Stanley Zammit

University of Bristol, Bristol, England, United Kingdom

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Publications (123)992.34 Total impact

  • Maria Niarchou, Stanley Zammit, Glyn Lewis
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    ABSTRACT: The purpose of this study is to highlight the Avon Longitudinal Study of Parents and Children (ALSPAC) as a resource to study psychopathology. To demonstrate this, we review the studies related to depression and psychosis in childhood and adolescence and discuss the results in relation to the aetiology of depression and psychotic experiences (PEs) and possible underlying mechanisms. We examined the list of publications from ALSPAC and then classified them as examining (a) the course and risk factors of maternal and paternal depression, (b) the effects of maternal and paternal depression on child development, (c) risk factors for depression in childhood and adolescence, (d) the frequency, clinical relevance and risk factors of PEs, and (e) shared risk factors for depression and PEs. There was evidence that environmental stressors and the way these are interpreted contribute to risk of depression and evidence that biological factors related to puberty are also likely to play a role. With regards to PEs, the findings further support the existence of 'a continuum of psychosis' while they also suggest that PEs might be of limited clinical utility in predicting psychotic disorder during adolescence and early adulthood. Finally, most risk factors examined were found to be shared between depression and PEs. The ALSPAC birth cohort has provided important insights for our understanding of the aetiological mechanisms underlying depression and PEs. Future research could aim to incorporate measures of automatic psychological mechanisms to provide insights into the brain mechanisms that underlie these clinical phenomena.
    Social Psychiatry 05/2015; DOI:10.1007/s00127-015-1072-8 · 2.58 Impact Factor
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    ABSTRACT: Background Sleep disturbances are commonly reported in the psychosis prodrome, but rarely explored in relation to psychotic experiences. Aims To investigate the relationship between specific parasomnias (nightmares, night terrors and sleepwalking) in childhood and later adolescent psychotic experiences. Method The sample comprised 4720 individuals from a UK birth cohort. Mothers reported on children's experience of regular nightmares at several time points between 2 and 9 years. Experience of nightmares, night terrors and sleepwalking was assessed using a semi-structured interview at age 12. Psychotic experiences were assessed at ages 12 and 18 using a semi-structured clinical interview. Results There was a significant association between the presence of nightmares at 12 and psychotic experiences at 18 when adjusted for possible confounders and psychotic experiences at 12 (OR = 1.62, 95% CI 1.19-2.20). The odds ratios were larger for those who reported persistent psychotic experiences. Conclusions The presence of nightmares might be an early risk indicator for psychosis. © The Royal College of Psychiatrists 2015.
    The British journal of psychiatry: the journal of mental science 05/2015; DOI:10.1192/bjp.bp.113.144089 · 7.34 Impact Factor
  • PLoS ONE 04/2015; 10(4):e0122896. DOI:10.1371/journal.pone.0122896 · 3.53 Impact Factor
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    ABSTRACT: Schizophrenia is often regarded as a "dysconnectivity" disorder and recent work using graph theory has been used to better characterize dysconnectivity of the structural connectome in schizophrenia. However, there are still little data on the topology of connectomes in less severe forms of the condition. Such analysis will identify topological markers of less severe disease states and provide potential predictors of further disease development. Individuals with psychotic experiences (PEs) were identified from a population-based cohort without relying on participants presenting to clinical services. Such individuals have an increased risk of developing clinically significant psychosis. 123 individuals with PEs and 125 controls were scanned with diffusion-weighted MRI. Whole-brain structural connectomes were derived and a range of global and local GT-metrics were computed. Global efficiency and density were significantly reduced in individuals with PEs. Local efficiency was reduced in a number of regions, including critical network hubs. Further analysis of functional subnetworks showed differential impairment of the default mode network. An additional analysis of pair-wise connections showed no evidence of differences in individuals with PEs. These results are consistent with previous findings in schizophrenia. Reduced efficiency in critical core hubs suggests the brains of individuals with PEs may be particularly predisposed to dysfunction. The absence of any detectable effects in pair-wise connections illustrates that, at less severe stages of psychosis, white-matter alterations are subtle and only manifest when examining network topology. This study indicates that topology could be a sensitive biomarker for early stages of psychotic illness. Hum Brain Mapp, 2015.© 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Human Brain Mapping 04/2015; DOI:10.1002/hbm.22796 · 6.92 Impact Factor
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    ABSTRACT: It has been suggested that those who both bully and are victims of bullying (bully/victims) are at the highest risk of adverse mental health outcomes. However, unknown is whether most bully/victims were bullies or victims first and whether being a bully/victim is more detrimental to mental health than being a victim. A total of 4101 children were prospectively studied from birth, and structured interviews and questionnaires were used to assess bullying involvement at 10 years (elementary school) and 13 years of age (secondary school). Mental health (anxiety, depression, psychotic experiences) was assessed at 18 years. Most bully/victims at age 13 (n = 233) had already been victims at primary school (pure victims: n = 97, 41.6 % or bully/victims: n = 47, 20.2 %). Very few of the bully/victims at 13 years had been pure bullies previously (n = 7, 3 %). After adjusting for a wide range of confounders, both bully/victims and pure victims, whether stable or not from primary to secondary school, were at increased risk of mental health problems at 18 years of age. In conclusion, children who are bully/victims at secondary school were most likely to have been already bully/victims or victims at primary school. Children who are involved in bullying behaviour as either bully/victims or victims at either primary or secondary school are at increased risk of mental health problems in late adolescence regardless of the stability of victimization. Clinicians should consider any victimization as a risk factor for mental health problems.
    European Child & Adolescent Psychiatry 04/2015; DOI:10.1007/s00787-015-0705-5 · 3.55 Impact Factor
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    ABSTRACT: Offspring of mothers with depression are a high-risk group for the development of suicide-related behavior. These offspring are therefore a priority for preventive interventions; however, pathways contributing to risk, including specific aspects of offspring psychopathology, remain unclear. The aim of this study was to examine whether offspring symptoms of major depressive disorder (MDD), generalized anxiety disorder (GAD), disruptive behavior disorder (DBD), attention-deficit/hyperactivity disorder (ADHD), and alcohol abuse independently mediate the association between maternal depression and offspring suicide-related behavior. Data were used from a population-based birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Three distinct classes of depression symptoms across the mothers' first 11 years of their child's life were identified (minimal, moderate, chronic-severe). Offspring psychopathology was assessed at age 15 years and suicide-related behavior at age 16 years. Data were analyzed using structural equation modeling. There was evidence for increased risk of suicidal ideation in offspring of mothers with chronic-severe depression symptoms in comparison to offspring of mothers with minimal symptoms (odds ratio = 3.04, 95% CI = 2.19, 4.21). This association was independently mediated by offspring MDD, GAD, and DBD symptoms. The same mechanisms were found for offspring of mothers with moderate depression symptoms over time. Results were similar for offspring suicide attempt except for additional evidence of an indirect effect through offspring ADHD symptoms. Findings highlight that suicide prevention efforts in offspring of mothers with depression should not only be targeted at offspring with MDD; it is also important to consider offspring with other forms of psychopathology. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.
    Journal of the American Academy of Child & Adolescent Psychiatry 02/2015; 47(5). DOI:10.1016/j.jaac.2015.02.006 · 6.35 Impact Factor
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    Molecular Psychiatry 02/2015; 20(2):207-214. DOI:10.1038/mp.2013.195 · 15.15 Impact Factor
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    ABSTRACT: Genetic risk prediction has several potential applications in medical research and clinical practice and could be used, for example, to stratify a heterogeneous population of patients by their predicted genetic risk. However, for polygenic traits, such as psychiatric disorders, the accuracy of risk prediction is low. Here we use a multivariate linear mixed model and apply multi-trait genomic best linear unbiased prediction for genetic risk prediction. This method exploits correlations between disorders and simultaneously evaluates individual risk for each disorder. We show that the multivariate approach significantly increases the prediction accuracy for schizophrenia, bipolar disorder, and major depressive disorder in the discovery as well as in independent validation datasets. By grouping SNPs based on genome annotation and fitting multiple random effects, we show that the prediction accuracy could be further improved. The gain in prediction accuracy of the multivariate approach is equivalent to an increase in sample size of 34% for schizophrenia, 68% for bipolar disorder, and 76% for major depressive disorders using single trait models. Because our approach can be readily applied to any number of GWAS datasets of correlated traits, it is a flexible and powerful tool to maximize prediction accuracy. With current sample size, risk predictors are not useful in a clinical setting but already are a valuable research tool, for example in experimental designs comparing cases with high and low polygenic risk. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    The American Journal of Human Genetics 01/2015; DOI:10.1016/j.ajhg.2014.12.006 · 10.99 Impact Factor
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    ABSTRACT: To determine neurocognitive, educational, and psychological functioning during childhood and early adolescence among survivors of early life meningitis who are apparently healthy. In the general population-based Avon Longitudinal Study of Parents and Children birth cohort, meningitis exposure was determined at age of 18 months. The outcomes of intelligence quotient, short-term memory, working memory, reading and spelling abilities, psychological and behavioral problems, depressive and anxiety symptoms, and psychotic experiences at ages 9 to 13 years were compared between those exposed and unexposed to meningitis. Individuals with special educational needs were excluded. By age of 18 months, 67 of 11,035 children were reported to have suffered from meningitis (0.61%). These children, compared with the unexposed, performed worse on all neurocognitive and educational measures; mean difference in total intelligence quotient 7.36 (95% confidence interval, 1.60-13.11). Meningitis was associated with higher depressive and anxiety symptoms (P = .02), psychological and behavioral problems (P = .09), and increased risk of psychotic experiences; risk ratio 2.22 (95% confidence interval, 1.12-4.38). Exposure to meningitis in the early life is associated with neurocognitive, educational, and psychological difficulties during childhood and early adolescence among survivors who are apparently healthy. Therefore, focusing only on serious neurologic disabilities may underestimate the true impact of early life meningitis. Copyright © 2015 Elsevier Inc. All rights reserved.
    Annals of Epidemiology 11/2014; 25(4). DOI:10.1016/j.annepidem.2014.11.013 · 2.15 Impact Factor
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    ABSTRACT: Psychotic phenomena are common in the general population but are excluded from diagnostic criteria for mild to moderate depression and anxiety despite their co-occurrence and shared risk factors. We used item response theory modelling to examine whether the co-occurrence of depressive, anxiety and psychotic phenomena is best explained by: (1) a single underlying factor; (2) two separate, uncorrelated factors; (3) two separate yet linked factors; or (4) two separate domains along with an underlying 'common mental distress' (CMD) factor. We defined where, along any latent continuum, the psychopathological items contributed most information.
    Psychological Medicine 11/2014; 45(07):1-11. DOI:10.1017/S003329171400261X · 5.43 Impact Factor
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    ABSTRACT: Individuals at clinical high risk (CHR) of developing psychosis present with widespread functional abnormalities in the brain. Cognitive deficits, including working memory (WM) problems, as commonly elicited by n-back tasks, are observed in CHR individuals. However, functional MRI (fMRI) studies, comprising a heterogeneous cluster of general and social cognition paradigms, have not necessarily demonstrated consistent and conclusive results in this population. Hence, a comprehensive review of fMRI studies, spanning almost one decade, was carried out to observe for general trends with respect to brain regions and cognitive systems most likely to be dysfunctional in CHR individuals. 32 studies were included for this review, out of which 22 met the criteria for quantitative analysis using activation likelihood estimation (ALE). Task related contrast activations were firstly analysed by comparing CHR and healthy control participants in the total pooled sample, followed by a comparison of general cognitive function studies (excluding social cognition paradigms), and finally by only looking at n-back working memory task based studies. Findings from the ALE implicated four key dysfunctional and distinct neural regions in the CHR group, namely the right inferior parietal lobule (rIPL), the left medial frontal gyrus (lmFG), the left superior temporal gyrus (lSTG) and the right fronto-polar cortex (rFPC) of the superior frontal gyrus (SFG). Narrowing down to relatively few significant dysfunctional neural regions is a step forward in reducing the apparent ambiguity of overall findings, which would help to target specific neural regions and pathways of interest for future research in CHR populations.
    Journal of Psychiatric Research 09/2014; 61. DOI:10.1016/j.jpsychires.2014.08.018 · 4.09 Impact Factor
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    ABSTRACT: The aim of the study was to determinate whether schizophrenia patients with a history of cannabis use have a different prognosis, with regards to readmission and hospital duration, compared with those without a history of cannabis use.
    Psychological Medicine 09/2014; 44(12):2513-2521. DOI:10.1017/S0033291714000191 · 5.43 Impact Factor
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    ABSTRACT: An argument often used to support the view that psychotic experiences (PEs) in general population samples are a valid phenotype for studying the aetiology of schizophrenia is that risk factors for schizophrenia show similar patterns of association with PEs. However, PEs often co-occur with depression, and no study has explicitly tested whether risk factors for schizophrenia are shared between PEs and depression, or are psychopathology specific, while jointly modelling both outcomes.
    Psychological Medicine 09/2014; 44(12):2557-2566. DOI:10.1017/S0033291714000026 · 5.43 Impact Factor
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    ABSTRACT: Rutter's commentary (Rutter, 2014) on our article (Munafò et al., 2014) provides us the opportunity to clarify some issues that he (and therefore, we suspect, others) may have misunderstood.
    Journal of Child Psychology and Psychiatry 08/2014; 55(10). DOI:10.1111/jcpp.12308 · 5.67 Impact Factor
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    ABSTRACT: Background: Several studies suggest a link between early-life infection and adult schizophrenia. Cross-sectional studies have reported: (1) increased prevalence of Epstein-Barr Virus (EBV), a member of the Herpesviridae family in schizophrenia; (2) a possible role of Herpes simplex virus in cognitive dysfunction in schizophrenia and healthy controls. We report a longitudinal serological study of early-life EBV infection, childhood IQ, and subsequent risk of psychotic experiences (PE) in adolescence. Methods: Serum antibodies to EBV (anti-VCA IgG) were measured in 530 participants from the ALSPAC cohort at age 4 years. Assessments for IQ at age 9 and PE at age 13 were attended by 401 and 366 of these individuals, respectively. Logistic regression calculated odds ratio (OR) for PE in EBV-exposed, compared with unexposed group. Mean IQ scores were compared between these groups; effect of IQ on the EBV-PE association was examined. Potential confounders included age, gender, ethnicity, social class, household crowding, and concurrent depression and anxiety. Results: About 25% of the sample was exposed to EBV at age 4. EBV exposure was associated with subsequent risk of definite PE in adolescence; OR 5.37 (95% CI 1.71-16.87), which remained significant after confounding adjustment. EBV-exposed individuals compared with unexposed performed worse on all IQ measures; mean difference in full-scale IQ 4.15 (95% CI 0.44-7.87); however, this was explained by socio-demographic differences. The EBV-PE association was not explained by IQ. Conclusions: Early-life exposure to EBV is associated with PE in adolescence, consistent with a role of infection/immune dysfunction in the aetiology of psychosis. (C) 2014 Published by Elsevier B.V.
    Schizophrenia Research 07/2014; 158(1-3). DOI:10.1016/j.schres.2014.05.019 · 4.43 Impact Factor
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    ABSTRACT: IMPORTANCE We investigated the variation in neuropsychological function explained by risk alleles at the psychosis susceptibility gene ZNF804A and its interacting partners using single nucleotide polymorphisms (SNPs), polygenic scores, and epistatic analyses. Of particular importance was the relative contribution of the polygenic score vs epistasis in variation explained. OBJECTIVES To (1) assess the association between SNPs in ZNF804A and the ZNF804A polygenic score with measures of cognition in cases with psychosis and (2) assess whether epistasis within the ZNF804A pathway could explain additional variation above and beyond that explained by the polygenic score. DESIGN, SETTING, AND PARTICIPANTS Patients with psychosis (n = 424) were assessed in areas of cognitive ability impaired in schizophrenia including IQ, memory, attention, and social cognition. We used the Psychiatric GWAS Consortium 1 schizophrenia genome-wide association study to calculate a polygenic score based on identified risk variants within this genetic pathway. Cognitive measures significantly associated with the polygenic score were tested for an epistatic component using a training set (n = 170), which was used to develop linear regression models containing the polygenic score and 2-SNP interactions. The best-fitting models were tested for replication in 2 independent test sets of cases: (1) 170 individuals with schizophrenia or schizoaffective disorder and (2) 84 patients with broad psychosis (including bipolar disorder, major depressive disorder, and other psychosis). MAIN OUTCOMES AND MEASURES Participants completed a neuropsychological assessment battery designed to target the cognitive deficits of schizophrenia including general cognitive function, episodic memory, working memory, attentional control, and social cognition. RESULTS Higher polygenic scores were associated with poorer performance among patients on IQ, memory, and social cognition, explaining 1% to 3% of variation on these scores (range, P = .01 to .03). Using a narrow psychosis training set and independent test sets of narrow phenotype psychosis (schizophrenia and schizoaffective disorder), broad psychosis, and control participants (n = 89), the addition of 2 interaction terms containing 2 SNPs each increased the R2 for spatial working memory strategy in the independent psychosis test sets from 1.2% using the polygenic score only to 4.8% (P = .11 and .001, respectively) but did not explain additional variation in control participants. CONCLUSIONS AND RELEVANCE These data support a role for the ZNF804A pathway in IQ, memory, and social cognition in cases. Furthermore, we showed that epistasis increases the variation explained above the contribution of the polygenic score.
    JAMA Psychiatry 05/2014; DOI:10.1001/jamapsychiatry.2014.528 · 12.01 Impact Factor
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    ABSTRACT: Background Psychiatric disorders run in families, and early twin, family and adoption studies confirmed that this was due in part to shared genetic inheritance. While candidate gene studies largely failed to reliably identify genetic variants associated with psychiatric disorders, genome-wide association studies are beginning to do so. However, the proportion of phenotypic variance explained remains well below what would be expected from previous heritability estimates.ScopeWe review possible reasons for this ‘missing heritability’, and whether incorporating gene by environment interactions into our models will substantially improve our understanding of the aetiology of psychiatric disorders, and inform clinical perceptions and practice.FindingsWe discuss potential limitations of the gene by environment interaction approach. In particular, we discuss whether these are likely to be a major contributor to psychiatric disorders at the level of the specific interaction (as opposed to at an aggregate level).Conclusions Gene by environment interaction studies offered initial promise that a far greater proportion of phenotypic variance could be explained by incorporating measures of environmental exposures into genetic studies. However, in our opinion, there are few (if any) clear examples of gene by environment interactions in psychiatry, and their scope for informing either our understanding of disease pathology or clinical practice remains limited at present.
    Journal of Child Psychology and Psychiatry 05/2014; 55(10). DOI:10.1111/jcpp.12261 · 5.67 Impact Factor
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    ABSTRACT: Background. Schizophrenia has a neurodevelopmental component to its origin, and may share overlapping pathogenic mechanisms with childhood neurodevelopmental disorders (NDs). Nevertheless, longitudinal studies of psychotic outcomes among individuals with NDs are limited. We report a population-based prospective study of six common childhood NDs, subsequent neurocognitive performance and the risk of psychotic experiences (PEs) in early adolescence. Method. PEs were assessed by semi-structured interviews at age 13 years. IQ and working memory were measured between ages 9 and 11 years. The presence of six NDs (autism spectrum, dyslexia, dyspraxia, dysgraphia, dysorthographia, dyscalculia) was determined from parent-completed questionnaires at age 9 years. Linear regression calculated the mean difference in cognitive scores between children with and without NDs. Associations between NDs and PEs were expressed as odds ratios (ORs) with 95% confidence intervals (CIs); effects of cognitive deficits were examined. Potential confounders included age, gender, father's social class, ethnicity and maternal education. Results. Out of 8220 children, 487 (5.9%) were reported to have NDs at age 9 years. Children with, compared with those without, NDs performed worse on all cognitive measures; the adjusted mean difference in total IQ was 6.84 (95% CI 5.00-8.69). The association between total IQ and NDs was linear (p<0.0001). The risk of PEs was higher in those with, compared with those without, NDs; the adjusted OR for definite PEs was 1.76 (95% CI 1.11-2.79). IQ (but not working memory) deficit partly explained this association. Conclusions. Higher risk of PEs in early adolescence among individuals with childhood ND is consistent with the neurodevelopmental hypothesis of schizophrenia.
    Schizophrenia Research 04/2014; 44(15):1-10. DOI:10.1017/S0033291714000750 · 4.43 Impact Factor
  • Schizophrenia Research 04/2014; 153(S338–S339). DOI:10.1016/S0920-9964(14)70956-9 · 4.43 Impact Factor
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    ABSTRACT: Background. A clearer understanding of the basis for the association between cannabis use and psychotic experiences (PEs) is required. Our aim was to examine the extent to which associations between cannabis and cigarette use and PEs are due to confounding. Method. A cohort study of 1756 adolescents with data on cannabis use, cigarette use and PEs. Results. Cannabis use and cigarette use at age 16 were both associated, to a similar degree, with PEs at age 18 [odds ratio (OR) 1.48, 95% confidence interval (CI) 1.18–1.86 for cannabis and OR 1.61, 95% CI 1.31–1.98 for cigarettes]. Adjustment for cigarette smoking frequency (OR 1.27, 95% CI 0.91–1.76) or other illicit drug use (OR 1.25, 95% CI 0.91–1.73) substantially attenuated the relationship between cannabis and PEs. The attenuation was to a lesser degree when cannabis use was adjusted for in the cigarette PE association (OR 1.42, 95% CI 1.05–1.92). However, almost all of the participants used cannabis with tobacco, including those who classed themselves as non-cigarette smokers. Conclusions. Teasing out the effects of cannabis from tobacco is highly complex and may not have been dealt with adequately in studies to date, including this one. Complementary methods are required to robustly examine the independent effects of cannabis, tobacco and other illicit drugs on PEs.
    Psychological Medicine 04/2014; 44(16):1-10. DOI:10.1017/S0033291714000531 · 5.43 Impact Factor

Publication Stats

5k Citations
992.34 Total Impact Points

Institutions

  • 2006–2014
    • University of Bristol
      • School of Social and Community Medicine
      Bristol, England, United Kingdom
  • 2004–2014
    • University of South Wales
      Понтиприте, Wales, United Kingdom
  • 2002–2014
    • Cardiff University
      • • Department of Psychological Medicine and Neurology
      • • MRC Centre for Neuropsychiatric Genetics & Genomics
      Cardiff, Wales, United Kingdom
  • 2009
    • The University of Warwick
      • Warwick Medical School (WMS)
      Warwick, ENG, United Kingdom
  • 2008
    • University of Washington Seattle
      Seattle, Washington, United States
    • University of Nottingham
      • Division of Psychiatry and Applied Psychology
      Nottigham, England, United Kingdom
  • 2000–2008
    • University of Wales
      • College of Medicine
      Cardiff, Wales, United Kingdom
  • 2003
    • University of Gothenburg
      • Unit of Social Medicine
      Goeteborg, Västra Götaland, Sweden