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Blood-Based Protein Changes in Childhood Are Associated With Increased Risk for Later Psychotic Disorder: Evidence From a Nested Case-Control Study of the ALSPAC Longitudinal Birth Cohort.

ABSTRACT: The identification of early biological changes associated with the psychotic disorder (PD) is important as it may provide clues to the underlying pathophysiological mechanisms. We undertook the first proteomic profiling of blood plasma samples of children who later develop a PD. Participants were recruited from the UK Avon Longitudinal Study of Parents and Children (ALSPAC) cohort who also participated in psychiatric assessment interviews at age 18. Protein expression levels at age 11 were compared between individuals who developed PD at age 18 (n = 37) with population-based age-matched controls (n = 38). Sixty out of 181 plasma proteins profiled were found to be differentially expressed (P < .05) in children with an outcome of the PD. Thirty-four of these proteins were found to be differentially expressed following correction for multiple comparisons. Pathway analysis implicated the complement and coagulation cascade. A second, targeted proteomic approach was used to verify these findings in age 11 plasma from subjects who reported psychotic experiences at age 18 (n = 40) in comparison to age-matched controls (n = 66). Our findings indicate that the complement and coagulation system is dysregulated in the blood during childhood before the development of the PD.

SUBMITTER: English JA

PROVIDER: S-EPMC5814944 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Blood-Based Protein Changes in Childhood Are Associated With Increased Risk for Later Psychotic Disorder: Evidence From a Nested Case-Control Study of the ALSPAC Longitudinal Birth Cohort.

English Jane A JA Lopez Lorna M LM O'Gorman Aoife A Föcking Melanie M Hryniewiecka Magdalena M Scaife Caitriona C Sabherwal Sophie S Wynne Kieran K Dicker Patrick P Rutten Bart P F BPF Lewis Glynn G Zammit Stanley S Cannon Mary M Cagney Gerard G Cotter David R DR

Schizophrenia bulletin 20180201 2

The identification of early biological changes associated with the psychotic disorder (PD) is important as it may provide clues to the underlying pathophysiological mechanisms. We undertook the first proteomic profiling of blood plasma samples of children who later develop a PD. Participants were recruited from the UK Avon Longitudinal Study of Parents and Children (ALSPAC) cohort who also participated in psychiatric assessment interviews at age 18. Protein expression levels at age 11 were compa ...[more]

PMID: 29036721

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Project description:Eviction affects a substantial share of U.S. children, but its effects on child health are largely unknown. Our objectives were to examine how eviction relates to 1) children's health and sociodemographic characteristics at birth, 2) neighborhood poverty and food security at age 5, and 3) obesity in later childhood and adolescence. We analyzed data from the Fragile Families and Child Wellbeing Study, a longitudinal cohort of children born in 20 large U.S. cities. Children who lived in rental housing with known eviction histories and measured outcomes were included. We compared maternal and infant health and sociodemographic characteristics at the time of the child's birth. We then characterized the associations between eviction and neighborhood poverty and food security at age 5 and obesity at ages 5, 9, and 15 using log binomial regression with inverse probability of treatment and censoring weights. Of the 2556 children included in objective 1, 164 (6%) experienced eviction before age 5. Children who experienced eviction had lower household income and maternal education and were more likely to be born to mothers who were unmarried, smoked during pregnancy, and had mental health problems. Evicted and non-evicted children were equally likely to experience high neighborhood poverty at age 5 (prevalence ratio (PR) = 1.03, 95% CI 0.82, 1.29) but had an increased prevalence of low food security (PR = 2.16, 95% CI 1.46, 3.19). Obesity prevalence did not differ at age 5 (PR = 1.01; 95% CI 0.58, 1.75), 9 (PR = 1.08; 95% CI 0.715, 1.55); or 15 (PR = 1.05; 95% CI 0.51, 2.18). In conclusion, children who went on to experience eviction showed signs of poor health and socioeconomic disadvantage already at birth. Eviction in early childhood was not associated with children's likelihood of neighborhood poverty, suggesting that eviction may not qualitatively change children's neighborhood conditions in this disadvantaged sample. Though we saw evidence supporting an association with low child food security at age 5, we did not find eviction to be associated with obesity in later childhood and adolescence.

Project description:BackgroundThe alterations in cortical morphology, such as cortical thinning, observed in psychotic disorder, may be the outcome of interacting genetic and environmental effects. It has been suggested that urban upbringing may represent a proxy environmental effect impacting cortical thickness (CT). Therefore, the current study examined whether the association between group as a proxy genetic variable (patients with psychotic disorder [high genetic risk], healthy siblings of patients [intermediate risk] and healthy control subjects [average risk]) and CT was conditional on different levels of the childhood urban environment and whether this was sex-dependent.MethodsT1-weighted MRI scans were acquired from 89 patients with a psychotic disorder, 95 non-psychotic siblings of patients with psychotic disorder and 87 healthy control subjects. Freesurfer software was used to measure CT. Developmental urban exposure was classified as low, medium, and high, reflecting the population density and the number of moves between birth and the 15th birthday, using data from the Dutch Central Bureau of Statistics and the equivalent database in Belgium. Multilevel regression analyses were used to examine the association between group, sex, and urban upbringing (as well as their interactions) and cortical CT as the dependent variable.ResultsCT was significantly smaller in the patient group compared to the controls (B = -0.043, p <0.001), but not in the siblings compared to the controls (B = -0.013, p = 0.31). There was no main effect of developmental urbanicity on CT (B = 0.001, p = 0.91). Neither the three-way group × urbanicity × sex interaction (?2 = 3.73, p = 0.16), nor the two-way group × urbanicity interaction was significant (?2 = 0.51, p = 0.77).ConclusionThe negative association between (familial risk for) psychotic disorder and CT was not moderated by developmental urbanicity, suggesting that reduced CT is not the outcome of familial sensitivity to the proxy environmental factor 'urban upbringing'.

Dataset Information

Blood-Based Protein Changes in Childhood Are Associated With Increased Risk for Later Psychotic Disorder: Evidence From a Nested Case-Control Study of the ALSPAC Longitudinal Birth Cohort.

Publications

Blood-Based Protein Changes in Childhood Are Associated With Increased Risk for Later Psychotic Disorder: Evidence From a Nested Case-Control Study of the ALSPAC Longitudinal Birth Cohort.

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