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    • glucagon receptor antagonist While studies of depressed adul

    2018-10-29

    While studies of depressed adults have begun to tease apart the glucagon receptor antagonist regions involved in self-reflection and negative rumination, few have investigated the connectivity of these regions to better understand self-referential processing network function. Task-dependent functional connectivity analyses may help clarify the relationships between regions within this network. Only two studies to date have specifically examined task-dependent connectivity between cortical midline structures during self-referential processing in MDD, and both were also in adults. Lemogne et al. (2009) found increased connectivity between the posterior cingulate cortex and anterior regions of the DMN, including the dMPFC and ACC in depressed patients, while Yoshimura et al. (2010) found increased connectivity between the ACC, MPFC, and amygdala. One caveat of both studies was that patients were treated with psychotropic medications. Based on the above observations, the current study extends this line of work and examines self-referential processing in psychotropic medication-free adolescents with depression, as well as task-dependent connectivity of cortical midline regions within the DMN during self-referential thought. We hypothesized that adolescents with MDD would exhibit more negative self-perceptions compared to healthy controls—scores that were based on participants’ endorsement and rejection of positive and negative trait words in the scanner. Additionally, we predicted depressed adolescents would show increased activity and connectivity of cortical midlines regions (e.g., MPFC, ACC, PCC, precuneus), similarly to depressed adults (Lemogne et al., 2009, 2010, 2012; Yoshimura et al., 2010, 2014). Furthermore, we expected neural activity and connectivity in these regions to negatively correlate with self-esteem scores.
    Material and methods
    Results
    Discussion As expected, we replicated previous behavioral findings that depressed adolescents perceive themselves more negatively that healthy youth and are slower to make self-referential judgments (Gara et al., 1993; Grimm et al., 2009; Lemogne et al., 2009, 2010; Yoshimura et al., 2010). Moreover, in the entire sample, lower positive self-perceptions were related to higher depression severity, irritability, social anxiety, and anhedonia scores, emphasizing the importance of examining dimensional relationships in psychiatric research since symptoms exist along a continuum, even in the “healthy” population and are not simply present or absent. Furthermore, the depressed group was less accurate at identifying positive traits as such and categorized them more negatively, suggesting depressed adolescents may have a more globally negative perspective on personality traits in general. Additionally, despite our hypothesis that depressed adolescents would show increased activation and connectivity of cortical midline regions in response to self-referential processing, we found that all adolescents, depressed and healthy, strongly activated anterior and posterior regions within the DMN in response to self-judgments. The only region that was activated more in depressed adolescents was the PCC/precuneus in response to positive traits. Dimensional analyses revealed a significant correlation between PCC/precuneus activity and depression severity in the entire sample, further supporting the need for dimensional investigations of psychopathology. Lastly, functional connectivity of the dMPFC with local left-sided frontal regions was reduced in depressed adolescents, and was related to both illness severity and self-esteem scores in the entire sample.
    Conflict of interest
    Acknowledgments This study was supported by grants from the National Institute of Mental Health to VG (MH095807, MH101479). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIMH. The NIMH had no further role in the design, collection, management, analysis, and interpretation of data, or preparation of the manuscript.