Cohort Profile: The NSPN 2400 Cohort: a developmental sample supporting the Wellcome Trust NeuroScience in Psychiatry Network

Kiddle, Beatrix; Inkster, Becky; Prabhu, Gita; Moutoussis, Michael; Whitaker, Kirstie; Bullmore, Edward T.; Dolan, Raymond J.; Fonagy, Peter; Goodyer, Ian; Jones, Peter

doi:10.1093/ije/dyx117

Cited by 92 publications

(154 citation statements)

References 47 publications

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“…Sample 2135 healthy young people, aged 14-25 years, were recruited from schools, colleges, NHS primary care services and direct advertisement in north London and Cambridgeshire, UK. This primary cohort was stratified into 5 contiguous age-related strata, balanced for sex and ethnicity (28). A secondary cohort of N=297 was recruited by randomly sub-sampling the primary cohort so that ~60 participants were assigned to each of the same age-related strata, balanced for sex and ethnicity, as in the primary cohort.…”

Section: Methodsmentioning

confidence: 99%

Schizotypy-related magnetization of cortex in healthy adolescence is co-located with expression of schizophrenia-related genes

Romero-García

Seidlitz

Whitaker

et al. 2018

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= 249 words (max 250 words) Main text = 3997 words (max 4000 words). References = 72 Figures = 4 Table = 1 Intra-cortical magnetization and patterning of schizophrenia-related genes 2 Abstract Background Genetic risk is thought to drive clinical variation on a spectrum of schizophrenia-like traits but the underlying changes in brain structure that mechanistically link genomic variation to schizotypal experience and behaviour are unclear. MethodsWe assessed schizotypy using a self-reported questionnaire, and measured magnetization transfer (MT), as a putative micro-structural MRI marker of intra-cortical myelination, in 68 brain regions, in 248 healthy young people (aged 14-25 years). We used normative adult brain gene expression data, and partial least squares (PLS) analysis, to find the weighted gene expression pattern that was most co-located with the cortical map of schizotypy-related magnetization (SRM). ResultsMagnetization was significantly correlated with schizotypy in bilateral posterior cingulate cortex and precuneus (and for disorganized schizotypy also in medial prefrontal cortex; all FDR-corrected P < 0.05), which are regions of the default mode network specialized for social and memory functions. The genes most positively weighted on the whole genome expression map co-located with SRM were enriched for genes that were significantly downregulated in two prior case-control histological studies of brain gene expression in schizophrenia. Conversely, the most negatively weighted genes were enriched for genes that were transcriptionally up-regulated in schizophrenia. Positively weighted (downregulated) genes were enriched for neuronal, specifically inter-neuronal, affiliations and coded a network of proteins comprising a few highly interactive "hubs" such as parvalbumin and calmodulin. ConclusionsMicrostructural MRI maps of intracortical magnetization can be linked to both the behavioural traits of schizotypy and to prior histological data on dysregulated gene expression in schizophrenia. previous version of this paper was posted on bioRxiv: https://www.biorxiv.org/content/10.1101/487108v1 DATA and CODE SHARING DataRegional magnetisation transfer (MT) for 68 cortical regions, schizotypy scores, age, gender, socio-economic status, scanning site, total brain volume and Euler values, for N=248, are available at: https://github.com/RafaelRomeroGarcia/Schizotypy_MT_geneExp. CodeCortical parcellation of gene expression maps to estimate regional mean gene expression (62): (https://github.com/RafaelRomeroGarcia/geneExpression_Repository) Generate null-models that preserve the spatial contiguity of cortical regions for permutation testing (31): https://github.com/frantisekvasa/rotate_parcellation PLS analysis and bootstrapping to estimate PLS weights (15): https://github.com/KirstieJane/NSPN_WhitakerVertes_PNAS2016/tree/master/SCRIPTS Generate Figure S1 from raw Gandal (5) and Fromer (49) datasets: https://github.com/RafaelRomeroGarcia/Schizotypy_MT_geneExpMapping regional values to the cortical surface for visuali...

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Section: Methodsmentioning

confidence: 99%

Schizotypy-related magnetization of cortex in healthy adolescence is co-located with expression of schizophrenia-related genes

Romero-García

Seidlitz

Whitaker

et al. 2018

Preprint

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“…harsh parenting or neglect) from those of 160 positive ones (e.g., parental warmth or praise; see Methods). Component negative and positive 161 scores were derived from three self-report questionnaires (Kiddle et al, 2017). We found that 162 parenting quality was not associated with MTr and thus could not mediate the effect of SED on MTr 163…”

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confidence: 89%

“…Abbreviated Scale Intelligence of (WASI) (Kiddle et al, 2017). As ours was a developmental study, we 309 used the raw subscale scores for vocabulary and matrix IQ and explicitly analysed, and their 310 dependence of age.…”

Section: Recruitment Demographic and Psychological Measures 296mentioning

confidence: 99%

“…Questionnaire (PPQ), Alabama Parenting Questionnaire (APQ) and Measure of Parenting Style 314 (MOPS). All three were obtained within about a month of the first scan (Kiddle et al, 2017). We took 315 the reversed positive parenting total score from the PPQ and the similarly reversed positive parenting 316 scales from the APQ, the negative parenting scales from the APQ (inconsistent discipline, poor 317 supervision, and corporal punishment) and the negative parenting scores for the MOPS (abuse, control 318 and neglect), which were standardized and summed to make a composite negative parenting scale.…”

Section: Recruitment Demographic and Psychological Measures 296mentioning

confidence: 99%

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Childhood socio-economic disadvantage predicts reduced myelin growth across adolescence and young adulthood

Ziegler

Moutoussis

Hauser

et al. 2019

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37Socio-economic disadvantage (SED) increases exposure to life stressors. Animal research suggests 38 early life stressors affect later neurodevelopment, including myelin developmental growth. To 39 determine whether human childhood SED affects myelination in adolescence and early adulthood we 40 measured the developmental increase of a sensitive myelin marker, magnetization transfer (MT), in a 41 longitudinal study. Childhood SED was associated with globally reduced MT, as well as slower intra-42 cortical MT increase in widespread sensory-motor, cingulate, insular and prefrontal areas and 43 subcortical areas. Parental education partially accounted for the SED effects on MT increase, while 44 positive parenting provided a partial protection against the impact of SED. Thus, early socio-economic 45 disadvantage, a vulnerability factor for a range of ill-health outcomes, is a risk factor for aberrant 46 myelin growth during a critical developmental period that is associated with a high risk of psychiatric 47 disorder. 48 49 Keywords 50 Myelin, magnetization transfer, development, quantitative imaging, socio-economic disadvantage, 51 adolescence, young adulthood, parenting, parental education, longitudinal 52 53 54

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“…We contacted all individuals from the Neuroscience in Psychiatry Network (NSPN), a longitudinal population-based cohort study examining brain development (Kiddle et al, 2017), via email. Participants completed an online survey implemented in SurveyMonkey in 2018 and had also provided baseline questionnaires via the post (2012)(2013)(2014).…”

Section: Participantsmentioning

confidence: 99%

Fractionation of impulsive and compulsive trans-diagnostic phenotypes and their longitudinal associations

Chamberlain

Tiego

Fontenelle

et al. 2019

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Objective: Young adulthood is a crucial neurodevelopmental period during which impulsive and compulsive problem behaviours commonly emerge. While traditionally considered diametrically opposed, impulsive and compulsive symptoms tend to co-occur. The objectives of this study were: (i) to identify the optimal trans-diagnostic structural framework for measuring impulsive and compulsive problem behaviours; and (ii) to use this optimal framework to identify common/distinct antecedents of these latent phenotypes.Methods: 654 young adults were recruited as part of the Neuroscience in Psychiatry Network (NSPN), a population-based cohort in the United Kingdom. The optimal trans-diagnostic structural model capturing 33 types of impulsive and compulsive problem behaviours was identified. Baseline predictors of subsequent impulsive and compulsive trans-diagnostic phenotypes were characterised, along with cross-sectional associations, using Partial Least Squares (PLS).Results: Current problem behaviours were optimally explained by a bi-factor model, which yielded dissociable measures of impulsivity and compulsivity, as well as a general disinhibition factor. Impulsive problem behaviours were significantly explained by prior antisocial and impulsive personality traits, male gender, general distress, perceived dysfunctional parenting, and teasing/arguments within friendships. Compulsive problem behaviours were significantly explained by prior compulsive traits, and female gender.Conclusions: This study demonstrates that trans-diagnostic phenotypes of 33 impulsive and compulsive problem behaviours are identifiable in young adults, utilizing a bi-factor model based on responses to a single questionnaire. Furthermore, these phenotypes have different antecedents. The findings yield a new framework for fractionating impulsivity and compulsivity; and suggest different early intervention targets to avert emergence of problem behaviours. This framework may be useful for future biological and clinical dissection of impulsivity and compulsivity.

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Cohort Profile: The NSPN 2400 Cohort: a developmental sample supporting the Wellcome Trust NeuroScience in Psychiatry Network

Cited by 92 publications

References 47 publications

Schizotypy-related magnetization of cortex in healthy adolescence is co-located with expression of schizophrenia-related genes

Schizotypy-related magnetization of cortex in healthy adolescence is co-located with expression of schizophrenia-related genes

Childhood socio-economic disadvantage predicts reduced myelin growth across adolescence and young adulthood

Fractionation of impulsive and compulsive trans-diagnostic phenotypes and their longitudinal associations

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