Biomedical subjects

Paul Fearon

Publications and source records attributed to Paul Fearon.

At least 19 recordsLinked to original sources

PubMed2007

Parental separation, loss and psychosis in different ethnic groups: a case-control study.

BACKGROUND: Numerous studies have reported high rates of psychosis in the Black Caribbean and Black African populations in the UK. However, few studies have investigated the role of specific risk factors in different ethnic groups. We sought to investigate the relationship between long-term separation from, and death of, a parent before the age of 16 and risk of adult psychosis in different ethnic groups. METHOD: All patients with a first episode of psychosis who made contact with psychiatric services in defined catchment areas in London and Nottingham, UK and a series of community controls were included in the AESOP (Aetiology and Ethnicity in Schizophrenia and Other Psychoses) study. Data relating to clinical and social variables, including parental separation and loss, were collected from patients and controls. RESULTS: Separation from, and death of, a parent before the age of 16 were both strongly associated with a two- to threefold increased risk of psychosis. The strength of these associations were similar for White British and Black Caribbean (but not Black African) subjects. Separation from (but not death of) a parent was more common among Black Caribbean controls than White British controls. CONCLUSIONS: Early separation may have a greater impact in the Black Caribbean population, because it is more common, and may contribute to the excess of psychosis in this population.

Adolescent↗

PubMed2006

Incidence of schizophrenia and other psychoses in ethnic minority groups: results from the MRC AESOP Study.

BACKGROUND: The incidence of schizophrenia in the African-Caribbean population in England is reported to be raised. We sought to clarify whether (a) the rates of other psychotic disorders are increased, (b) whether psychosis is increased in other ethnic minority groups, and (c) whether particular age or gender groups are especially at risk. METHOD: We identified all people (n=568) aged 16-64 years presenting to secondary services with their first psychotic symptoms in three well-defined English areas (over a 2-year period in Southeast London and Nottingham and a 9-month period in Bristol). Standardized incidence rates and incidence rate ratios (IRR) for all major psychosis syndromes for all main ethnic groups were calculated. RESULTS: We found remarkably high IRRs for both schizophrenia and manic psychosis in both African-Caribbeans (schizophrenia 9.1, manic psychosis 8.0) and Black Africans (schizophrenia 5.8, manic psychosis 6.2) in men and women. IRRs in other ethnic minority groups were modestly increased as were rates for depressive psychosis and other psychoses in all minority groups. These raised rates were evident in all age groups in our study. CONCLUSIONS: Ethnic minority groups are at increased risk for all psychotic illnesses but African-Caribbeans and Black Africans appear to be at especially high risk for both schizophrenia and mania. These findings suggest that (a) either additional risk factors are operating in African-Caribbeans and Black Africans or that these factors are particularly prevalent in these groups, and that (b) such factors increase risk for schizophrenia and mania in these groups.

Adolescent↗

PubMed2006

Environmental factors in schizophrenia: the role of migrant studies.

There is now compelling evidence that migrant groups in several countries have an elevated risk of developing schizophrenia and other psychotic disorders. Though the findings of earlier studies were greeted with skepticism, and ascribed by some to have methodological shortcomings and diagnostic biases, the more rigorous recent studies, from a variety of countries, have still found markedly increased incidence rates. While this phenomenon is an important health issue in its own right, understanding the reasons for the increased rates may provide valuable insights into the causes of schizophrenia and other psychotic disorders in general. The challenge for the next phase of studies is to identify the relevant risk factors and how they might interact to increase the risk of psychosis, both in migrant groups and in the general population.

Humans↗

PubMed2006

Gray matter abnormalities associated with duration of untreated psychosis.

PURPOSE: A long duration of untreated psychosis (DUP) is associated with relatively poor clinical and social outcomes. In order to identify whether an anatomically mediated mechanism may give rise to poorer outcomes, it is important to identify whether a long DUP is associated with greater brain structural abnormalities. METHOD: 81 patients with first-episode psychosis (schizophrenia, affective, and other psychoses) were scanned using high resolution Magnetic Resonance Imaging. DUP was defined as the number of days between first onset of psychotic symptoms and first contact with mental health services. High-resolution MRI images and voxel-based methods of image analysis were used to investigate brain structure in these patients. RESULTS: Longer DUP was associated with gray matter reductions in left middle and inferior temporal, left occipital and left fusiform cortices, and with gray matter excess of the left basal ganglia. All findings remained significant when co-varying for exposure to antipsychotic treatment. CONCLUSIONS: Temporal gray matter reductions are more marked in patients with a long DUP. This could reflect a progressive pathological process that is active prior to treatment. Alternatively, these abnormalities could be associated with a more insidious onset of illness and a later presentation to services.

Adolescent↗

PubMed2006

Heterogeneity in incidence rates of schizophrenia and other psychotic syndromes: findings from the 3-center AeSOP study.

CONTEXT: Convention suggests uniformity of incidence of schizophrenia and other psychoses; variation would have implications for their causes and biological characteristics. OBJECTIVE: To investigate variability in the incidence of psychotic syndromes in terms of place, ethnicity, age, and sex. DESIGN: Three-center, prospective, comprehensive survey of clinically relevant first-onset psychotic syndromes over a 2-year period (1997-1999). Census data provided the denominator. SETTING: Southeast London, Nottingham, and Bristol, England. PARTICIPANTS: One million six hundred thousand person-years yielded 568 subjects aged 16 to 64 years with clinically relevant psychotic syndromes. MAIN OUTCOME MEASURES: The World Health Organization Psychosis Screen and the Schedules for Clinical Assessment in Neuropsychiatry to classify, blind to ethnicity, all DSM-IV psychotic syndromes and the subclasses of schizophrenia, other nonaffective disorders, affective disorders, and substance-induced psychosis. RESULTS: All syndromes showed a characteristic age distribution. Schizophrenia was significantly more common in men (incidence rate ratio [IRR], 2.3 [95% confidence interval (CI), 1.7-3.1]); affective disorders occurred equally in men and women (IRR, 1.0 [95% CI, 0.7-1.3]). All psychoses were more common in the black and minority ethnic group (crude IRR, 3.6 [95% CI, 3.0-4.2]). Differences in age, sex, and study center accounted for approximately a quarter of this effect (adjusted IRR, 2.9 [95% CI, 2.4-3.5]) in each psychosis outcome. The age-sex standardized incidence rate for all psychoses was higher in Southeast London (IRR, 49.4 [95% CI, 43.6-55.3]) than Nottingham (IRR, 23.9 [95% CI, 20.6-27.2]) or Bristol (IRR, 20.4 [95% CI, 15.1-25.7]). Rates of all outcomes except affective disorders remained significantly higher in Southeast London when the model was expanded to control for ethnicity. CONCLUSIONS: There is significant and independent variation of incidence of schizophrenia and other psychoses in terms of sex, age, ethnicity, and place. This confirms that environmental effects at the individual, and perhaps neighborhood level, may interact together and with genetic factors in the etiology of psychosis.

Adolescent↗

PubMed2006

Social outcomes in schizophrenia: from description to action.

PURPOSE OF REVIEW: The reality of schizophrenia is not fully expressed by measures of psychopathology and both descriptive research and research into interventions benefit from the investigation of social outcomes. We define these as measures which reflect performance compared to normal social expectations, either of oneself or of another. The studies we reviewed looked at the effects on summary measures, for example, quality of life, as well as simpler, more self-explanatory outcomes such as employment, marital status, financial independence and housing. RECENT FINDINGS: The review contrasts studies which describe the determinants of social outcomes and studies designed to estimate the effects of interventions on these outcomes. Recent descriptive studies demonstrate that social outcomes have both longitudinal and cross-sectional associations with cognitive impairment, preexisting functional impairment and certain symptoms. Studies of both pharmacological and social interventions suggest that, at best, these can affect social outcomes. SUMMARY: Simpler social outcomes are reported less frequently than summary measures which can make interpretation more difficult, thus diluting a potential advantage of social outcome measures to researchers and clinicians alike. Social outcomes are underreported compared to measures of psychopathology, particularly in trials of interventions.

Employment↗

PubMed2006

Clinical and social determinants of duration of untreated psychosis in the AESOP first-episode psychosis study.

BACKGROUND: Despite considerable research investigating the relationship between a long duration of untreated psychosis (DUP) and outcomes, there has been much less considering predictors of a long DUP. AIMS: To investigate the clinical and social determinants of DUP in a large sample of patients with a first episode of psychosis. METHOD: All patients with a first episode of psychosis who made contact with psychiatric services over a 2-year period and were living in defined catchment areas in London and Nottingham, UK were included in the AESOP study. Data relating to clinical and social variables and to DUP were collected from patients, relatives and case notes. RESULTS: An insidious mode of onset was associated with a substantially longer DUP compared with an acute onset, independent of other factors. Unemployment had a similar, if less strong, effect. Conversely, family involvement in help-seeking was independently associated with a shorter duration. There was weak evidence that durations were longer in London than in Nottingham. CONCLUSIONS: These findings suggest that DUP is influenced both by aspects of the early clinical course and by the social context.

Adolescent↗

PubMed2006

First episode psychosis and ethnicity: initial findings from the AESOP study.

In this paper we provide an overview of the design and the initial findings of the AESOP (Aetiology and Ethnicity in Schizophrenia and Other Psychoses) study. The AESOP study is a major multi-centre incidence and case-control study conducted in the UK. Its primary aim is to investigate the high rates of psychosis in African-Caribbean populations from the UK, and from this to shed light on the aetiology of psychosis in general. As the study has progressed, the wealth of data collected has allowed further questions to be addressed: for example, about determinants of duration of untreated psychosis. Initial findings relating to incidence rates and between-case comparisons are presented. Future planned analyses are outlined and details of a follow-up of the AESOP cohort and ongoing international collaborations are provided.

Journal Article↗

PubMed2005

Duration of untreated psychosis and ethnicity in the AESOP first-onset psychosis study.

BACKGROUND: There is a common assumption that Black patients with a psychotic mental illness experience longer treatment delays during a first episode. We sought to investigate this issue in a large cohort of patients with a first episode of psychosis. METHOD: All patients with a first episode of psychosis presenting to secondary mental health services within tightly defined catchment areas in south-east London and Nottingham over a 2-year period were included in the study. Data relating to duration of untreated psychosis (DUP) and clinical and sociodemographic characteristics were collected from patients, relatives and case-notes. RESULTS: There was no evidence that African-Caribbean or Black African patients experienced longer periods of untreated psychosis than White British patients prior to first contact with services. There was evidence that Black African patients experienced shorter periods of untreated psychosis than White British patients. CONCLUSIONS: Contrary to what is commonly assumed, our study suggests that Black patients with a psychotic mental illness do not experience longer treatment delays prior to first contact with services than White British patients. This suggests that strategies to reduce treatment delays targeted specifically at Black patients will be of limited value.

Adolescent↗

PubMed2005

The structural brain correlates of neurological soft signs in healthy individuals.

It has yet to be established whether neurological soft signs (NSS), which include poor motor coordination, sensory perceptual difficulties and difficulties in sequencing of complex motor tasks, result from specific or diffuse brain structural abnormalities. Studying the neuroanatomical basis of NSS in healthy individuals may help to identify which brain areas are specifically associated with these signs, while excluding the potential confounding effects of psychiatric and neurological disorders. We investigated the relationship between brain structure and NSS in 43 healthy individuals, using the Neurological Evaluation Scale for neurological assessment, and high resolution MRI and voxel-based methods of image analysis to investigate brain structure. Higher rates of NSS were associated with a reduction of inferior frontal gyrus, middle and superior temporal gyrus, and anterior cingulate gyrus. It is of note that in a previous study of patients with psychosis we found that an excess of NSS was associated with a reduction of similar cortical areas. Therefore, we suggest that these cortical brain structural changes represent a common neuroanatomical substrate of NSS, across healthy individuals and patients with psychosis.

Adolescent↗

PubMed2005

Dermatoglyphics and Schizophrenia: a meta-analysis and investigation of the impact of obstetric complications upon a-b ridge count.

BACKGROUND: Patients with schizophrenia show deviances in their dermatoglyphics, in particular reductions in palmar a-b ridge counts (ABRCs), which are evidence of an early developmental deviance. However, the severity or the origin of these ABRC changes has not been established. METHOD: (i) We examined the published literature on the ABRC in patients with schizophrenia against controls with a random effects meta-analysis. (ii) We used linear regression to study the ABRC in our sample of families including 125 patients with schizophrenia, 107 of their unaffected relatives and 98 controls. (iii) The effect of obstetric complications on the patient's ABRC was examined using the Lewis Murray scale. RESULTS: The pooled standardised effect size of ABRC differences between patients and controls obtained by our meta-analysis was 0.39 (95% CI: 0.05-0.73; p=0.03). In our sample, there were no significant differences in ABRCs between those with schizophrenia, their relatives and controls. Only those patients with obstetric complications had significantly reduced ABRC compared to controls (p=0.01). CONCLUSIONS: We confirmed the presence of significant yet mild ABRC reductions in schizophrenia. These represent a subtle deviance from the norm and could be present in certain subsets of patients, possibly those who suffered early developmental insults.

Dermatoglyphics↗

PubMed2005

Different effects of typical and atypical antipsychotics on grey matter in first episode psychosis: the AESOP study.

Typical antipsychotic drugs act on the dopaminergic system, blocking the dopamine type 2 (D2) receptors. Atypical antipsychotics have lower affinity and occupancy for the dopaminergic receptors, and a high degree of occupancy of the serotoninergic receptors 5-HT2A. Whether these different pharmacological actions produce different effects on brain structure remains unclear. We explored the effects of different types of antipsychotic treatment on brain structure in an epidemiologically based, nonrandomized sample of patients at the first psychotic episode. Subjects were recruited as part of a large epidemiological study (AESOP: aetiology and ethnicity in schizophrenia and other psychoses). We evaluated 22 drug-free patients, 32 on treatment with typical antipsychotics and 30 with atypical antipsychotics. We used high-resolution MRI and voxel-based methods of image analysis. The MRI analysis suggested that both typical and atypical antipsychotics are associated with brain changes. However, typicals seem to affect more extensively the basal ganglia (enlargement of the putamen) and cortical areas (reductions of lobulus paracentralis, anterior cingulate gyrus, superior and medial frontal gyri, superior and middle temporal gyri, insula, and precuneus), while atypical antipsychotics seem particularly associated with enlargement of the thalami. These changes are likely to reflect the effect of antipsychotics on the brain, as there were no differences in duration of illness, total symptoms scores, and length of treatment among the groups. In conclusion, we would like to suggest that even after short-term treatment, typical and atypical antipsychotics may affect brain structure differently.

Adolescent↗

PubMed2005

Increased pituitary volume in antipsychotic-free and antipsychotic-treated patients of the AEsop first-onset psychosis study.

Subjects at their first psychotic episode show an enlarged volume of the pituitary gland, but whether this is due to hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, or to stimulation of the prolactin-secreting cells by antipsychotic treatment, is unclear. We measured pituitary volume, using 1.5-mm, coronal, 1.5 T, high-resolution MRI images, in 78 patients at the first psychotic episode and 78 age- and gender-matched healthy controls. In all, 18 patients were antipsychotic-free (12 of these were antipsychotic-naïve), 26 were receiving atypical antipsychotics, and 33 were receiving typical antipsychotics. As hypothesized, patients had a larger pituitary volume than controls (+22%, p< 0.001). When divided by antipsychotic treatment, and compared to controls, the pituitary volume was 15% larger in antipsychotic-free patients (p=0.028), 17% larger in patients receiving atypicals (p=0.01), and 30% larger in patients receiving typicals (p<0.001). Patients receiving typicals not only had the largest pituitary volume compared to controls but also showed a trend for a larger pituitary volume compared to the other patients grouped together (+11%, p=0.08). When divided by diagnosis, and compared to controls, the pituitary volume was 24% larger in patients with schizophrenia/schizophreniform disorder (n=40, p<0.001), 19% larger in depressed patients (n=13, p=0.022), 16% larger in bipolar patients (n=16, p=0.037), and 12% larger in those with other psychoses (n=9, p=0.2). In conclusion, the first-episode of a psychotic disorder is associated with a larger pituitary independently of the presence of antipsychotic treatment, and this could be due to activation of the HPA axis. Typical antipsychotics exert an additional enlarging effect on pituitary volume, likely to be related to activation of prolactin-secreting cells. This activation of the hormonal stress response could participate to the important metabolic abnormalities observed in patients with psychosis.

Adolescent↗

PubMed2005

Gender differences in incidence and age at onset of mania and bipolar disorder over a 35-year period in Camberwell, England.

OBJECTIVE: Despite clear gender differences in the symptoms and course of bipolar affective disorder, studies investigating age at onset by gender have yielded inconsistent results. The authors investigated gender differences in age at onset and incidence of first-episode mania and bipolar disorder in an epidemiological catchment area in southeast London over a 35-year period. METHOD: All adult cases of first-episode psychosis, mania, or hypomania presenting to services in Camberwell, southeast London (1965-1999), were identified. Computerized diagnoses for these cases were generated by using the Operational Checklist for Psychotic Disorders program. Incidence rates and rate ratios of DSM-IV bipolar I disorder, first manic episode, by gender and age (10-year age-at-onset categories) were calculated. Differences in age at onset of first-episode mania and bipolar disorder by gender were examined by using univariate and multivariate analyses. RESULTS: Men had a significantly earlier onset of first-episode mania and bipolar disorder, with childhood antisocial behavior also being significantly associated, after multivariate analysis. Women had higher incidence rates of bipolar I disorder throughout adult life, except for early life (ages 16-25 years), although gender differences in individual age bands did not reach statistical significance. CONCLUSIONS: Men appear to have an earlier onset of mania and bipolar disorder than women. The association of male gender and childhood antisocial behavior with early-onset bipolar disorder raised the possibility of the existence of an early-onset subgroup.

Adolescent↗

PubMed2005

Incidence of bipolar affective disorder in three UK cities: results from the AESOP study.

BACKGROUND: There has been a relative dearth of epidemiological research into bipolar affective disorder. Furthermore, incidence studies of bipolar disorder have been predominantly retrospective and most only included hospital admission cases. AIMS: To determine the incidence of operationally defined bipolar disorder in three areas of the UK and to investigate any differences in gender and ethnicity. METHOD: All patients who contacted mental health services with first-episode psychosis or non-psychotic mania between September 1997 and August 1999 were identified and diagnosed according to ICD-10 criteria. Incidence rates of bipolar affective disorder were standardised for age and stratified by gender and ethnic group across the three areas. RESULTS: The incidence rate per 100,000 per year in south-east London was over twice that in Nottingham and Bristol. There was no significant difference in the rates of disorder in men and women. Incidence rates of bipolar disorder in the combined Black and minority ethnic groups in all three areas were significantly higher than those of the comparison White groups. CONCLUSIONS: The incidence of bipolar disorder was higher in south-east London than in the other two areas, and was higher among Black and minority ethnic groups than in the White population.

Adolescent↗

PubMed2004

Effects of very low birthweight on brain structure in adulthood.

Very-low-birthweight (VLBW) individuals are at high risk of brain injury in the perinatal period. We wished to determine how such early brain lesions affect brain structure in adulthood. Thirty-two VLBW adults (20 female, 12 male) and 18 term, normal birthweight sibling control individuals (nine female, nine male) underwent structural MRI at a mean age of 23 years 4 months (range 17 to 33 years; SD 3.4). Images were analyzed using an automated tissue segmentation algorithm in order to estimate whole brain tissue class volumes in native space. Images were then warped to a template image in standard space. There was no significant between-group difference in whole brain, grey matter, white matter, or total cerebral spinal fluid (CSF) volumes. However, lateral ventricular volume was significantly increased by 41% in those with VLBW. The ratio of grey to white matter was also significantly increased (by 10%) in those with VLBW. Group comparison maps showed widespread changes in the distribution of grey and white matter, and relative excess of ventricular CSF, in the brains of VLBW individuals. Increased ventricular volume predicted decreased grey matter in subcortical nuclei and limbic cortical structures, and decreased periventricular white matter. We conclude that these diffuse abnormalities of grey and white matter are a consequence of the interaction of perinatal brain injury and ongoing neurodevelopmental processes.

Adolescent↗

PubMed2004

Brain volumes in adult survivors of very low birth weight: a sibling-controlled study.

OBJECTIVES: To establish whether adults who were born very low birth weight (VLBW) show altered volumes of certain brain structures. METHODS: Unmatched case-control study was conducted of 33 individuals from a cohort of VLBW (<1500 g) infants who were born between 1966 and 1977 and 18 of their normal birth weight siblings. Whole brain, gray matter, ventricular, corpus callosum, and hippocampal volumes were measured on structural magnetic resonance imaging scans. RESULTS: VLBW individuals had a 46% increase in total ventricular volume and a 17% reduction in posterior corpus callosum volume. No differences in whole brain, gray matter, or hippocampal volumes were observed. CONCLUSION: Specific differences exist in the volumes of certain brain structures in adults who were born VLBW compared with their normal birth weight siblings.

Adult↗

PubMed2003

The structural brain correlates of neurological soft signs in AESOP first-episode psychoses study.

Patients with schizophrenia and related psychoses have an excess of minor neurological abnormalities (neurological soft signs) of unclear neuropathological origin. These include poor motor coordination, sensory perceptual difficulties and difficulties in sequencing complex motor tasks. Neurological soft signs seem not to reflect primary tract or nuclear pathology. It still has to be established whether neurological soft signs result from specific or diffuse brain structural abnormalities. Studying their anatomical correlates can provide not only a better understanding of the aetiopathogenesis of soft signs, but also of the pathophysiology of schizophrenia. Surprisingly few studies have investigated the brain correlates of neurological soft signs. In the present study, we investigated the relationship between brain structure and neurological soft signs in an epidemiologically based sample of 77 first-episode psychosis patients. We used the Neurological Evaluation Scale for neurological assessment and high-resolution MRI and voxel-based methods of image analysis to investigate brain structure. Higher rates of soft neurological signs (both motor and sensory) were associated with a reduction of grey matter volume of subcortical structures (putamen, globus pallidus and thalamus). Signs of sensory integration deficits were additionally associated with volume reduction in the cerebral cortex, including the precentral, superior and middle temporal, and lingual gyri. Neurological soft signs and their associated brain changes were independent of antipsychotic exposure. We conclude that neurological soft signs are associated with regional grey matter volume changes and that they may represent a clinical sign of the perturbed cortical-subcortical connectivity that putatively underlies psychotic disorders.

Adolescent↗