facilitation could be demonstrated in both direct (free recall) and indirect (backwards reading) retrieval tasks and when all of the material was presented after lorazepam administration. This improved retrieval could therefore be of clinical relevance, but any benefits would be reduced at higher doses that at the same time impair acquisition of new information. However, because 1 mg of lorazepam is an effective anxiolytic dose, these results suggest that it is possible to combine effective anxiety reduction with some benefits to memory.

Adolescent↗

PubMed1999

Spontaneous dyskinesia in first episode schizophrenia.

In the west London prospective study of first episode schizophrenia, the prevalence and nature of abnormal involuntary movements were examined in 27 patients who had never received antipsychotic drugs and 36 who had been treated with such medication. Motor disturbance was assessed with rating scales designed to cover the full range of spontaneous and drug induced movement disorder. Only one person in the drug naive group showed evidence ofparkinsonism, a finding which contrasts with recent reports suggesting that spontaneous extrapyramidal signs may not be uncommon in such patients. However, according to ratings on the modified Rogers scale, 11% of the drug naive group exhibited orofacial dyskinesia, 4% trunk and limb dyskinesia, 7% postural abnormalities, and 4% increased muscle tone. The respective figures in the closely matched medicated group were not significantly different except for increased muscle tone, which was significantly more common (25%). The proportion of drug naive patients fulfilling criteria for tardive dyskinesia on the abnormal involuntary movements scale ranged from 4% to 11% depending on the criterion threshold score used. These findings are in accord with the notion that abnormal involuntary movements, particularly orofacial dyskinesia, represent a neuromotor component of schizophrenia.

Adolescent↗

PubMed1999

Heat shock-induced acquisition of thermotolerance at the levels of cell survival and translation in Xenopus A6 kidney epithelial cells.

In this study we have investigated the acquisition of thermotolerance in a Xenopus laevis kidney A6 epithelial cell line at both the level of cell survival and translation. In cell survival studies, A6 cells were incubated at temperatures ranging from 22 to 35 degrees degrees C for 2 h followed by a thermal challenge at 39 degrees degrees C for 2 h and a recovery period at 22 degrees C for 24 h. Optimal acquisition of thermotolerance occurred at 33 degrees degrees C. For example, exposure of A6 cells to 39 degrees degrees C for 2 h resulted in only 3.4% survival of the cells whereas prior exposure to 33 degrees C for 2 h enhanced the survival rate to 69%. This state of thermotolerance in A6 cells was detectable after 1 h at 33 degrees C and was maintained even after 18 h of incubation. Cycloheximide inhibited the acquisition of thermotolerance at 33 degrees C suggesting the requirement for ongoing protein synthesis. The optimal temperature for the acquisition of translational thermotolerance also occurred at 33 degrees C. Treatment of A6 cells at 39 degrees C for 2 h resulted in an inhibition of labeled amino acid incorporation into protein which recovered to approximately 14% of control after 19 h at 22 degrees C whereas cells treated at 33 degrees C for 2 h prior to the thermal challenge recovered to 58% of control levels. These translationally thermotolerant cells displayed relatively high levels of the heat shock proteins hsp30, hsp70, and hsp90 compared to pretreatment at 22, 28, 30, or 35 degrees C. These studies demonstrate that Xenopus A6 cells can acquire a state of thermotolerance and that it is correlated with the synthesis of heat shock proteins.

Animals↗

PubMed1998

Executive function in first-episode schizophrenia.

BACKGROUND: We tested the hypothesis that schizophrenia is primarily a frontostriatal disorder by examining executive function in first-episode patients. Previous studies have shown either equal decrements in many cognitive domains or specific deficits in memory. Such studies have grouped test results or have used few executive measures, thus, possibly losing information. We, therefore, measured a range of executive ability with tests known to be sensitive to frontal lobe function. METHODS: Thirty first-episode schizophrenic patients and 30 normal volunteers, matched for age and NART IQ, were tested on computerized test of planning, spatial working memory and attentional set shifting from the Cambridge Automated Neuropsychological Test Battery. Computerized and traditional tests of memory were also administered for comparison. RESULTS: Patients were worse on all tests but the profile was non-uniform. A componential analysis indicated that the patients were characterized by a poor ability to think ahead and organize responses but an intact ability to switch attention and inhibit prepotent responses. Patients also demonstrated poor memory, especially for free recall of a story and associate learning of unrelated word pairs. CONCLUSIONS: In contradistinction to previous studies, schizophrenic patients do have profound executive impairments at the beginning of the illness. However, these concern planning and strategy use rather than attentional set shifting, which is generally unimpaired. Previous findings in more chronic patients, of severe attentional set shifting impairment, suggest that executive cognitive deficits are progressive during the course of schizophrenia. The finding of severe mnemonic impairment at first episode suggests that cognitive deficits are not restricted to one cognitive domain.

Adolescent↗

PubMed1998

Smooth pursuit and saccadic abnormalities in first-episode schizophrenia.

BACKGROUND: Previous studies of oculomotor dysfunction in schizophrenia have tended to concentrate on abnormalities of smooth pursuit eye tracking in chronic medicated patients. We report the results of a study of smooth pursuit, reflexive and antisaccade performance in drug naive and antipsychotic treated first-episode schizophrenic patients. METHODS: Smooth pursuit and saccadic eye movements were recorded in 36 first-episode schizophrenic patients and 36 controls matched for age and estimated IQ. The schizophrenic patients were divided into drug-naive (N = 17) and antipsychotic treated groups (N = 19). RESULTS: Smooth pursuit velocity gain was significantly lower than controls only in the drug-naive patients. The treated patients did not differ significantly from either the controls or the untreated group. In an antisaccade paradigm both treated and drug-naive schizophrenic patients demonstrated an increased number of errors, but only drug-naive patients also demonstrated an increased latency in initiating correct antisaccades. CONCLUSIONS: These impairments are unlikely to be due to a generalized deficit in oculomotor function in the schizophrenic groups, as there were no differences between the groups in saccadic metrics on a reflexive saccade task. The results show that both smooth pursuit and saccadic abnormalities are present at the onset of schizophrenia and are integral to the disorder.

Adolescent↗

PubMed1996

Verbal fluency in schizophrenia: relationship with executive function, semantic memory and clinical alogia.

To examine whether poor verbal fluency in schizophrenia represents a degraded semantic store or inefficient access to a normal semantic store, 25 normal volunteers and 50 DSM-III-R schizophrenic patients, matched for age, sex and IQ, were recruited. Although schizophrenic patients were impaired on both letter and category fluency, they showed a normal pattern of output in that category was superior to letter fluency, and an improvement in category fluency when a cueing technique was employed (Randolph et al. 1993). These results resemble those found in disorders of frontostriatal systems (Parkinson's and Huntington's disease) and suggest that poor verbal fluency in schizophrenia is because of inefficient access to semantic store. A measure of improvement with cueing was directly related to performance on the Stroop executive task. Of all symptom measures derived from SANS and Manchester Scales, only alogia was related to verbal fluency in that superior improvement correlated inversely with the degree of alogia. It is suggested that both alogia and poor verbal fluency are mediated by the same underlying cognitive abnormality that reflects frontostriatal dysfunction.

Adult↗

PubMed1994

Decreased cingulate and precuneate glucose utilization in alcoholic Korsakoff's syndrome.

Localized cerebral glucose utilization was determined for nine abstinent alcoholic men with Korsakoff's syndrome and 10 age-matched normal men who underwent positron emission tomography with [18F]2-fluoro-2-deoxyglucose (FDG). Patients with Korsakoff's syndrome showed relatively decreased glucose utilization in cingulate and precuneate areas. These decreases persisted even after correction for group differences in ventricular and sulcal cerebrospinal fluid measured on computed tomography. Electroencephalographic recordings at the time of FDG uptake showed no group differences, a finding that demonstrates that the metabolic differences could not be explained by differences in physiological arousal at the time of scanning. It is concluded that the decreased glucose utilization in the patients reflects a disruption of memory circuitry, the Papez circuit, caused by diencephalic lesions induced by thiamine deficiency.

Aged↗

PubMed1994

Aetiology of alcoholic brain damage: alcoholic neurotoxicity or thiamine malnutrition?

The clinical presentation of brain damaged alcoholics is heterogenous and includes minimal cognitive impairment, amnesia and dementia. Whichever neurobiological technique is used, eg neuropathology, structural and functional neuroimaging, the clinico-pathological evidence suggests that thiamine malnutrition, affecting the diencephalon, can account for all clinical forms. Alcohol neurotoxicity can cause neuronal damage in cerebral cortex and can contribute to cognitive impairment but there is little direct evidence to support the need for a distinct clinical category of alcoholic dementia. Most organic brain syndromes in alcoholics therefore can be considered as variants of the Wernicke-Korsakoff syndrome and rigorous attention should be paid to the nutritional status of all alcoholics.

Alcoholism↗