Hulvershorn LA, Cullen K, Anand A. Toward dysfunctional connectivity: a review of neuroimaging findings in pediatric major depressive disorder. Brain Imaging Behav 5: 307-328

Mood and Emotional Disorders Across the Lifespan Center, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
Brain Imaging and Behavior (Impact Factor: 4.6). 09/2011; 5(4):307-28. DOI: 10.1007/s11682-011-9134-3
Source: PubMed


Child and adolescent psychiatric neuroimaging research typically lags behind similar advances in adult disorders. While the pediatric depression imaging literature is less developed, a recent surge in interest has created the need for a synthetic review of this work. Major findings from pediatric volumetric and functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI) and resting state functional connectivity studies converge to implicate a corticolimbic network of key areas that work together to mediate the task of emotion regulation. Imaging the brain of children and adolescents with unipolar depression began with volumetric studies of isolated brain regions that served to identify key prefrontal, cingulate and limbic nodes of depression-related circuitry elucidated from more recent advances in DTI and functional connectivity imaging. Systematic review of these studies preliminarily suggests developmental differences between findings in youth and adults, including prodromal neurobiological features, along with some continuity across development.

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    • "We used a task-based approach (vs. resting-state connectivity) to examine neural coactivation in response to an event or stimulus because we were interested in depression-related neurobiological differences in reward circuitry during rewarding events (Davey et al., 2008; Forbes & Dahl, 2012; Hulvershorn, Cullen, & Anand, 2011). "
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    ABSTRACT: Given that depression in men is associated with risk for seriously adverse consequences, evaluating how putative neural mechanisms of depression-such as reward-related frontostriatal connectivity-may be altered in late adolescent boys with a history of depression is an important research aim. Adolescents and adults with depression have been demonstrated to show blunted striatal response and heightened medial prefrontal cortex (mPFC) activation to winning reward. Function in reward circuits appears to be best understood as coordination of regions within frontostriatal circuitry, and alterations to this circuitry could occur in those with a history of depression. The current study evaluated functional connectivity between the nucleus accumbens and mPFC in a sample of 166 ethnically diverse boys with and without a history of depression. Participants completed an fMRI monetary reward paradigm at age 20. Lifetime history of depression and other psychiatric illnesses was measured prospectively and longitudinally, using structured clinical interviews at 7 time points from ages 8 to 20. Boys with a history of depression showed heightened positive connectivity between the nucleus accumbens and the mPFC relative to boys with no psychiatric history when winning rewards relative to losing rewards. This altered frontostriatal connectivity pattern was also associated with greater number of depressive episodes in the boys' lifetime. History of depression in late adolescent boys may be associated with altered coordination between the nucleus accumbens and mPFC when winning reward. This coordination could reflect oversignaling of the mPFC to dampen typical ventral striatum response or enhance weak ventral striatum response.
    Full-text · Article · Apr 2015 · Journal of Clinical Child & Adolescent Psychology
    • "– – Neuroimaging studies (for a review of neuroimaging studies in paediatric depression see [42, 45]). "
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    ABSTRACT: Numerous studies have shown that Major Depressive Disorder (MDD) in adults is associated with deficits in cognitive control. Particularly, impairment on executive function (EF) tasks has been observed. Research into EF deficits in children and adolescents with MDD has reported mixed results and it is currently unclear whether paediatric MDD is characterised by impairments in EF and attention. PsycInfo, Scopus and Medline were systematically searched to identify all studies that have investigated EF and attention in paediatric depressive disorders between 1994 and 2014. 33 studies meeting inclusion/exclusion criteria were identified. While across different domains of EF some studies identified a deficit in the clinical group, the majority of studies failed to find deficits in response inhibition, attentional set shifting, selective attention, verbal working memory, and verbal fluency. More research is needed to clarify the relationship between depressive disorders in children and adolescents and spatial working memory processing, sustaining attention, planning, negative attentional bias and measures of 'hot' EF. There is little support for EF deficits in paediatric depression. However, there are numerous methodological problems that may account for null findings. Alternatively, chronicity and/or severity of symptoms may explain discrepancies between cognitive deficits in adult and paediatric MDD. Recommendations for future studies are discussed.
    No preview · Article · Jan 2015 · European Child & Adolescent Psychiatry
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    • "10 D.I. Lubman et al. / Pharmacology & Therapeutics xxx (2014) xxx–xxx Please cite this article as: Lubman, D.I., et al., Cannabis and adolescent brain development, Pharmacology & Therapeutics (2014), 10.1016/j.pharmthera.2014.11.009 Hulvershorn et al., 2011; Tham et al., 2011), and there is evidence that heavy cannabis use may speed up or worsen these changes amongst affected individuals (Medina et al., 2007b; Solowij et al., 2011b). However to date, there have been few studies that have prospectively examined associations between adolescent cannabis exposure, altered trajectories of brain development, and psychiatric or cognitive impairment in adulthood . "
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    ABSTRACT: Heavy cannabis use has been frequently associated with increased rates of mental illness and cognitive impairment, particularly amongst adolescent users. However, the neurobiological processes that underlie these associations are still not well understood. In this review, we discuss the findings of studies examining the acute and chronic effects of cannabis use on the brain, with a particular focus on the impact of commencing use during adolescence. Accumulating evidence from both animal and human studies suggests that regular heavy use during this period is associated with more severe and persistent negative outcomes than use during adulthood, suggesting that the adolescent brain may be particularly vulnerable to the effects of cannabis exposure. As the endocannabinoid system plays an important role in brain development, it is plausible that prolonged use during adolescence results in a disruption in the normative neuromaturational processes that occur during this period. We identify synaptic pruning and white matter development as two processes that may be adversely impacted by cannabis exposure during adolescence. Potentially, alterations in these processes may underlie the cognitive and emotional deficits that have been associated with regular use commencing during adolescence.
    Full-text · Article · Nov 2014 · Pharmacology [?] Therapeutics
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