Association of Genetic Risk for Schizophrenia and Bipolar Disorder With Infant Neuromotor Development

Serdarević, Fadila; Jansen, Philip R.; Ghassabian, Akhgar; White, Tonya; Jaddoe, Vincent W. V.; Posthuma, Daniëlle; Tiemeier, Henning

doi:10.1001/jamapsychiatry.2017.3459

Cited by 23 publications

(17 citation statements)

References 7 publications

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“…However, for bipolar disorder risk genes the elevation in foetal expression was less pronounced and we failed to observe any significant evidence of a prenatal bias in gene expression, consistent with the view that these conditions can be collectively viewed as lying on a spectrum of neurodevelopmental risk, with bipolar disorder characterised by a lower prenatal burden of risk 4,34,35 . These results are also consistent with a recent study showing that polygenic risk for schizophrenia, but not polygenic risk for bipolar disorder, is associated with impairments in early infant neuromotor development 43 .…”

Section: Discussionsupporting

confidence: 92%

Dynamic expression of risk genes for schizophrenia and bipolar disorder across development

Clifton

Hannon

Florio

et al. 2018

Preprint

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Common genetic variation contributes a substantial proportion of risk for both schizophrenia and bipolar disorder. Furthermore, there is evidence of significant, but not complete, overlap in genetic risk between schizophrenia and bipolar disorder. It has been hypothesised that genetic variants conferring risk for these disorders do so by influencing brain development, leading to the later emergence of symptoms. The comparative profile of risk gene expression for schizophrenia and bipolar disorder across development over different brain regions however remains unclear. Using genotypes derived from genome wide associations studies of the largest available cohorts of patients and control subjects, we investigated whether genes enriched for schizophrenia and bipolar disorder association show a bias for expression across any of 13 developmental stages in prefrontal cortical and subcortical brain regions. We show that genes associated with schizophrenia have a strong bias towards increased expression in the prefrontal cortex during early midfetal development and early infancy, and decreased expression during late childhood which normalises in adolescence. Riskassociated genes for bipolar disorder shared this postnatal expression profile but did not exhibit a bias towards expression at any prenatal stage. These results emphasise the dynamic expression of genes harbouring risk for schizophrenia and bipolar disorder across prefrontal cortex development and support the view that prenatal neurodevelopmental events are more strongly associated with schizophrenia than bipolar disorder.

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Section: Discussionsupporting

confidence: 92%

Dynamic expression of risk genes for schizophrenia and bipolar disorder across development

Clifton

Hannon

Florio

et al. 2018

Preprint

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“…In comparison with links with symptoms, the association of SZ PRS with neurocognitive deficits has been stronger. The SZ PRS has been linked with prodromal motor deficits 7 , as well as cognitive decline and lower educational attainment in the general population 8,9 . However, it is unclear whether SZ PRS predicts either cognition or cognitive decline in people with psychotic disorders 10 .…”

Section: Introductionmentioning

confidence: 99%

Schizophrenia polygenic risk score and 20-year course of illness in psychotic disorders

Jonas

Lencz

et al. 2019

Transl Psychiatry

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Understanding whether and how the schizophrenia polygenic risk score (SZ PRS) predicts course of illness could improve diagnosis and prognostication in psychotic disorders. We tested whether the SZ PRS predicts symptoms, cognition, illness severity, and diagnostic changes over the 20 years following first admission. The Suffolk County Mental Health Project is an inception cohort study of first-admission patients with psychosis. Patients were assessed six times over 20 years, and 249 provided DNA. Geographically- and demographically-matched never psychotic adults were recruited at year 20, and 205 provided DNA. Symptoms were rated using the Schedule for the Assessment of Positive Symptoms and Schedule for the Assessment of Negative Symptoms. Cognition was evaluated with a comprehensive neuropsychological battery. Illness severity and diagnosis were determined by consensus of study psychiatrists. SZ PRS was significantly higher in first-admission than never psychotic groups. Within the psychosis cohort, the SZ PRS predicted more severe negative symptoms (β = 0.21), greater illness severity (β = 0.28), and worse cognition (β = −0.35), across the follow-up. The SZ PRS was the strongest predictor of diagnostic shifts from affective to non-affective psychosis over the 20 years (AUC = 0.62). The SZ PRS predicts persistent differences in cognition and negative symptoms. The SZ PRS also predicts who among those who appear to have a mood disorder with psychosis at first admission will ultimately be diagnosed with a schizophrenia spectrum disorder. These findings show potential for the SZ PRS to become a tool for diagnosis and treatment planning.

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“…Shared genetic liability might partly explain the association between nonoptimal neuromotor development during infancy and autistic traits in childhood. Likewise, the genetic risk score for schizophrenia predicted poor motor development, suggesting that low tonus may be one of the earliest manifestations of schizophrenia risk (Serdarevic et al 2018).…”

Section: Infant Neuromotor Development and Childhood Problem Behaviormentioning

confidence: 99%

Epidemiology of Child Psychopathology

Verhulst¹,

Tiemeier²

2020

Mental Health and Illness Worldwide

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Background: Child psychiatric epidemiology has developed rapidly from descriptive, cross-sectional studies in the 1960s to the current large-scale prospective cohorts that unravel etiological mechanisms. Objectives: To give an overview of epidemiological studies that have influenced child psychiatry. Methods: A chronological overview of selected major milestone studies to demonstrate the development of child psychiatric epidemiology, with a more in-depth discussion of findings and methodological issues exemplified in one cohort, the Generation R Study

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Association of Genetic Risk for Schizophrenia and Bipolar Disorder With Infant Neuromotor Development

Cited by 23 publications

References 7 publications

Dynamic expression of risk genes for schizophrenia and bipolar disorder across development

Dynamic expression of risk genes for schizophrenia and bipolar disorder across development

Schizophrenia polygenic risk score and 20-year course of illness in psychotic disorders

Epidemiology of Child Psychopathology

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