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  • ItemPublished versionOpen Access
    Adolescent Tuning of Association Cortex in Human Structural Brain Networks
    (Oxford University Press, 2018-01-01) Vasa, F; Seidlitz, J; Romero Garcia, R; Whitaker, KJ; Rosenthal, G; Vertes, P; Shinn, M; Alexander-Bloch, A; Fonagy, P; Dolan, R; Jones, P; Goodyer, I; NSPN Consortium; Sporns, O; Bullmore, ET; Seidlitz, Jakob [0000-0002-8164-7476]; Romero Garcia, Rafael [0000-0002-5199-4573]; Whitaker, Kirstie [0000-0001-8498-4059]; Vertes, Petra [0000-0002-0992-3210]; Jones, Peter [0000-0002-0387-880X]; Goodyer, Ian [0000-0001-9183-0373]; Bullmore, Edward [0000-0002-8955-8283]
    Motivated by prior data on local cortical shrinkage and intracortical myelination, we predicted age-related changes in topological organization of cortical structural networks during adolescence. We estimated structural correlation from magnetic resonance imaging measures of cortical thickness at 308 regions in a sample of N = 297 healthy participants, aged 14–24 years. We used a novel sliding-window analysis to measure age-related changes in network attributes globally, locally and in the context of several community partitions of the network. We found that the strength of structural correlation generally decreased as a function of age. Association cortical regions demonstrated a sharp decrease in nodal degree (hubness) from 14 years, reaching a minimum at approximately 19 years, and then levelling off or even slightly increasing until 24 years. Greater and more prolonged age-related changes in degree of cortical regions within the brain network were associated with faster rates of adolescent cortical myelination and shrinkage. The brain regions that demonstrated the greatest age-related changes were concentrated within prefrontal modules. We conclude that human adolescence is associated with biologically plausible changes in structural imaging markers of brain network organization, consistent with the concept of tuning or consolidating anatomical connectivity between frontal cortex and the rest of the connectome.
  • ItemPublished versionOpen Access
    Characterising the latent structure and organisation of self-reported thoughts, feelings and behaviours in adolescents and young adults
    (PLOS, 2017-04-12) St Clair, MC; Neufeld, S; Jones, PB; Fonagy, P; Bullmore, ET; Dolan, RJ; Moutoussis, M; Toseeb, U; Goodyer, IM; Neufeld, Sharon [0000-0001-5470-3770]; Jones, Peter [0000-0002-0387-880X]; Bullmore, Edward [0000-0002-8955-8283]; Goodyer, Ian [0000-0001-9183-0373]
    Little is known about the underlying relationships between self-reported mental health items measuring both positive and negative emotional and behavioural symptoms at the population level in young people. Improved measurement of the full range of mental well-being and mental illness may aid in understanding the aetiological substrates underlying the development of both mental wellness as well as specific psychiatric diagnoses. A general population sample aged 14 to 24 years completed self-report questionnaires on anxiety, depression, psychotic-like symptoms, obsessionality and well-being. Exploratory and confirmatory factor models for categorical data and latent profile analyses were used to evaluate the structure of both mental wellness and illness items. First order, second order and bifactor structures were evaluated on 118 self-reported items obtained from 2228 participants. A bifactor solution was the best fitting latent variable model with one general latent factor termed 'distress' and five 'distress independent' specific factors defined as self-confidence, antisocial behaviour, worry, aberrant thinking, and mood. Next, six distinct subgroups were derived from a person-centred latent profile analysis of the factor scores. Finally, concurrent validity was assessed using information on hazardous behaviours (alcohol use, substance misuse, self-harm) and treatment for mental ill health: both discriminated between the latent traits and latent profile subgroups. The findings suggest a complex, multidimensional mental health structure in the youth population rather than the previously assumed first or second order factor structure. Additionally, the analysis revealed a low hazardous behaviour/low mental illness risk subgroup not previously described. Population sub-groups show greater validity over single variable factors in revealing mental illness risks. In conclusion, our findings indicate that the structure of self reported mental health is multidimensional in nature and uniquely finds improved prediction to mental illness risk within person-centred subgroups derived from the multidimensional latent traits.
  • ItemAccepted versionOpen Access
    Cohort profile: The NSPN 2400 Cohort: a developmental sample supporting the Wellcome Trust NeuroScience in Psychiatry Network
    (Oxford University Press, 2018-02-01) Kiddle, B; Inkster, B; Prabhu, G; Moutoussis, M; Whitaker, KJ; NSPN Consortium; Bullmore, ET; Dolan, RJ; Fonagy, P; Goodyer, IM; Jones, PB; Whitaker, Kirstie [0000-0001-8498-4059]; Bullmore, Edward [0000-0002-8955-8283]; Goodyer, Ian [0000-0001-9183-0373]; Jones, Peter [0000-0002-0387-880X]
    Mental and substance use disorders are the leading cause of years lived with disability, worldwide. Other than childhood developmental disorders and neurodegenerative dementias of the elderly, most mental health disorders are first manifest in the second and third decades of life during which the highest proportion of total disability adjusted life years occurs due to their enormous impact on normal, adolescent and young adult functioning; non-syndromal abnormalities can be identified far earlier in life.
  • ItemPublished versionOpen Access
    Gene transcription profiles associated with inter-modular hubs and connection distance in human functional magnetic resonance imaging networks.
    (The Royal Society, 2016-10-05) Vértes, Petra E; Rittman, Timothy; Whitaker, Kirstie J; Romero-Garcia, Rafael; Váša, František; Kitzbichler, Manfred G; Wagstyl, Konrad; Fonagy, Peter; Dolan, Raymond J; Jones, Peter B; Goodyer, Ian M; NSPN Consortium; Bullmore, Edward T; Kitzbichler, Manfred G [0000-0002-4494-0753]; Bullmore, Edward T [0000-0002-8955-8283]
    Human functional magnetic resonance imaging (fMRI) brain networks have a complex topology comprising integrative components, e.g. long-distance inter-modular edges, that are theoretically associated with higher biological cost. Here, we estimated intra-modular degree, inter-modular degree and connection distance for each of 285 cortical nodes in multi-echo fMRI data from 38 healthy adults. We used the multivariate technique of partial least squares (PLS) to reduce the dimensionality of the relationships between these three nodal network parameters and prior microarray data on regional expression of 20 737 genes. The first PLS component defined a transcriptional profile associated with high intra-modular degree and short connection distance, whereas the second PLS component was associated with high inter-modular degree and long connection distance. Nodes in superior and lateral cortex with high inter-modular degree and long connection distance had local transcriptional profiles enriched for oxidative metabolism and mitochondria, and for genes specific to supragranular layers of human cortex. In contrast, primary and secondary sensory cortical nodes in posterior cortex with high intra-modular degree and short connection distance had transcriptional profiles enriched for RNA translation and nuclear components. We conclude that, as predicted, topologically integrative hubs, mediating long-distance connections between modules, are more costly in terms of mitochondrial glucose metabolism.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'.
  • ItemAccepted versionOpen Access
    Adolescence is associated with genomically patterned consolidation of the hubs of the human brain connectome.
    (Proceedings of the National Academy of Sciences, 2016-08-09) Whitaker, Kirstie J; Vértes, Petra E; Romero-Garcia, Rafael; Váša, František; Moutoussis, Michael; Prabhu, Gita; Weiskopf, Nikolaus; Callaghan, Martina F; Wagstyl, Konrad; Rittman, Timothy; Tait, Roger; Ooi, Cinly; Suckling, John; Inkster, Becky; Fonagy, Peter; Dolan, Raymond J; Jones, Peter B; Goodyer, Ian M; NSPN Consortium; Bullmore, Edward T; Whitaker, Kirstie J [0000-0001-8498-4059]; Vértes, Petra E [0000-0002-0992-3210]; Bullmore, Edward T [0000-0002-8955-8283]
    How does human brain structure mature during adolescence? We used MRI to measure cortical thickness and intracortical myelination in 297 population volunteers aged 14-24 y old. We found and replicated that association cortical areas were thicker and less myelinated than primary cortical areas at 14 y. However, association cortex had faster rates of shrinkage and myelination over the course of adolescence. Age-related increases in cortical myelination were maximized approximately at the internal layer of projection neurons. Adolescent cortical myelination and shrinkage were coupled and specifically associated with a dorsoventrally patterned gene expression profile enriched for synaptic, oligodendroglial- and schizophrenia-related genes. Topologically efficient and biologically expensive hubs of the brain anatomical network had greater rates of shrinkage/myelination and were associated with overexpression of the same transcriptional profile as cortical consolidation. We conclude that normative human brain maturation involves a genetically patterned process of consolidating anatomical network hubs. We argue that developmental variation of this consolidation process may be relevant both to normal cognitive and behavioral changes and the high incidence of schizophrenia during human brain adolescence.
  • ItemOpen Access
    Inflammation and immunity in schizophrenia: implications for pathophysiology and treatment.
    (Elsevier BV, 2015-03) Khandaker, Golam M; Cousins, Lesley; Deakin, Julia; Lennox, Belinda R; Yolken, Robert; Jones, Peter B; Khandaker, Golam [0000-0002-4935-9220]; Jones, Peter [0000-0002-0387-880X]
    Complex interactions between the immune system and the brain might have important aetiological and therapeutic implications for neuropsychiatric brain disorders. A possible association between schizophrenia and the immune system was postulated over a century ago, and is supported by epidemiological and genetic studies pointing to links with infection and inflammation. Contrary to the traditional view that the brain is an immunologically privileged site shielded behind the blood-brain barrier, studies in the past 20 years have noted complex interactions between the immune system, systemic inflammation, and the brain, which can lead to changes in mood, cognition, and behaviour. In this Review, we describe some of the important areas of research regarding innate and adaptive immune response in schizophrenia and related psychotic disorders that, we think, will be of interest to psychiatric clinicians and researchers. We discuss potential mechanisms and therapeutic implications of these findings, including studies of anti-inflammatory drugs in schizophrenia, describe areas for development, and offer testable hypotheses for future investigations.