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G K Murray
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ABSTRACT: This article examines a model of how delusions may arise, not just in schizophrenia but also in a number of neurological and psychiatric conditions, through a combination of dysregulated dopamine release from ascending midbrain pathways and reasoning bias. Negative symptoms may also be related to dopamine dysregulation, with the precise mixture of positive and negative symptoms depending on the relative degree of dopamine dysregulation in particular mesocorticolimbic circuits. Evidence for this model is examined, and predictions arising from this model are described.
Psychological Medicine 01/2011; 41(1):7-13. · 6.16 Impact Factor
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F Cheng,
J B Kirkbride,
B R Lennox,
J Perez,
K Masson,
K Lawrence,
K Hill,
L Feeley,
M Painter, G K Murray,
O Gallagher,
E T Bullmore,
P B Jones
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ABSTRACT: Early Intervention in Psychosis Services (EIS) for young people in England experiencing first-episode psychosis (FEP) were commissioned in 2002, based on an expected incidence of 15 cases per 100 000 person-years, as reported by schizophrenia epidemiology in highly urban settings. Unconfirmed reports from EIS thereafter have suggested higher than anticipated rates. The aim of this study was to compare the observed with the expected incidence and delineate the clinical epidemiology of FEP using epidemiologically complete data from the CAMEO EIS, over a 6-year period in Cambridgeshire, for a mixed rural-urban population.
A population-based study of FEP (ICD-10, F10-39) in people aged 17-35 years referred between 2002 and 2007; the denominator was estimated from mid-year census statistics. Sociodemographic variation was explored by Poisson regression. Crude and directly standardized rates (for age, sex and ethnicity) were compared with pre-EIS rates from two major epidemiological FEP studies conducted in urban English settings.
A total of 285 cases met FEP diagnoses in CAMEO, yielding a crude incidence of 50 per 100 000 person-years [95% confidence interval (CI) 44.5-56.2]. Age- and sex-adjusted rates were raised for people from black ethnic groups compared with the white British [incidence rate ratio (IRR) 2.1, 95% CI 1.1-3.8]. Rates in our EIS were comparable with pre-EIS rates observed in more urban areas after age, sex and ethnicity standardization.
Our findings suggest that the incidence observed in EIS is far higher than originally anticipated and is comparable to rates observed in more urban settings prior to the advent of EIS. Sociodemographic variation due to ethnicity and other factors extend beyond urban populations. Our results have implications for psychosis aetiology and service planning.
Psychological Medicine 12/2010; 41(5):949-58. · 6.16 Impact Factor
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ABSTRACT: To describe symptom expression and functional outcome in psychotic disorders in relation with temperament traits assessed with the Temperament and Character Inventory (TCI) in a population-based sample.
As part of the 31-year follow-up survey of the Northern Finland 1966 Birth Cohort, TCI temperament items were filled in by 4349 members of the cohort. In individuals with psychotic disorders, also positive and negative symptoms and outcome variables were assessed in a 35-year follow-up. Information of TCI and outcomes were available for altogether 41 individuals with psychosis.
Reward dependence (RD) (rho=-0.45) and Persistence (P) (rho=-0.52) were significantly correlated with Positive and Negative Syndrome Scale (PANSS) negative symptoms. Higher P scores predicted higher social and occupational functioning (as measured by Social and Occupational Functioning Assessment Scale [SOFAS]), and higher Harm avoidance (HA) predicted a higher likelihood of being on a disability pension.
Results indicate that understanding of personality dimensions support better understanding of outcome and symptom expressions in psychotic disorders.
European Psychiatry 11/2009; 25(1):26-32. · 2.77 Impact Factor
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ABSTRACT: Abnormalities in reinforcement learning and reversal learning have been reported in psychosis, possibly secondary to subcortical dopamine abnormalities.
We studied simple discrimination (SD) learning and reversal learning in a sample of 119 first-episode psychosis patients from the Cambridge early psychosis service (CAMEO) and 107 control participants. We used data on reinforcement learning and reversal learning extracted from the Cambridge Neuropsychological Test Automated Battery Intradimensional-Extradimensional shift task, which measures cognitive flexibility but also involves simple reinforcement learning (SD learning) and reversal learning stages. We also gathered diagnostic information to examine whether there were any differences between patients ultimately diagnosed with schizophrenia-spectrum disorders and those diagnosed with affective psychosis.
Psychosis patients demonstrated deficits in simple reinforcement learning (SD learning) and in reversal learning, with no differences between affective psychosis and schizophrenia-spectrum psychosis. There was a significant modest correlation between reversal errors and negative symptoms (Spearman rho = 0.3, P = .02).
There are reinforcement learning abnormalities in first-episode psychosis, which correlate with negative symptoms, suggesting a possible role for orbitofrontal cortex and ventral striatal pathology in the pathogenesis of motivational deficits in psychosis.
Schizophrenia Bulletin 09/2008; 34(5):848-55. · 8.80 Impact Factor
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ABSTRACT: While dopamine systems have been implicated in the pathophysiology of schizophrenia and psychosis for many years, how dopamine dysfunction generates psychotic symptoms remains unknown. Recent theoretical interest has been directed at relating the known role of midbrain dopamine neurons in reinforcement learning, motivational salience and prediction error to explain the abnormal mental experience of psychosis. However, this theoretical model has yet to be explored empirically. To examine a link between psychotic experience, reward learning and dysfunction of the dopaminergic midbrain and associated target regions, we asked a group of first episode psychosis patients suffering from active positive symptoms and a group of healthy control participants to perform an instrumental reward conditioning experiment. We characterized neural responses using functional magnetic resonance imaging. We observed that patients with psychosis exhibit abnormal physiological responses associated with reward prediction error in the dopaminergic midbrain, striatum and limbic system, and we demonstrated subtle abnormalities in the ability of psychosis patients to discriminate between motivationally salient and neutral stimuli. This study provides the first evidence linking abnormal mesolimbic activity, reward learning and psychosis.
Molecular psychiatry 04/2008; 13(3):239, 267-76. · 15.05 Impact Factor
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ABSTRACT: Delusions are maladaptive beliefs about the world. Based upon experimental evidence that prediction error-a mismatch between expectancy and outcome--drives belief formation, this study examined the possibility that delusions form because of disrupted prediction--error processing. We used fMRI to determine prediction-error-related brain responses in 12 healthy subjects and 12 individuals (7 males) with delusional beliefs. Frontal cortex responses in the patient group were suggestive of disrupted prediction-error processing. Furthermore, across subjects, the extent of disruption was significantly related to an individual's propensity to delusion formation. Our results support a neurobiological theory of delusion formation that implicates aberrant prediction-error signalling, disrupted attentional allocation and associative learning in the formation of delusional beliefs.
Brain 10/2007; 130(Pt 9):2387-400. · 9.46 Impact Factor
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ABSTRACT: 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.
To examine the effects of ketamine in healthy people using a structured psychiatric interview.
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.
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.
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.
The British Journal of Psychiatry 09/2006; 189:173-9. · 6.62 Impact Factor
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ABSTRACT: Childhood neuromotor dysfunction is a risk factor for schizophrenia, a disorder in which cognitive deficits are prominent. The relationship between early neurodevelopment and adult cognition in schizophrenia remains unclear.
We examined the associations between infant motor development and adult cognitive functions in schizophrenia (n = 61) and the general population (n = 104) in a sample drawn from the The Northern Finland 1966 Birth Cohort. Data on ages of learning to stand and walk with or without support were obtained at age 12 months by health visitor assessment. Neurocognitive measures at age 33-35 included executive function, verbal and visual episodic memory, and visuo-spatial working memory.
The schizophrenia group achieved neuromotor milestones later and performed significantly worse than the control group on all measures of cognition. In pooled analyses there were associations between infant motor development and adult cognition in the domains of executive function, verbal learning and visuospatial working memory, but not in visual object learning. The pattern of associations between development and cognition was similar in schizophrenia and the general population.
These findings are consistent with the hypothesis that in schizophrenia mild infant motor developmental delay and adult cognitive deficits (at least in some domains) are age dependent manifestations of the same underlying neural process. Thus, they may be better considered as part of a single longitudinal syndrome.
Schizophrenia Research 02/2006; 81(1):65-74. · 4.75 Impact Factor
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ABSTRACT: The relationship between the age of reaching infant developmental milestones and later intellectual function within the normal population remains unresolved. We hypothesised that the age of learning to stand in infancy would be associated with adult executive function and that the association would be apparent throughout the range of abilities, rather than confined to extremes.
The Northern Finland 1966 Birth Cohort is based upon 12,058 live-born children in a geographic and temporally defined population. Information on age at learning to stand without support was obtained at one year. At age 33-35 a random sample of 104 subjects underwent a neuropsychological test battery including tests of executive function (cognitive categorisation), visuo-spatial memory, verbal learning and visual object learning. We investigated associations between developmental data and adult neuropsychological test scores.
There was a significant linear relationship between age of learning to stand and adult categorisation: the earlier the attainment of the milestone, the better was the categorisation. No such relationships were observed between infant neurodevelopment and adult cognition in other neuropsychological domains.
Even within the normal range of development, early development in the gross motor domain is associated with better adult executive function (in tests of categorisation). Investigation of the determinants and sequelae of normal neural development will facilitate research into a variety of neurodevelopmental disorders.
Journal of Child Psychology and Psychiatry 02/2006; 47(1):25-9. · 4.28 Impact Factor
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ABSTRACT: 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.
The British Journal of Psychiatry 05/2004; 184:357-8. · 6.62 Impact Factor
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ABSTRACT: The question of whether prenatal exposure to influenza epidemics is associated with an increased risk of later schizophrenia remains controversial. The authors examined this relationship, using data on the dates of birth and gender of 3,827 schizophrenic patients born in England and Wales between 1938 and 1965 and first admitted to hospitals in the 1980s, the numbers of live births between 1938 and 1965, and the numbers of deaths attributed to influenza between 1937 and 1965. The analysis showed that females, but not males, exposed to influenza epidemics 5 months before birth had a significantly greater rate of adult schizophrenia.
American Journal of Psychiatry 02/1994; 151(1):117-9. · 12.54 Impact Factor
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ABSTRACT: We examined the relationship between the dates of births of schizophrenic patients admitted to hospitals for the first time in England and Wales between 1970 and 1979, and the occurrence of influenza epidemics between 1939 and 1960. Our results indicate that exposure to influenza epidemics between the third and seventh month of gestation is associated with schizophrenia in adult life. The hypothesis that maternal viral infection is an important cause of schizophrenia can explain many aspects of the enigmatic epidemiology of the condition.
The British Journal of Psychiatry 05/1992; 160:461-6. · 6.62 Impact Factor
