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P J McKenna

Publications and source records attributed to P J McKenna.

At least 19 recordsLinked to original sources
PubMed2006

Psychiatric presentation of voltage-gated potassium channel antibody-associated encephalopathy. Case report.

Voltage-gated potassium channel antibody encephalopathy, a rare cause of limbic encephalopathy, typically presents with memory impairment and seizures. Psychiatric symptoms have not been emphasised in the literature. Here we describe a 58-year-old man who presented with panic attacks and psychogenic non-epileptic seizures and, later on, developed delusions and hallucinations and then confusion. He was found to have antibodies to voltage-gated potassium channels. Treatment with immuno-modulatory therapy resulted in almost complete recovery.

Antibodies↗
PubMed2006

Psychological effects of ketamine in healthy volunteers. Phenomenological study.

BACKGROUND: The psychosis-inducing effect of ketamine is important evidence supporting the glutamate hypothesis of schizophrenia. However, the symptoms the drug produces have not been described systematically. AIM: To examine the effects of ketamine in healthy people using a structured psychiatric interview. METHOD: Ketamine (200 ng/ml) or placebo was administered by continuous infusion to 15 healthy volunteers. Symptoms were rated using the Present State Examination, the Thought, Language and Communication Scale and the Scale for Assessment of Negative Symptoms. RESULTS: Ketamine induced a range of perceptual distortions, but not hallucinations. Referential ideas were seen in nearly half the sample. There were only mild and infrequent ratings on the thought disorder scale. Affective flattening and alogia were seen in some volunteers. CONCLUSIONS: Ketamine does not reproduce the full picture of schizophrenia. The main point of similarity concerns referential thinking. Phenomena resembling negative symptoms are also seen, but the distinction of these from the drug's sedative effects requires further elucidation.

Adult↗
PubMed2005

Formal thought disorder in schizophrenia: an executive or a semantic deficit?

BACKGROUND: It has been hypothesized that the schizophrenic symptom of formal thought disorder is linked to both executive and semantic dysfunction. METHOD: Intellectually preserved schizophrenic patients with (n = 15) and without (n = 16) formal thought disorder, plus matched normal controls (n = 17) were administered four executive and four semantic tests. Tests of verbal fluency and comprehension of grammar were also given. RESULTS: The patients with formal thought disorder were significantly impaired on all four executive tests compared to the patients without the symptom. They were only impaired compared to non-thought-disordered patients on 1 of 4 semantic tests, which probed semantic associations between concepts. Naming performance did not distinguish the two groups, nor did a previously used measure of semantic fluency controlling for phonological fluency. CONCLUSIONS: The results provide support for a dysexecutive hypothesis of formal thought disorder in schizophrenia, and, in line with other studies, suggest that there may be a restricted 'higher-order' semantic deficit which spares naming.

Adult↗
PubMed2005

Diabetes associated with atypical antipsychotic treatment may be severe but reversible: case report.

OBJECTIVE: To draw attention to severe presentations of atypical neuroleptic related diabetes and to document that a marked degree of remission can take place after drug withdrawal. METHOD: We describe two patients who presented with diabetic ketoacidosis after treatment with quetiapine and risperidone, respectively. RESULTS: Both patients were negative for islet cell antibodies. They both required treatment with insulin, one in very high dosage, but their insulin requirements fell progressively after the atypical antipsychotic was withdrawn. After several months, neither patient required antidiabetic treatment. CONCLUSIONS: Atypical antipsychotic-induced diabetes does not always take a "type 2" presentation in which weight gain and insulin resistance are implicated. Sometimes the presentation is with diabetic ketoacidosis, requiring insulin treatment, which can nevertheless be reversible.

Adult↗
PubMed2004

Can disorganisation of semantic memory account for the abnormalities of thought in schizophrenia-a controlled experimental study.

BACKGROUND: Disorganisation of semantic memory could provide a cognitive explanation for the disturbances of thinking and reasoning in schizophrenia. In this study, we directly test this explanation by identifying patients with disorganised semantic categories and then examine how they use their knowledge about these same categories in an inductive reasoning task. METHOD: Experiment 1 utilised a semantic category-sorting task to identify patients with disorganisation of semantic memory. In Experiment 2, the patients with disorganised categories carried out a category-based inductive reasoning task. Accurate performance on this task requires access to well-organised semantic knowledge about the objects and categories used in Experiment 1. RESULTS: Patients with disorganised semantic categories in Experiment 1 did not demonstrate any difficulties or unusual responses when reasoning about the same categories in Experiment 2. CONCLUSION: Disorganisation of semantic memory may not be the primary cause of disturbed reasoning or thought in schizophrenia. Patients with schizophrenia tend to generate ad hoc categories, which are unsuited to the current context. Impaired performance on semantic memory tasks can arise from a misunderstanding of social context.

Adult↗
PubMed2004

Hypofrontality in schizophrenia: a meta-analysis of functional imaging studies.

OBJECTIVE: Hypofrontality is not a well-replicated finding in schizophrenia either at rest or under conditions of task activation. METHOD: Studies comparing whole brain and frontal blood flow/metabolism in schizophrenic patients and normal controls were pooled. Voxel-based studies were also combined to examine the pattern of prefrontal activation in schizophrenia. RESULTS: Whole brain flow/metabolism was reduced in schizophrenia to only a small extent. Resting and activation frontal flow/metabolism were both reduced with a medium effect size. Duration of illness significantly moderated resting hypofrontality, but the moderating effects of neuroleptic treatment were consistent with an influence on global flow/metabolism only. Pooling of voxel-based studies did not suggest an abnormal pattern of activation in schizophrenia. CONCLUSION: Meta-analysis supports resting hypofrontality in schizophrenia. Task-activated hypofrontality is also supported, but there is little from voxel-based studies to suggest that this is associated with an altered pattern of regional functional architecture.

Frontal Lobe↗
PubMed2004

Spontaneous improvement in severe, chronic schizophrenia and its neuropsychological correlates.

Cognitive impairment is well established in schizophrenia but its relationship to the course of the illness remains incompletely understood. Here we document two patients with schizophrenia who underwent neuropsychological testing while chronically unwell, and this was repeated after improvement took place. Both patients showed significant recovery of general intellectual function, accompanied by improvements in some but not all areas of neuropsychological function: executive function remained particularly impaired.

Adult↗
PubMed2003

GABAergic inhibitory mechanisms for repetition-adaptivity in large-scale brain systems.

Molecular mechanisms for systems level adaptivity of brain activation are largely unknown but a key role for active inhibition by gamma-aminobutyric acid (GABA) is plausible. We used functional magnetic resonance imaging to contrast the modulatory effects on brain adaptivity to task repetition and task difficulty of two GABAergic drugs, lorazepam and flumazenil. In a working memory paradigm, occipitotemporal regions clearly demonstrated attenuation of activation as a function of within-session task repetition or practice in data acquired following placebo, but this spatiotemporal pattern of repetition adaptivity was abolished by both lorazepam and flumazenil. However, in other brain systems flumazenil enhanced repetition adaptivity compared to placebo: in frontal cortex, flumzenil induced attenuation of signal related to task repetition and in hippocampus it exaggerated normal enhancement of signal with repetition. In contrast, there were no significant effects of either flumazenil or lorazepam on areas of frontal cortex which normally demonstrated significant neurocognitive load response or adaptivity to task difficulty. We argue that repetition adaptivity of large-scale brain systems is regulated by GABAergic inhibitory mechanisms and that expression of repetition adaptivity in a given brain system may show an "inverted-U" form of relationship with pharmacologically manipulable levels of GABAergic inhibitory tone.

Adult↗
PubMed2003

Brain morphological abnormality in schizophrenia is independent of country of origin.

OBJECTIVE: The disorder schizophrenia has a worldwide prevalence of 1% and is generally associated with lateral cerebral ventricular enlargement. Whether there is a relationship between these two findings is unclear but has aetiological relevance. METHOD: Consecutively admitted Chinese patients (n = 19) with first episode of schizophrenia and healthy community volunteers (n = 29) underwent magnetic resonance imaging brain scan. The groups were balanced for age, sex, best social class and handedness. These patients were similar on clinical and socio-demographic indices to those who declined participation (n = 15). Semi-automated volumetric analysis of whole brain volume, cortical grey matter, cerebrospinal fluid, sulci and lateral ventricles was performed. RESULTS: Chinese patients in their first episode of schizophrenia have significant enlargement of lateral ventricles. CONCLUSION: Brain morphological abnormality in schizophrenia is present regardless of the country of origin. The importance of genes in driving normal brain development and stable prevalence suggests that aetiology may favour genes over environment.

Adult↗
PubMed2003

The association between negative and dysexecutive syndromes in schizophrenia: a cross-cultural study.

This paper examined the relationship between the 'negative syndrome' (NS) and the neuropsychological 'dysexecutive syndrome' (DES) in schizophrenia. The study also examined whether any relationship that exists between the NS and the DES holds equally for British and Japanese subjects. We compared 26 Japanese with 17 British schizophrenic patients, divided into 'mild' and 'severe' NS groups, on the basis of performance on neuropsychological tests, including the 'Behavioural Assessment of Dysexecutive Syndrome' (BADS). We found that patients with severe NS showed more everyday executive deficits than those with mild NS. The severity of NS was correlated with executive competence. The association between NS and the BADS performance was closer than that between NS and other conventional executive measures. These findings were not influenced by cultural differences between Japanese and British subjects, and, hence, suggested the existence of culture-neutral neurobehavioural processes.

Adult↗
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

Narcolepsy and psychopathology: is there an association?

BACKGROUND: It is widely believed that patients with narcolepsy show high rates of associated psychiatric disturbance, especially schizophrenia and depression. However, surveys have produced conflicting findings and have not addressed the potential confounding effects of stimulant drug treatment. METHOD: Forty-five patients with narcolepsy attending a sleep disorder clinic and 50 matched normal controls underwent structured psychiatric interview. Using a 'lifetime' approach, psychiatric symptoms and diagnoses were established for both groups. RESULTS: Four of the narcolepsy patients but none of the controls had experienced psychotic symptoms. All four patients were taking amphetamines, and the symptoms resolved when the dose was lowered or treatment was changed to modafinil. The lifetime frequency of various depressive syndromes did not differ significantly between the groups. CONCLUSIONS: Contrary to previous claims this study found little to suggest that narcolepsy is associated with schizophrenia. Nor, despite its serious social and occupational consequences, does narcolepsy appear to be associated with an increased frequency of diagnosable depressive disorders.

Journal Article↗
PubMed2002

Is there a schizophasia? A study applying the single case approach to formal thought disorder in schizophrenia.

It has been suggested that formal thought disorder, the incoherent speech of schizophrenia, may involve a language disturbance among other abnormalities, or even be a form of dysphasia. Six patients with and seven without formal thought disorder were evaluated on an aphasia test battery. Spontaneous speech was also analysed using Brief Syntactic Analysis. Poor performance on the aphasia test battery was found to be associated with general intellectual impairment but not with formal thought disorder. Naming was preserved in both groups. Patients with formal thought disorder, but not those without, produced semantic errors in their spontaneous speech, and these were unrelated to general intellectual status. The disorder of language in formal thought disorder thus appears to be one of expressive semantic abnormality, which, however, spares naming. Further analysis of two intellectually preserved patients suggested that formal thought disorder may be associated with an additional difficulty in constructing an appropriate model for generating one's own speech.

Adult↗
PubMed2001

Language in schizophrenia and its relationship to formal thought disorder.

BACKGROUND: Although poor language test performance has been documented in schizophrenia, its relationship to formal thought disorder remains unclear. METHOD: Forty schizophrenic patients were administered eight language tests and, under blind conditions, rated for formal thought disorder. Measures of general intellectual function were also obtained. RESULTS: Performance on all language tests was significantly correlated with the general intellectual measures. Three language test scores also showed significant correlations with formal thought disorder scores. Multiple regression and analysis of intellectually preserved patients suggested particular associations of formal thought disorder with semantic comprehension and picture description. CONCLUSIONS: General intellectual impairment is an important determinant of poor language test performance in schizophrenia, but presence of formal thought disorder may also contribute. A higher-order semantic deficit may be particularly relevant to both linguistic impairment and formal thought disorder.

Adult↗
PubMed2001

Plasma P-selectin is elevated in the first trimester in women who subsequently develop pre-eclampsia.

OBJECTIVE: To report plasma concentrations of the adhesion cell molecule P-selectin during pregnancy to determine the effect of subsequent development of hypertension and pre-eclampsia. DESIGN: A longitudinal study. METHODS: A longitudinal study involving 70 women followed up from early pregnancy; 20 who subsequently developed pre-eclampsia were compared with 24 who developed gestational hypertension and 26 normotensive women with normal obstetric outcome. The determination of citrate plasma soluble P-selectin levels throughout pregnancy was performed using a commercial quantitative sandwich immunoassay kit. The temporal course of plasma P-selectin in the three groups of subjects was analysed. RESULTS: There was no significant difference in mean plasma P-selectin concentration between normotensive and gestational hypertensive subjects at any stage of pregnancy. Using a cutoff level of 60 ng/mL, P-selectin concentration at 10-14 weeks had a negative predictive value for pre-eclampsia of almost 99%. Mean plasma P-selectin concentrations were significantly elevated by 10-14 weeks in women who later developed pre-eclampsia (P < 0.001). CONCLUSIONS: Our data support an inflammatory model for pre-eclampsia whereby endothelial cell activation may be secondary to a primary inflammatory response. Plasma P-selectin has significant potential as a first trimester clinical marker of pre-eclampsia.

Adult↗
PubMed2001

Dementia as a complication of schizophrenia.

OBJECTIVES: Cognitive impairment is known to occur in schizophrenia, and may be marked in institutionalised patients. The aim of this study was to determine whether it ever warrants an additional diagnosis of dementia. METHODS: A population of chronic schizophrenic patients who were aged 65 or younger and showed no organic risk factors for dementia were screened for presence of disorientation. Any showing this underwent neuropsychological testing, physical investigations, and structural and functional neuroimaging. Information about day to day cognitive function was also obtained from carers. RESULTS: Eight patients aged 28 to 64 were identified who showed disorientation; in all cases this was accompanied by general intellectual impairment and objective evidence of a dementia syndrome. The patients' schizophrenic symptoms were unexceptional and did not seem sufficient to account for their cognitive impairment. Neuropsychological testing disclosed relative sparing of visual and visuospatial function and language syntax, but pervasive deficits in memory and executive function. Brain CT demonstrated only minor abnormalities but most of the patients showed frontal or temporal hypoperfusion on SPECT. CONCLUSIONS: Dementia in schizophrenia seems to be a real entity with a neuropsychological signature similar to that of frontotemporal dementia. Functional but not structural imaging abnormalities may also be characteristic.

Adult↗
PubMed2000

Gene expression of metabotropic glutamate receptor 5 and excitatory amino acid transporter 2 in the schizophrenic hippocampus.

A disturbance in glutamatergic transmission has been suggested to contribute to the pathophysiology of schizophrenia and recent studies on ionotropic glutamate receptors are consistent with altered glutamatergic function in the hippocampus of schizophrenics. In order to investigate this hypothesis further, the expression of two 'glutamatergic' markers, the mRNAs of metabotropic glutamate receptor 5 (mGluR5) and human excitatory amino acid transporter (EAAT2) were compared in the hippocampus of control subjects and schizophrenics. We examined the regional/cellular mRNA expression of mGluR5 and EAAT2 in postmortem hippocampal sections from schizophrenics and control subjects, using in situ hybridization. Regions of interests were dentate gyrus, cornu ammonis 4, 3, 1 and parahippocampal gyrus. The regional/cellular mGluR5 mRNA content was not different between the two groups. The cellular EAAT2 mRNA content was significantly decreased in schizophrenic parahippocampal gyrus, but not in other hippocampal regions. Furthermore, only in the parahippocampal gyrus, schizophrenics had a significantly increased mGluR5/EAAT2 ratio at both the regional and cellular mRNA level. The results suggest that a disturbance of glutamatergic neurotransmission in schizophrenia was not apparent using these indices in the hippocampus, but 'hypo-glutamatergic' neurotransmission may be present in the schizophrenic parahippocampal gyrus.

Actins↗