Paus T, Keshavan M, Giedd JN. Why do many psychiatric disorders emerge during adolescence? Nat Rev Neurosci 9: 947-957

Brain & Body Centre, University of Nottingham, Nottingham, NG7 2RD, UK.
Nature Reviews Neuroscience (Impact Factor: 31.43). 01/2009; 9(12):947-57. DOI: 10.1038/nrn2513
Source: PubMed


The peak age of onset for many psychiatric disorders is adolescence, a time of remarkable physical and behavioural changes. The processes in the brain that underlie these behavioural changes have been the subject of recent investigations. What do we know about the maturation of the human brain during adolescence? Do structural changes in the cerebral cortex reflect synaptic pruning? Are increases in white-matter volume driven by myelination? Is the adolescent brain more or less sensitive to reward? Finding answers to these questions might enable us to further our understanding of mental health during adolescence.

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Available from: Matcheri Keshavan, Jul 18, 2014
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    • "Nevertheless, aversive environmental factors experienced by an individual during this window of vulnerability can also result in maladaptive changes in brain development; the qualitative and quantitative nature of which depends on various factors (Spear, 2011). Hence, it is not surprising that many adult neuropsychiatric disorders, particularly schizophrenia, have their roots in this vulnerable period (Paus et al., 2008). The gut microbiota through associated metabolic and immune activities, afford significant advantages to the host throughout development (Selkrig et al., 2014). "
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    ABSTRACT: There is growing appreciation for the importance of bacteria in shaping brain development and behaviour. Adolescence and early adulthood are crucial developmental periods during which exposure to harmful environmental factors can have a permanent impact on brain function. Such environmental factors include perturbations of the gut bacteria that may affect gut-brain communication, altering the trajectory of brain development, and increasing vulnerability to psychiatric disorders. Here we assess the effects of gut bacterial depletion from weaning onwards on adult cognitive, social and emotional behaviours and markers of gut-brain axis dysfunction in mice. Mice were treated with a combination of antibiotics from weaning onwards and effects on behaviours and potential brain-gut axis neuromodulators (tryptophan, monoamines, and neuropeptides) and BDNF expression were assessed in adulthood. Antibiotic-treatment depleted and restructured gut microbiota composition of caecal contents and decreased spleen weights in adulthood. Depletion of the gut microbiota from weaning onwards reduced anxiety, induced cognitive deficits, altered dynamics of the tryptophan metabolic pathway, and significantly reduced BDNF, oxytocin and vasopressin expression in the adult brain. Microbiota depletion from weaning onwards by means of chronic treatment with antibiotics in mice impacts on anxiety and cognitive behaviours as well as key neuromodulators of gut-brain communication in a manner that is similar to that reported in germ-free mice. This model may represent a more amenable alternative for germ-free mice in the assessment of microbiota modulation of behaviour. Finally, these data suggest that despite the presence of a normal gut microbiome in early postnatal life, reduced abundance and diversity of the gut microbiota from weaning influences adult behaviours and key neuromodulators of the microbiota-gut-brain axis suggesting that dysregulation of this axis in the post-weaning period may contribute to the pathogenesis of disorders associated with altered anxiety and cognition. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Apr 2015 · Brain Behavior and Immunity
    • "Further, there is convincing evidence that environmental influences act upon the genome by means of epigenetic mechanisms and are involved in the aetiopathogenesis of major psychoses (Rutten and Mill, 2009). In addition, genetic influences on many psychiatric and substance use disorders are likely to be dynamic, changing their action over the course of neurodevelopment; therefore, the timing of genetic effects seems to be crucial to determining different developmental outcomes (Paus et al., 2008). Indeed, the most widely held view is that neither genes nor environment are solely responsible for individual variation, and virtually all traits and diseases show gene–environment interactions (Caspi and Moffitt, 2006). "
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    ABSTRACT: Schizophrenia and other psychoses are complex disorders with high rates of cognitive impairment and a considerable degree of genetic and environmental influence on its etiology. Whether cognitive impairment is related to dimensional scores of familial liability is still matter of debate. We conducted a cross-sectional study including 169 patients with psychotic disorders and 26 healthy controls. Attention, memory and executive functions were assessed, and familial loading scores for schizophrenia and mood disorders were calculated. The relationships between familial liability and neuropsychological performance were examined with Spearman׳s correlation coefficients. In addition, patients were classified into three groups by family loading tertiles, and comparisons were performed between the patients in the top and bottom tertiles. Low familial loading scores for schizophrenia showed a significant association with poor executive functioning and delayed visual memory. And these results were also achieved when the subset of psychotic patients in the two extreme tertiles of family loadings of schizophrenia and mood disorders were compared. Low familial liability to schizophrenia seems to be a contributing factor for the severity of cognitive impairment in patients with a broad putative schizophrenia spectrum diagnosis. Copyright © 2015. Published by Elsevier Ireland Ltd.
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    • "Adolescence is associated with both increased incidence and differentiation of clinical level problem behaviors and thus has been conceptualized as a period of high risk for the development of psychopathology (Casey, Jones, & Hare, 2008; Nottelmann & Jensen, 1995; Paus, Keshavan, & Giedd, 2008). Problem behaviors during childhood and adolescence can be broadly classified into externalizing (e.g., aggression) and internalizing (e.g., depression and anxiety) problems , which commonly co-occur (Angold, Costello, & Erkanli, 1999). "
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    ABSTRACT: We examined psychopathology-neuroendocrine associations in relation to the transition into adolescence within a developmental framework that acknowledged the interdependence of the HPA and HPG hormone systems in the regulation of responses to everyday affective contexts. Saliva samples were collected during anxiety and anger inductions from 51 young adolescents (M 13.47, SD = .60 years) to evaluate cortisol, DHEA, and testosterone responses. Internalizing and externalizing problems were assessed at pre-adolescence (M = 9.27, SD = .58 years) while youths were in elementary school and concurrently with hormones in early adolescence. Externalizing problems from elementary school predicted adolescents’ reduced DHEA reactivity during anxiety induction. Follow up analyses simultaneously examining the contributions of elementary school and adolescent problems showed a trend suggesting that youths with higher levels of internalizing problems during elementary school eventuated in a profile of heightened DHEA reactivity as adolescents undergoing anxiety induction. For both the anxiety and the anger inductions, it was normative for DHEA and testosterone to be positively coupled. Adolescents with high externalizing problems but low internalizing problems marshaled dual axes co-activation during anger induction in the form of positive cortisol-testosterone coupling. This is some of the first evidence suggesting affective context determines whether dual axes coupling is reflective of normative or problematic functioning in adolescence. © 2015 Wiley Periodicals, Inc. Dev Psychobiol
    Full-text · Article · Jan 2015 · Developmental Psychobiology
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