[Show abstract][Hide abstract] ABSTRACT: Depression is common, especially in women of child-bearing age; prevalence estimates for this group range from 8% to 12%, and there is robust evidence that maternal depression is associated with mental health problems in offspring. Suicidal behaviour is a growing concern amongst young people and those exposed to maternal depression are likely to be especially at high risk. The aim of this study was to utilise a large, prospective population cohort to examine the relationship between depression symptom trajectories in mothers over the first eleven years of their child's life and subsequent adolescent suicidal ideation. An additional aim was to test if associations were explained by maternal suicide attempt and offspring depressive disorder. Data were utilised from a population-based birth cohort: the Avon Longitudinal Study of Parents and Children. Maternal depression symptoms were assessed repeatedly from pregnancy to child age 11 years. Offspring suicidal ideation was assessed at age 16 years. Using multiple imputation, data for 10,559 families were analysed. Using latent class growth analysis, five distinct classes of maternal depression symptoms were identified (minimal, mild, increasing, sub-threshold, chronic-severe). The prevalence of past-year suicidal ideation at age 16 years was 15% (95% CI: 14-17%). Compared to offspring of mothers with minimal symptoms, the greatest risk of suicidal ideation was found for offspring of mothers with chronic-severe symptoms [OR 3.04 (95% CI 2.19, 4.21)], with evidence for smaller increases in risk of suicidal ideation in offspring of mothers with sub-threshold, increasing and mild symptoms. These associations were not fully accounted for by maternal suicide attempt or offspring depression diagnosis. Twenty-six percent of non-depressed offspring of mothers with chronic-severe depression symptoms reported suicidal ideation. Risk for suicidal ideation should be considered in young people whose mothers have a history of sustained high levels of depression symptoms, even when the offspring themselves do not have a depression diagnosis.
PLoS ONE 07/2015; 10(7):e0131885. DOI:10.1371/journal.pone.0131885 · 3.23 Impact Factor
[Show abstract][Hide abstract] 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; 50(7). DOI:10.1007/s00127-015-1072-8 · 2.58 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: Converging evidence implicates immune abnormalities in schizophrenia (SCZ), and recent genome-wide association studies (GWAS) have identified immune-related single-nucleotide polymorphisms (SNPs) associated with SCZ. Using the conditional false discovery rate (FDR) approach, we evaluated pleiotropy in SNPs associated with SCZ (n=21 856) and multiple sclerosis (MS) (n=43 879), an inflammatory, demyelinating disease of the central nervous system. Because SCZ and bipolar disorder (BD) show substantial clinical and genetic overlap, we also investigated pleiotropy between BD (n=16 731) and MS. We found significant genetic overlap between SCZ and MS and identified 21 independent loci associated with SCZ, conditioned on association with MS. This enrichment was driven by the major histocompatibility complex (MHC). Importantly, we detected the involvement of the same human leukocyte antigen (HLA) alleles in both SCZ and MS, but with an opposite directionality of effect of associated HLA alleles (that is, MS risk alleles were associated with decreased SCZ risk). In contrast, we found no genetic overlap between BD and MS. Considered together, our findings demonstrate genetic pleiotropy between SCZ and MS and suggest that the MHC signals may differentiate SCZ from BD susceptibility.
[Show abstract][Hide abstract] 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
[Show abstract][Hide abstract] 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
[Show abstract][Hide abstract] ABSTRACT: Background
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.
The present investigation was a cohort study of 50 087 Swedish men with data on cannabis use at the ages of 18–20 years. A total of 357 cases of schizophrenia were identified from in-patient care and followed up from 1973 to 2007.
Schizophrenia patients with a history of cannabis use had a higher median duration of first hospital episode (59 days v. 30 days). Patients with a history of cannabis use had a higher median rate of readmission (10 times v. four times). Also, total number of hospital days was higher in patients with a history of cannabis use compared with those without (547 days v. 184 days). Patients with a history of cannabis use had an increased odds of having more than 20 hospital readmissions compared with non-users [3.1, 95% confidence interval (CI) 1.3–7.3] as well as an increased odds of hospital admission lasting more than 2 years (2.4, 95% CI 1.1–7.4) after controlling for diagnosis of personality disorders, family socio-economic position, IQ score, civil status, place of residence, risky use of alcohol and use of other drugs. Patients with a history of cannabis use were less likely to have paranoid schizophrenia compared with never users (8% v. 17%) in the first admission.
Schizophrenia patients with a history of cannabis use had a significantly higher burden of lifetime in-patient care than non-cannabis users. Not only does cannabis increase the risk of schizophrenia, but also our findings indicate that the course and prognosis of schizophrenia may be more severe than schizophrenia cases in general.
Psychological Medicine 09/2014; 44(12):2513-2521. DOI:10.1017/S0033291714000191 · 5.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
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.
We used data from 7030 subjects from a birth cohort study. Depression and PEs at age 18
years were assessed using self-report questionnaires and semi-structured interviews. We
compared the extent to which risk factors for schizophrenia across sociodemographic,
familial, neurodevelopmental, stress–adversity, emotional–behavioural and substance use
domains showed different associations with PEs and depression within bivariate models
that allowed for their correlation.
Most of the exposures examined were associated, to a similar degree, with an increased
risk of both outcomes. However, whereas female sex and family history of depression
showed some discrimination as potential risk factors for depression and PEs, with
stronger associations in the former, markers of abnormal neurodevelopment showed
stronger associations with PEs.
The argument that PEs are valid markers for studying the aetiology of schizophrenia,
made simply on the basis that they share risk factors in common, is not well supported.
PEs seem to be a weak index of genetic and environmental risk for schizophrenia;
however, studies disentangling aetiological pathways to PEs from those impacting upon
co-morbid psychopathology might provide important insights into the aetiology of
Psychological Medicine 09/2014; 44(12):2557-2566. DOI:10.1017/S0033291714000026 · 5.43 Impact Factor
[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; 55(10). DOI:10.1111/jcpp.12308 · 5.67 Impact Factor
[Show abstract][Hide abstract] 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