Stanley Zammit

University of Bristol, Bristol, England, United Kingdom

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Publications (116)937.66 Total impact

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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.
    Journal of the American Academy of Child & Adolescent Psychiatry 02/2015; 47. 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: 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; 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 · 5.42 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 · 5.42 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
  • Schizophrenia Research 04/2014; 153:S7-S8. DOI:10.1016/S0920-9964(14)70023-4 · 4.43 Impact Factor
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    ABSTRACT: The Mood and Feelings Questionnaire (MFQ) is widely used for the assessment of depression in adolescents. The main aim of this study was to examine the concurrent and predictive validity of a composite of four MFQ items related to suicidal ideation using an interview measure of suicidal ideation. A prospective 3-wave high-risk study of offspring of parents with recurrent depression was used including 294 families where children were initially aged 9–17 years. Measures included four parent and child rated MFQ items assessing suicide-related ideation (referred to here as the “MFQ-SI”) and a clinically-defined interview measure of suicidal ideation. A parent-child combined MFQ-SI subscale performed well as a screening tool against the interview measure of suicidal ideation (baseline AUC (95% CI):0.92 (0.85–1.00)). Longitudinally, this measure showed reasonable predictive validity against future suicidal ideation (AUC (95% CI):0.73 (0.58–0.88)). Lastly, there was evidence that a child-rated MFQ-SI scale performed better than a parent-rated one in detecting concurrent suicidal ideation. Longitudinally, both parent and child scales showed reasonable predictive validity against future suicidal ideation. In summary, a brief screen using four MFQ items related to suicidal ideation performs well in identifying concurrent and future suicidal ideation in high-risk adolescents.
    04/2014; DOI:10.1016/j.psychres.2014.01.040
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    ABSTRACT: To examine associations between specific parasomnias and psychotic experiences in childhood. Birth cohort study. Information on the presence of frequent nightmares in children was obtained prospectively from mothers during multiple assessments conducted when children were aged between 2.5 and 9 y. Children were interviewed at age 12 y about nightmares, night terrors, sleepwalking, and psychotic experiences (delusions, hallucinations, and thought interference) occurring in the previous 6 mo. Assessments were completed in participants' homes or a University clinic within the UK. There were 6,796 children (3,462 girls, 50.9%) who completed the psychotic experiences interview. Children who were reported by their mothers as experiencing frequent nightmares between 2.5 and 9 y of age were more likely to report psychotic experiences at age 12 y, regardless of sex, family adversity, emotional or behavioral problems, IQ and potential neurological problems (odds ratio (OR) = 1.16, [95% confidence intervals (CI) = 1.00, 1.35], P = 0.049). Children reporting any of the parasomnias at age 12 y also had higher rates of concurrent psychotic experiences than those without such sleeping problems, when adjusting for all confounders (OR = 3.62 [95% CI = 2.57, 5.11], P < 0.001). Difficulty getting to sleep and night waking were not found to be associated with psychotic experiences at age 12 y when controlling for confounders. Nightmares and night terrors, but not other sleeping problems, in childhood were associated with psychotic experiences at age 12 years. These findings tentatively suggest that arousal and rapid eye movement forms of sleep disorder might be early indicators of susceptibility to psychotic experiences. Fisher HL; Lereya ST; Thompson A; Lewis G; Zammit S; Wolke D. Childhood parasomnias and psychotic experiences at age 12 years in a United Kingdom birth cohort. SLEEP 2014;37(3):475-482.
    Sleep 03/2014; 37(3):475-82. DOI:10.5665/sleep.3478 · 5.06 Impact Factor
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    ABSTRACT: Victims of bullying are at risk for psychotic experiences in early adolescence. It is unclear if this elevated risk extends into late adolescence. The aim of this study was to test whether bullying perpetration and victimization in elementary school predict psychotic experiences in late adolescence. Method The current study is based on the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective community-based study. A total of 4720 subjects with bullying perpetration and victimization were repeatedly assessed between the ages of 8 and 11 years by child and mother reports. Suspected or definite psychotic experiences were assessed with the Psychosis-Like Symptoms semi-structured interview at age 18 years. Controlling for child's gender, intelligence quotient at age 8 years, childhood behavioural and emotional problems, and also depression symptoms and psychotic experiences in early adolescence, victims [child report at 10 years: odds ratio (OR) 2.4, 95% confidence interval (CI) 1.6���3.4; mother report: OR 1.6, 95% CI 1.1���2.3], bully/victims (child report at 10 years: OR 3.1, 95% CI 1.7���5.8; mother: OR 2.9, 95% CI 1.7���5.0) and bullies (child report at 10 years: OR 4.9, 95% CI 1.3���17.7; mother: OR 1.2, 95% CI 0.46���3.1, n.s.) had a higher prevalence of psychotic experiences at age 18 years. Path analysis revealed that the association between peer victimization in childhood and psychotic experiences at age 18 years was only partially mediated by psychotic or depression symptoms in early adolescence. Involvement in bullying, whether as victim, bully/victim or bully, may increase the risk of developing psychotic experiences in adolescence. Health professionals should ask routinely during consultations with children about their bullying of and by peers.
    Psychological Medicine 12/2013; DOI:10.1017/S0033291713002912 · 5.43 Impact Factor
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    ABSTRACT: Depression and anxiety co-occur with substance use and abuse at a high rate. Ascertaining whether substance use plays a causal role in depression and anxiety is difficult or impossible with conventional observational epidemiology. Mendelian randomisation uses genetic variants as a proxy for environmental exposures, such as substance use, which can address problems of reverse causation and residual confounding, providing stronger evidence about causality. Genetic variants can be used instead of directly measuring exposure levels, in order to gain an unbiased estimate of the effect of various exposures on depression and anxiety. The suitability of the genetic variant as a proxy can be ascertained by confirming that there is no relationship between variant and outcome in those who do not use the substance. At present, there are suitable instruments for tobacco use, so we use that as a case study. Proof-of-principle Mendelian randomisation studies using these variants have found evidence for a causal effect of smoking on body mass index. Two studies have investigated tobacco and depression using this method, but neither found strong evidence that smoking causes depression or anxiety; evidence is more consistent with a self-medication hypothesis. Mendelian randomisation represents a technique that can aid understanding of exposures that may or may not be causally related to depression and anxiety. As more suitable instruments emerge (including the use of allelic risk scores rather than individual single nucleotide polymorphisms), the effect of other substances can be investigated. Linkage disequilibrium, pleiotropy, and population stratification, which can distort Mendelian randomisation studies, are also discussed.
    Depression and Anxiety 12/2013; 30(12). DOI:10.1002/da.22150 · 4.29 Impact Factor
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    ABSTRACT: In clinical populations paranoid delusions are associated with making global, stable and external attributions for negative events. Paranoia is common in community samples but it is not known whether it is associated with a similar cognitive style. This study investigates the association between cognitive style and paranoia in a large community sample of young adults. 2694 young adults (mean age 17.8, SD 4.6) from the ALSPAC cohort provided data on psychotic experiences and cognitive style. Psychotic experiences were assessed using a semi-structured interview and cognitive style was assessed using the Cognitive Styles Questionnaire-Short Form (CSQ-SF) on the same occasion. Logistic regression was used to investigate associations between paranoia and CSQ-SF scores, both total and domain-related (global, stable, self, external). The role of concurrent self-reported depressive symptoms in the association was explored. Paranoia was associated with Total CSQ-SF scores (adjusted OR 1.69 95% CI 1.29, 2.22), as well as global (OR 1.56 95% CI 1.17, 2.08), stable (OR 1.56 95% CI 1.17, 2.08) and self (OR 1.37 95% CI 1.05, 1.79) domains, only Total score and global domain associations remained after additional adjustment for self-reported depression. There was no association between paranoia and external cognitive style (OR 1.10 95% CI 0.83, 1.47). Paranoid ideation in a community sample is associated with a global rather than an external cognitive style. An external cognitive style may be a characteristic of more severe paranoid beliefs. Further work is required to determine the role of depression in the association between cognitive style and paranoia.
    PLoS ONE 11/2013; 8(11):e80055. DOI:10.1371/journal.pone.0080055 · 3.53 Impact Factor

Publication Stats

5k Citations
937.66 Total Impact Points

Institutions

  • 2006–2014
    • University of Bristol
      • School of Social and Community Medicine
      Bristol, England, United Kingdom
  • 2002–2014
    • Cardiff University
      • • Department of Psychological Medicine and Neurology
      • • MRC Centre for Neuropsychiatric Genetics & Genomics
      Cardiff, Wales, United Kingdom
  • 2013
    • University of South Wales
      Понтиприте, 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
  • 2000–2008
    • University of Wales
      • College of Medicine
      Cardiff, Wales, United Kingdom
  • 2003
    • University of Gothenburg
      • Unit of Social Medicine
      Goeteborg, Västra Götaland, Sweden