[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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; · 5.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Schizophrenia Research 07/2014; · 4.59 Impact Factor
[Show abstract][Hide abstract] 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; · 5.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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; · 5.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Psychotic experiences are not uncommon in general population samples, but no studies have examined to what extent confirmed risk variants for schizophrenia are associated with such experiences. A total of 3483 children in a birth cohort study participated in semistructured interviews for psychotic experiences at ages 12 and 18. We examined whether (1) a composite measure of risk for schizophrenia conferred by common alleles (polygenic score) was associated with psychotic experiences, (2) variants with genome-wide evidence for association with schizophrenia were associated with psychotic experiences, and (3) we could identify genetic variants for psychotic experiences using a genome-wide association (GWA) approach. We found no evidence that a schizophrenia polygenic score, or variants showing genome-wide evidence of association with schizophrenia, were associated with adolescent psychotic experiences within the general population. In fact, individuals who had a higher number of risk alleles for genome-wide hits for schizophrenia showed a decreased risk of psychotic experiences. In the GWA study, no variants showed GWA for psychotic experiences, and there was no evidence that the strongest hits (P < 5 × 10(-5)) were enriched for variants associated with schizophrenia in large consortia. Although polygenic scores are weak tools for prediction of schizophrenia, they show strong evidence of association with this disorder. Our findings, however, lend little support to the hypothesis that psychotic experiences in population-based samples of adolescents share a comparable genetic architecture to schizophrenia, or that utilizing a broader and more common phenotype of psychotic experiences will be an efficient approach to increase understanding of the genetic etiology of schizophrenia.
[Show abstract][Hide abstract] ABSTRACT: Children with 22q11.2 deletion syndrome (22q11.2DS) have been reported to have high rates of cognitive and psychiatric problems.
To establish the nature and prevalence of psychiatric disorder and neurocognitive impairment in children with 22q11.2DS and test whether risk of psychopathology is mediated by the children's intellectual impairment.
Neurocognition and psychopathology were assessed in 80 children with 22q11.2DS (mean age 10.2 years, s.d. = 2.1) and 39 sibling controls (mean age 10.9 years, s.d. = 2.0).
More than half (54%) of children with 22q11.2DS met diagnostic criteria for one or more DSM-IV-TR psychiatric disorder. These children had lower IQ (mean 76.8, s.d. = 13.0) than controls (mean 108.6, s.d. = 15.2) (P<0.001) and showed a range of neurocognitive impairments. Increased risk of psychopathology was not mediated by intellectual impairment.
22q11.2DS is not related to a specific psychiatric phenotype in children. Moreover, the deletion has largely independent effects on IQ and risk of psychopathology, indicating that psychopathology in 22q11.2DS is not a non-specific consequence of generalised cognitive impairment.
The British journal of psychiatry: the journal of mental science 10/2013; · 6.62 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The risk of childhood behavioural and psychiatric diseases could be substantially reduced if modifiable risk factors for these disorders were identified. The critical period for many of these exposures is likely to be in utero as this is the time when brain development is most rapid. However, due to confounding and other limitations of traditional epidemiological studies, identification of causal risk factors has proved challenging and on the whole research in this area has not been fruitful.
In this review, we highlight several alternative approaches including; comparisons across settings, the use of negative controls and natural experiments, which includes migration studies, studies of individuals conceived using in vitro fertilisation and not least Mendelian randomisation. We have illustrated these approaches using examples of behavioural and psychiatric disorders.
By having these approaches outlined together in one review, researchers can consider which of these methods would be most suitable for their study question. We have particularly focussed on Mendelian randomisation, as this is a relatively novel concept, in doing so, we have illustrated the concept and discused the implementation and the limitations of this approach.
Journal of Child Psychology and Psychiatry 10/2013; 54(10):1095-108. · 5.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Psychotic symptoms are common in adolescents in the general population but it is unknown whether they are associated with poor social functioning.
To investigate whether adolescent psychotic symptoms are associated with poor social functioning measured by peer relationships.
Data from the Avon Longitudinal Study of Parents and Children cohort was used. Logistic regression was used to explore the relationship between psychotic symptoms at 12.9years detected using a semi-structured interview and poor social functioning at 13.2years using parent-reported peer problems from the Strengths and Difficulties Questionnaire.
There was strong evidence (p<0.001) of an unadjusted association between psychotic symptoms and poor social functioning (OR 1.41, 95% CI 1.24-1.61). The association was attenuated after adjusting for earlier social functioning, socio-demographic variables, bullying status and IQ (OR 1.28, 95% CI 1.09-1.50). The majority of the crude association was explained by additional adjustment for emotional problems including depression at age 12, emotional symptoms, hyperactivity and conduct problems at age 11 (OR 1.07, 95% CI 0.89-1.29).
Adolescents with psychotic symptoms may be no more likely to have poor social functioning than other adolescents, once other emotional problems have been taken into account. The discussion addressed two explanations. First, emotional problems may be on the causal pathway from psychotic symptoms to poor social functioning. Alternatively, emotional symptoms may act as a confounder, suggesting that medical intervention may be inappropriate. It is the impact of psychotic symptoms on the individual that should dictate whether any intervention is required.
Schizophrenia Research 09/2013; · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17–29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn’s disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
[Show abstract][Hide abstract] 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 07/2013; · 4.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Low early life vitamin D status is associated with an increased risk of schizophrenia and psychotic experiences. Here we examine if maternal pregnancy vitamin D concentrations are associated with offspring psychotic experiences as young adults. METHODS: A community sample of 2047 participants was investigated. Maternal prenatal 25 hydroxyvitamin D (25(OH)D) concentrations were assessed with tandem mass spectroscopy. Psychotic experiences were assessed at age 18years using a semi-structured clinical interview. RESULTS: 177 cohort members reported suspected or definite psychotic experiences, There was no evidence of an association between maternal 25(OH)D concentrations as quartiles (p=0.85 hypothesis test of general association versus no association across the quartiles) or as a continuous variable (p=0.89) versus experience of suspected and definite psychotic experiences at 18years. Within the cohort, only 29 subjects met criteria for a psychotic disorder at age 18. Based on this sample, there was no significant association between maternal 25(OH)D and psychotic disorder at 18years. DISCUSSION: Maternal vitamin D levels were not associated with risk of psychotic experiences nor psychotic disorders in this birth cohort.
Schizophrenia Research 06/2013; · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE The authors examined the development of psychotic experiences and psychotic disorders in a large population-based sample of young adults and explored their relationship to psychotic phenomena earlier in childhood. METHOD The authors conducted a longitudinal birth cohort study of individuals assessed with the semistructured Psychosis-Like Symptom Interviews at ages 12 and 18 years. RESULTS Of the 4,724 individuals interviewed at age 18, 433 (9.2%) had either suspected (N=203 [4.3%]) or definite (N=230 [4.9%]) psychotic experiences. Of these, 79 (1.7%) met criteria for a psychotic disorder, and of those, only 50% sought professional help. All psychotic outcomes were more likely in young women and in those from socioeconomically disadvantaged backgrounds. Of the participants who had psychotic experiences at age 12, 78.7% had remitted by age 18. The risk of psychotic disorders at age 18 was greater in those with suspected (odds ratio=5.6, 95% CI=2.6-12.1) and especially in those with definite (odds ratio=12.7, 95% CI=6.2-26.1) psychotic experiences at age 12, and also among those with psychotic experiences at age 12 attributed to sleep or fever or with nonpsychotic experiences such as depersonalization. The positive predictive values for increasing frequency of experiences at age 12 predicting psychotic disorders at age 18 ranged from 5.5% to 22.8%. CONCLUSIONS Despite evidence for a continuum of psychotic experiences from as early as age 12, positive predictive values for predicting psychotic disorders were too low to offer real potential for targeted interventions. Psychotic disorders in young adults are relatively uncommon, but they constitute an important unmet need for care given that half of the individuals in this study who met criteria for a psychiatric disorder had not sought help for these problems despite high levels of associated distress and impairment.
American Journal of Psychiatry 05/2013; · 14.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE Psychotic experiences in children are associated with an elevated risk of developing psychosis. The authors investigated whether the pattern of cognitive deficits present in psychosis also exists in children with psychotic experiences within the general population. METHOD The authors examined the longitudinal relationships between key cognitive domains, selected a priori based on their association with schizophrenia, and onset of psychotic experiences in children from the Avon Longitudinal Study of Parents and Children and whether these associations were independent of one another. RESULTS Lower performance in the domains of processing speed at age 8 years (odds ratio=1.24, 95% CI=1.12-1.36) and attention at age 11 (odds ratio=1.14, 95% CI=1.04-1.25) and decline of processing speed between the ages of 8 and 11 (odds ratio=1.29, 95% CI=1.15-1.45) were associated with higher risk of psychotic experiences at age 12. When adjusting for the other cognitive domains, processing speed at age 8 (odds ratio=1.20, 95% CI=1.09-1.33) was the measure most strongly associated with psychotic experiences. CONCLUSIONS Defective processing speed is a particularly strong predictor of psychotic experiences in children. Furthermore, the pattern of associations between cognition and psychotic experiences in children within the general population is similar to the one between cognition and schizophrenia. These findings have potentially important implications for understanding the pathogenesis of psychotic disorders and the specific deficits that seem to place children at higher risk of psychopathology.
American Journal of Psychiatry 05/2013; 170(5):550-7. · 14.72 Impact Factor