S.16.02 Schizophrenia and the neurodevelopmental continuum; new support from genomics

Owen, M.J.

doi:10.1016/j.euroneuro.2018.11.954

Cited by 32 publications

(47 citation statements)

References 72 publications

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“…Interestingly, most of these syndromic CNVs related to SCZ are also concurrently associated with other brain-related phenotypes, including autism spectrum disorder (ASD), bipolar disorder and intellectual disability (ID)(Chen et al, 2016; Deshpande and Weiss, 2018; Forsingdal et al, 2016; Larson et al, 2018). This is in line with the neurodevelopmental continuum model, wherein SCZ forms part of a spectrum of neurodevelopmental disorders, including ASD, bipolar disorder, ID and attention-deficit/hyperactivity disorder, suggesting common underlying pathogenetic pathways (Davis et al, 2016; Owen and O’Donovan, 2017).…”

Section: Introductionsupporting

confidence: 86%

“…Perhaps not surprisingly, most of the SCZ-related genes seen within the CNVs identified have also been associated with other neuropsychiatric and neurodevelopmental conditions, contributing further evidence to support the neurodevelopmental continuum model (Davis et al, 2016; Owen and O’Donovan, 2017). For example, the RMB8A gene contained within the 1q21.1 microdeletion in patient 15 has been associated with ID and anxiety behaviours (Alachkar et al, 2013; Gamba et al, 2016; Zou et al, 2015), while deletions of NRXN1 , seen in two patients, are strongly associated with neuropsychiatric and neurodevelopmental disorders, including SCZ and ASD (Kirov et al, 2009; Marshall et al, 2017; Rujescu et al, 2008).…”

Section: Discussionmentioning

confidence: 62%

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Copy number variant syndromes are frequent in schizophrenia: progressing towards a CNV-schizophrenia model

Sriretnakumar

Zai

Wasim

et al. 2019

Preprint

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The genetic underpinnings of schizophrenia (SCZ) remain unclear. SCZ genetic studies thus far have only identified numerous single nucleotide polymorphisms with small effect sizes and a handful of copy number variants (CNVs). This study investigates the prevalence of well-characterized CNV syndromes and candidate CNVs within a cohort of 348 SCZ patients, and explores correlations to their phenotypic findings. There was an enrichment of syndromic CNVs in the cohort, as well as brain-related and immune pathway genes within the detected CNVs. SCZ patients with brain-related CNVs had increased CNV burden, neurodevelopmental features, and types of hallucinations. Based on these results, we propose a CNV-SCZ model wherein specific phenotypic profiles should be prioritized for CNV screening within the SCZ patient population.

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Section: Introductionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 62%

Copy number variant syndromes are frequent in schizophrenia: progressing towards a CNV-schizophrenia model

Sriretnakumar

Zai

Wasim

et al. 2019

Preprint

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“…Moreover, studies on intervention in individuals with ultra‐high‐risk states have provided promising results. Evidence also confirms that schizophrenia is a neurodevelopmental disorder with subtle signs long before psychosis onset. These findings suggest that intervention should begin already in the premorbid phase.…”

mentioning

confidence: 87%

Psychopathology in 7‐year‐old children with familial high risk of developing schizophrenia spectrum psychosis or bipolar disorder – The Danish High Risk and Resilience Study ‐ VIA 7, a population‐based cohort study

et al. 2018

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This study aimed to compare the psychopathological profiles of children at familial high risk of schizophrenia spectrum psychosis (FHR-SZ) or bipolar disorder (FHR-BP) with population-based controls. We used Danish nationwide registers to retrieve a cohort of 522 seven-year-old children of parents with schizophrenia spectrum psychosis (N=202), bipolar disorder (N=120) or none of these disorders (N=200). Psychopathology was assessed by reports from multiple informants, including children, parents and teachers. Lifetime DSM-IV diagnoses were ascertained by blinded raters through the Schedule for Affective Disorders and Schizophrenia for School-Age Children. The dimensional assessment of psychopathology was performed by the Child Behavior Checklist, the Teacher's Report Form, a modified version of the ADHD-Rating Scale, the Test Observation Form, and the State-Trait Anxiety Inventory for Children. Current level of functioning was evaluated using the Children's Global Assessment Scale (CGAS). The prevalence of lifetime psychiatric diagnoses was significantly higher in both FHR-SZ children (38.7%, odds ratio, OR=3.5, 95% confidence interval, CI: 2.2-5.7, p < 0.001) and FHR-BP children (35.6%, OR=3.1, 95% CI: 1.8-5.3, p < 0.001) compared with controls (15.2%). FHR-SZ children displayed significantly more dimensional psychopathology on all scales and subscales compared with controls except for the Anxious subscale of the Test Observation Form. FHR-BP children showed higher levels of dimensional psychopathology on several scales and subscales compared with controls, but lower levels compared with FHR-SZ children. Level of functioning was lower in both FHR-SZ children (CGAS mean score = 68.2; 95% CI: 66.3-70.2, p < 0.0001) and FHR-BP children (73.7; 95% CI: 71.2-76.3, p < 0.05) compared with controls (77.9; 95% CI: 75.9-79.9). In conclusion, already at the age of seven, FHR-SZ and FHR-BP children show a higher prevalence of a broad spectrum of categorical and dimensional psychopathology compared with controls. These results emphasize the need for developing early intervention strategies towards this vulnerable group of children.

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“…As a continuum process resulting of the interaction between biological and environmental conditions, neurodevelopment occurs sequentially beginning at conception, continuing throughout pregnancy and after birth. A proper neurodevelopment sets the foundation for a child's physical and mental health, affecting not only disease incidence but socio‐emotional, language/cognitive development, and lifelong learning capacity …”

Section: Introductionmentioning

confidence: 99%

Physical activity during pregnancy and offspring neurodevelopment: A systematic review

Niño-Cruz

Varela

Silva

et al. 2018

Paediatric Perinatal Epid

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S.16.02 Schizophrenia and the neurodevelopmental continuum; new support from genomics

Cited by 32 publications

References 72 publications

Copy number variant syndromes are frequent in schizophrenia: progressing towards a CNV-schizophrenia model

Copy number variant syndromes are frequent in schizophrenia: progressing towards a CNV-schizophrenia model

Psychopathology in 7‐year‐old children with familial high risk of developing schizophrenia spectrum psychosis or bipolar disorder – The Danish High Risk and Resilience Study ‐ VIA 7, a population‐based cohort study

Physical activity during pregnancy and offspring neurodevelopment: A systematic review

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