Default mode network connectivity in children with a history of preschool onset depression

Department of Psychiatry, Washington University in St. Louis, Saint Louis, MO 63110, USA.
Journal of Child Psychology and Psychiatry (Impact Factor: 6.46). 04/2012; 53(9):964-72. DOI: 10.1111/j.1469-7610.2012.02552.x
Source: PubMed


Atypical Default Mode Network (DMN) functional connectivity has been previously reported in depressed adults. However, there is relatively little data informing the developmental nature of this phenomenon. The current case-control study examined the DMN in a unique prospective sample of school-age children with a previous history of preschool depression.
DMN functional connectivity was assessed using resting state functional connectivity magnetic resonance imaging data and the posterior cingulate (PCC) as a seed region of interest. Thirty-nine medication naïve school age children (21 with a history of preschool depression and 18 healthy peers) and their families who were ascertained as preschoolers and prospectively assessed over at least 4 annual waves as part of a federally funded study of preschool depression were included.
  Decreased connectivity between the PCC and regions within the middle temporal gyrus (MTG), inferior parietal lobule, and cerebellum was found in children with known depression during the preschool period. Increased connectivity between the PCC and regions within the subgenual and anterior cingulate cortices and anterior MTG bilaterally was also found in these children. Additionally, a clinically relevant 'brain-behavior' relationship between atypical functional connectivity of the PCC and disruptions in emotion regulation was identified.
To our knowledge, this is the first study to examine the DMN in children known to have experienced the onset of a clinically significant depressive syndrome during preschool. Results suggest that a history of preschool depression is associated with atypical DMN connectivity. However, longitudinal studies are needed to clarify whether the current findings of atypical DMN connectivity are a precursor or a consequence of preschool depression.

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    • "In summary, prior studies provide inconsistent reports of RSC among amygdala (Dickstein et al., 2010; Luking et al., 2011), striatal (Bluhm et al., 2009; Davey et al., 2012; Gabbay et al., 2013; Xiao et al., 2013), prefrontal cortical (Cao et al., 2006; Cullen et al., 2009; Dickstein et al., 2010; Davey et al., 2012; Sun et al., 2012; Wu et al., 2013), anterior cingulate cortical (Bluhm et al., 2009; Cullen et al., 2009; Davey et al., 2012; Gaffrey et al., 2012; Gabbay et al., 2013; Wu et al., 2013; Xiao et al., 2013), and insula (Wu et al., 2013) regions in behaviorally and emotionally dysregulated youth. In the present study, we aimed to elucidate for the first time the nature and extent of relationships between pathological dimensions and RSC versus relationships between diagnostic categories and RSC in a clinical cohort of youth with behavioral and emotional dysregulation. "
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    ABSTRACT: The Research Domain Criteria (RDoC) adopts a dimensional approach for examining pathophysiological processes underlying categorically defined psychiatric diagnoses. We used this framework to examine relationships among symptom dimensions, diagnostic categories, and resting state connectivity in behaviorally and emotionally dysregulated youth selected from the Longitudinal Assessment of Manic Symptoms study (n=42) and healthy control youth (n=18). Region of interest analyses examined relationships among resting state connectivity, symptom dimensions (behavioral and emotional dysregulation measured with the Parent General Behavior Inventory-10 Item Mania Scale [PGBI-10M]; dimensional severity measures of mania, depression, anxiety), and diagnostic categories (Bipolar Spectrum Disorders, Attention Deficit Hyperactivity Disorder, Anxiety Disorders, and Disruptive Behavior Disorders). After adjusting for demographic variables, two dimensional measures showed significant inverse relationships with resting state connectivity, regardless of diagnosis: 1) PGBI-10M with amygdala-left posterior insula/bilateral putamen; and 2) depressive symptoms with amygdala-right posterior insula connectivity. Diagnostic categories showed no significant relationships with resting state connectivity. Resting state connectivity between amygdala and posterior insula decreased with increasing severity of behavioral and emotional dysregulation and depression; this suggests an intrinsic functional uncoupling of key neural regions supporting emotion processing and regulation. These findings support the RDoC dimensional approach for characterizing pathophysiologic processes that cut across different psychiatric disorders. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Psychiatry Research: Neuroimaging 11/2014; 231(1). DOI:10.1016/j.pscychresns.2014.10.015 · 2.42 Impact Factor
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    • "Furthermore, the variance in medication history among subjects could be a significant confounding factor (Wang, Hermens, Hickie, & and anxiety, in adults (Broyd et al., 2009; Sylvester et al., 2012). A recent RSFC study in children with preschool onset depression also found aberrancies in DMN connectivity, reporting decreased connectivity between the posterior cingulate cortex (PCC) and temporal and parietal cortical areas as well as the cerebellum, and increased connectivity between the PCC and subgenual anterior cortical areas (Gaffrey et al., 2012). Studies investigating the developmental course of resting-state connectivity networks observed a change in connectivity patterns of these networks over time. "
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    ABSTRACT: Background Depression is prevalent and typically has its onset in adolescence. Resting-state fMRI could help create a better understanding of the underlying neurobiological mechanisms during this critical period. In this study, resting-state functional connectivity (RSFC) is examined using seed regions-of-interest (ROIs) associated with three networks: the limbic network, the default mode network (DMN) and the salience network.Methods Twenty-six treatment-naïve, clinically depressed adolescents of whom 18 had comorbid anxiety, and 26 pair-wise matched healthy controls underwent resting-state fMRI. The three networks were investigated using a seed-based ROI approach with seeds in the bilateral amygdala (limbic network), bilateral dorsal anterior cingulate cortex (dACC; salience network) and bilateral posterior cingulate cortex (default mode network).ResultsCompared to healthy controls, clinically depressed adolescents showed increased RSFC of the left amygdala with right parietal cortical areas, and decreased right amygdala RSFC with left frontal cortical areas including the ACC, as well as with right occipito-parietal areas. The bilateral dACC showed decreased RSFC with the right middle frontal gyrus, frontal pole, and inferior frontal gyrus in clinically depressed adolescents. No abnormalities in DMN RSFC were found, and differences in RSFC did not correlate with clinical measures.Conclusions The aberrant RSFC of the amygdala network and the dACC network may be related to altered emotion processing and regulation in depressed adolescents. Our results provide new insights into RSFC in clinically depressed adolescents and future models on adolescent depression may include abnormalities in the connectivity of salience network.
    Journal of Child Psychology and Psychiatry 05/2014; 55(12). DOI:10.1111/jcpp.12266 · 6.46 Impact Factor
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    • "Moreover, children with depression show weaker connectivity between the amygdala and prefrontal cortex than do healthy children (Luking et al., 2011). Whereas the amygdala–prefrontal circuit is characterized by reduced connectivity in pediatric depression, within the default network, children with a history of preschool depression show increased posterior–anterior connectivity (between posterior cingulate and subgenual anterior cingulate cortices; Gaffrey et al., 2012). Stronger functional connection between posterior–anterior default network relates to worse emotional regulation and coping for both sadness and anger in children with preschool-onset depression but only sadness for controls (Gaffrey, Luby, Botteron, Repovs, & Barch, 2012). "
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    ABSTRACT: The development of socioemotional functioning is a complex process that occurs over a protracted time period and requires coordinating affective, cognitive, and social faculties. At many points in development, the trajectory of socioemotional development can be deleteriously altered due to a combination of environmental insults and individual vulnerabilities. The result can be psychopathology. However, researchers are just beginning to understand the neural and genetic mechanisms involved in the development of healthy and disordered socioemotional functioning. We propose a translational developmental neuroscience framework to understand the transactional process that results in socioemotional functioning in both healthy and disordered populations. We then apply this framework to healthy socioemotional development, pediatric anxiety, pediatric depression, and autism spectrum disorder, selectively reviewing current literature in light of the framework. Finally, we examine ways that the framework can help to frame future directions of research on socioemotional development and translational implications for intervention.
    Development and Psychopathology 11/2013; 25(4 Pt 2):1293-309. DOI:10.1017/S095457941300062X · 4.89 Impact Factor
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