OBJECTIVE: Neurodevelopmental impairments have been associated with early-onset schizophrenia, early-onset bipolar disorder, and childhood-onset affective disorder. The authors investigated whether delayed childhood motor skills predicted persistent anxiety in adolescence among 6,850 subjects from a national 1958 U.K. birth cohort. METHOD: This historic cohort study used data from the National Child Development Study that was collected when its subjects were 7, 11, and 16 years old. RESULTS: Boys with poor motor skills had more than threefold the odds of maternally rated anxiety at the ages of 11 and 16, but no effect was observed for girls. CONCLUSIONS: Childhood motor impairment was strongly associated with persistent anxiety among male, but not among female, adolescents. The effect modification by sex was greater than expected, as was the effect size for boys. Both findings warrant replication and further examination.
Comment In: Evid Based Ment Health. 2003 Feb;6(1):1812588824
Pregnancy burdens maternal folate reserves. Postpartum restoration to normal folate values may take up to 1 year. Maternal folate deficiency during early pregnancy has been hypothesized as a cause of schizophrenia in the offspring. We investigated whether the risk of schizophrenia is increased in persons conceived shortly after another birth. A population-based cohort was established of 1.43 million persons born in Denmark between 1950 and 1983, yielding 17.6 million person-years of follow-up. Schizophrenia in cohort members (5095 cases) and their siblings and parents was identified by linkage with the Danish Psychiatric Case Register. Relative risks of schizophrenia were estimated by use of log-linear Poisson regression. As compared to intervals of 45 months and longer, the schizophrenia risk ratio was 1.14 (95% confidence interval [CI], 0.97 to 1.35) for interbirth intervals of up to 15 months, 1.32 (95% CI, 1.12 to 1.56) for intervals of 15 to 17 months, 1.38 (95% CI, 1.18 to 1.61), for intervals of 18 to 20 months and 1.13 (95% CI, 1.00 to 1.29) for intervals of 21 to 26 months. Relative risks did not essentially change after adjustment for age, sex, calendar year of diagnosis, maternal and paternal age, history of mental illness in a parent or sibling, sibship size, place of birth, and distance to younger sibling. These results show an association between short birth intervals and schizophrenia in the offspring. Although maternal folate depletion may play a role in this association, we cannot rule out other explanations such as maternal stress during pregnancy and childhood infections.
Psychotic experiences (PE) in individuals of the general population are hypothesized to mark the early expression of the pathology underlying psychosis. This notion of PE as an intermediate phenotype is based on the premise that PE share genetic liability with psychosis. We examined whether PE in childhood was predicted by a family history of mental disorder with psychosis rather than a family history of nonpsychotic mental disorder and whether this association differed by severity of PE. The study examined data on 1632 children from a general population birth cohort assessed at age 11-12 years by use of a semistructured interview covering 22 psychotic symptoms. The Danish national registers were linked to describe the complete family history of hospital-based psychiatric diagnoses. Uni- and multivariable logistic regressions were used to test whether a family history of any mental disorder with psychosis, or of nonpsychotic mental disorder, vs no diagnoses was associated with increased risk of PE in offspring (hierarchical exposure variable). The occurrence of PE in offspring was significantly associated with a history of psychosis among the first-degree relatives (adjusted relative risk [RR] = 3.29, 95% CI: 1.82-5.93). The risk increased for combined hallucinations and delusions (adjusted RR = 5.90, 95% CI: 2.64-13.16). A history of nonpsychotic mental disorders in first-degree relatives did not contribute to the risk of PE in offspring nor did any mental disorder among second-degree relatives. Our findings support the notion of PE as a vulnerability marker of transdiagnostic psychosis. The effect of psychosis in first-degree relatives may operate through shared genetic and environmental factors.
Cites: Nat Genet. 2013 Sep;45(9):984-9423933821
Cites: Ugeskr Laeger. 2013 May 13;175(20):139923663392
OBJECTIVE: This study replicated a previous report that there may be substantial synergism between urbanicity (a proxy environmental risk factor) and familial clustering of psychotic disorder (a proxy genetic risk factor). METHOD: The amount of synergism was estimated from the additive statistical interaction between urbanicity of place of birth and family history of schizophrenia or family history of any severe mental disorder in a population-based Danish cohort of 1,020,063 individuals. RESULTS: There was significant interaction between urbanicity and family history; between 20% and 35% of individuals who had been exposed to both of these risk factors had schizophrenia possibly because of their synergistic effects. CONCLUSIONS: The results suggest that a substantial proportion of the population morbidity force of schizophrenia may be the result of gene-environment interactions associated with urbanicity.
A recently published study of national data by McGrath et al in 2014 showed increased risk of schizophrenia (SCZ) in offspring associated with both early and delayed parental age, consistent with a U-shaped relationship. However, it remains unclear if the risk to the child is due to psychosocial factors associated with parental age or if those at higher risk for SCZ tend to have children at an earlier or later age.
To determine if there is a genetic association between SCZ and age at first birth (AFB) using genetically informative but independently ascertained data sets.
This investigation used multiple independent genome-wide association study data sets. The SCZ sample comprised 18?957 SCZ cases and 22?673 controls in a genome-wide association study from the second phase of the Psychiatric Genomics Consortium, and the AFB sample comprised 12?247 genotyped women measured for AFB from the following 4 community cohorts: Estonia (Estonian Genome Center Biobank, University of Tartu), the Netherlands (LifeLines Cohort Study), Sweden (Swedish Twin Registry), and the United Kingdom (TwinsUK). Schizophrenia genetic risk for each woman in the AFB community sample was estimated using genetic effects inferred from the SCZ genome-wide association study.
We tested if SCZ genetic risk was a significant predictor of response variables based on published polynomial functions that described the relationship between maternal age and SCZ risk in offspring in Denmark. We substituted AFB for maternal age in these functions, one of which was corrected for the age of the father, and found that the fit was superior for the model without adjustment for the father's age.
We observed a U-shaped relationship between SCZ risk and AFB in the community cohorts, consistent with the previously reported relationship between SCZ risk in offspring and maternal age when not adjusted for the age of the father. We confirmed that SCZ risk profile scores significantly predicted the response variables (coefficient of determination R2?=?1.1E-03, P?=?4.1E-04), reflecting the published relationship between maternal age and SCZ risk in offspring by McGrath et al in 2014.
This study provides evidence for a significant overlap between genetic factors associated with risk of SCZ and genetic factors associated with AFB. It has been reported that SCZ risk associated with increased maternal age is explained by the age of the father and that de novo mutations that occur more frequently in the germline of older men are the underlying causal mechanism. This explanation may need to be revised if, as suggested herein and if replicated in future studies, there is also increased genetic risk of SCZ in older mothers.
1] Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.  Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. .
Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.
ECEVE, UMRS 1123, Université Paris Diderot, Sorbonne Paris Cité, INSERM, Paris, France; AP-HP, URC-Eco, DHU Pepsy, F-75004 Paris, France; Foundation FondaMental, French National Science Foundation, Créteil, France. Electronic address: firstname.lastname@example.org.
As part of the Roamer project, we aimed at revealing the share of health research budgets dedicated to mental health, as well as on the amounts allocated to such research for four European countries. Finland, France, Spain and the United Kingdom national public and non-profit funding allocated to mental health research in 2011 were investigated using, when possible, bottom-up approaches. Specifics of the data collection varied from country to country. The total amount of public and private not for profit mental health research funding for Finland, France, Spain and the UK was €10·2, €84·8, €16·8, and €127·6 million, respectively. Charities accounted for a quarter of the funding in the UK and less than six per cent elsewhere. The share of health research dedicated to mental health ranged from 4·0% in the UK to 9·7% in Finland. When compared to the DALY attributable to mental disorders, Spain, France, Finland, and the UK invested respectively €12·5, €31·2, €39·5, and €48·7 per DALY. Among these European countries, there is an important gap between the level of mental health research funding and the economic and epidemiologic burden of mental disorders.
Knowledge on the significance of childhood psychotic symptoms and experiences (PE) is still limited. This study aimed to investigate the prevalence and clinical significance of PE in preadolescent children from the general population by use of in-depth psychopathological interviews and comprehensive diagnostic assessments.
We investigated 1,632 children from the general population-based Copenhagen Child Cohort 2000. PE were measured by semistructured interviews using the K-SADS-PL-items on psychotic and affective symptoms, each symptom scored as not present versus likely or definitely present. The Development and Well-Being Assessment (DAWBA) was used independently to diagnose DSM-IV-mental disorders. Puberty development and sleep disturbance were self-reported. The associations between PE (any lifetime hallucination and/or delusion) and various mental problems and disorders were examined by multivariable binomial regression analyses, adjusting for gender and onset of puberty.
The weighted life time prevalence of PE at age 11-12 years was 10.9% (CI 9.1-12.7). The majority of children with PE (n = 172) either had a diagnosable DSM-IV-mental disorder (31.4%) or self-reported mental health difficulties in absence of a diagnosis (31.4%). The risk of delusions increased with onset of puberty. The risk of PE increased with emotional and neurodevelopmental disorders, subthreshold depressive symptoms, sleep problems and lack of sleep, regardless of whether PE were expressed as hallucinations and/or delusions. The highest correlations were seen for emotional and multiple disorders.
Psychotic experiences are particularly prevalent in the context of affective dysregulation and sleep disturbance, increase with onset of puberty and represent a trans-diagnostic marker of psychopathology.