Article

Why do many psychiatric disorders emerge during adolescence?

Brain & Body Centre, University of Nottingham, Nottingham, NG7 2RD, UK.
Nature Reviews Neuroscience (Impact Factor: 31.38). 01/2009; 9(12):947-57. DOI: 10.1038/nrn2513
Source: PubMed

ABSTRACT 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.
    Brain Behavior and Immunity 04/2015; DOI:10.1016/j.bbi.2015.04.004 · 6.13 Impact Factor
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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
    Developmental Psychobiology 01/2015; DOI:10.1002/dev.21268 · 3.16 Impact Factor
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    • "To better understand the neural changes associated with MDD in adolescence , we examined cross-sectional differences in brain structure associated in a large sample of adolescents compared with healthy age-and gender-matched controls. Acknowledging that first episodes occur prior to age 18 years in an estimated 25% of adult individuals with mood disorders and that age (and associated neurobiological changes) plays a key role in the aetiology of mental illness (Jones, 2013), and depression in particular (Whittle et al., 2014), we examined differences in GMV between groups of adolescents with current depression and and healthy controls taking the putative effects of age on GMV into account (Paus et al., 2008). Given that the most common finding in adults with MDD is reduced GMV in pregenual ACC (Bora et al., 2012), a region important to both the onset and course of depressive illness (Chen et al., 2007), we predicted that adolescents with MDD would show reduced GMV in this region relative to healthy adolescents irrespective of age-dependent change. "
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    ABSTRACT: Objective There is little understanding of the neural system abnormalities subserving adolescent major depressive disorder (MDD). In a cross-sectional study we compare currently unipolar depressed with healthy adolescents to determine if group differences in grey matter volume (GMV) were influenced by age and illness severity. Method Structural neuroimaging was performed on 109 adolescents with current MDD and 36 healthy controls, matched for age, gender, and handedness. GMV differences were examined within the anterior cingulate cortex (ACC) and across the whole-brain. The effects of age and self-reported depressive symptoms were also examined in regions showing significant main or interaction effects. Results Whole-brain voxel based morphometry revealed no significant group differences. At the whole-brain level, both groups showed a main effect of age on GMV, although this effect was more pronounced in controls. Significant group-by-age interactions were noted: A significant regional group-by-age interaction was observed in the ACC. GMV in the ACC showed patterns of age-related differences that were dissimilar between adolescents with MDD and healthy controls. GMV in the thalamus showed an opposite pattern of age-related differences in adolescent patients compared to healthy controls. In patients, GMV in the thalamus, but not the ACC, was inversely related with self-reported depressive symptoms. Conclusions The depressed adolescent brain shows dissimilar age-related and symptom-sensitive patterns of GMV differences compared with controls. The thalamus and ACC may comprise neural markers for detecting these effects in youth. Further investigations therefore need to take both age and level of current symptoms into account when disaggregating antecedent neural vulnerabilities for MDD from the effects of MDD on the developing brain.
    01/2015; 7:391-399. DOI:10.1016/j.nicl.2014.12.019
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