Brain structural thickness and resting state autonomic function in adolescents with major depression

Abstract

Major depressive disorder (MDD) has been associated with abnormalities in cortical thickness and autonomic function. Adolescence is a time notable for brain development and MDD onset. In healthy adolescents, greater resting state vagal activity (RVA) is associated with lower cortical thickness. The relationship between brain structural thickness and RVA in adolescents with MDD has not previously been studied. This secondary analysis drew on a sample of 37 non-depressed controls and 53 adolescents with MDD. Resting state heart rate and two indices of RVA (HF-HRV and RMSSD) were recorded during a neuroimaging session. Cortical thickness within fronto-limbic regions of interest was measured using Freesurfer analysis of T1-weighted high-resolution structural images. Self-reports of depression severity showed a significant interaction with cortical thickness of the right insula in predicting RMSSD [t = 2.22, P=0.030, β = 5.44; model fit of the interaction term as indicated by the ‘Bayes Factor’ (BF): 7.58] and HF-HRV (t = 2.09, P=0.041, β = 4.72; BF: 7.94). Clinician ratings of depression severity showed further interactions. Findings underscore the important relationships between RVA and cortical development, suggesting two possible explanations: (i) in adolescent MDD, greater fronto-limbic thickness is compensatory for deficits in autonomic regulation or (ii) increased autonomic arousal results in delayed fronto-limbic maturation. Longitudinal research is necessary to further clarify the nature of the relationship between autonomic functioning and cortical development.

Increases in orbitofrontal cortex thickness following antidepressant treatment are associated with changes in resting state autonomic function in adolescents with major depression – Preliminary findings from a pilot study

“…Interestingly, we have previously reported a general pattern of inverse associations between HRV and cortical thickness (not including the OFC) in healthy non-depressed adolescents (Koenig et al, 2017a). This pattern was inverted (i.e., positive association between HRV and cortical thickness) in depressed adolescents (Koenig et al 2018), similar to findings in adults (Winkelmann et al, 2016; Wood et al, 2017; Yoo et al, 2017). We previously suggested a compensatory mechanism where increased cortical thickness in adolescent MDD may facilitate maintenance of autonomic function (Koenig et al 2018).…”

“…This pattern was inverted (i.e., positive association between HRV and cortical thickness) in depressed adolescents (Koenig et al 2018), similar to findings in adults (Winkelmann et al, 2016; Wood et al, 2017; Yoo et al, 2017). We previously suggested a compensatory mechanism where increased cortical thickness in adolescent MDD may facilitate maintenance of autonomic function (Koenig et al 2018). The present findings add that effective SSRI treatment does not normalize the pattern of association between HRV and thickness, but seems to support the hypothesis that a compensatory mechanism is at play via increases in cortical thickness in the OFC.…”

Cortical morphometric predictors of autonomic dysfunction in generalized anxiety disorder

“…To conclude, this is not the first study that has described disrupted cortico-autonomic integration in psychopathological disorders (e.g., Koenig et al, 2018a for major depression;…”

Neurovisceral regulatory circuits of affective resilience in youth

“…For example, changes in cortical thickness in relation to depression have been shown to be observable only in adults, not adolescents (Schmaal et al, 2017). Studying potential differences in the association between brain structure and vagal activity in adolescents with MDD and controls, we found that cortical thickness of the right insula explained differences in HRV as a function of depression severity (Koenig et al, 2018). Importantly, healthy controls and adolescents with MDD did not differ in the right insula cortical thickness.…”

“…Differences in the Association between Heart Rate Variability and Cortical Thickness of Regions of Interest in the Prefrontal Cortex in Depressed and Non‐Depressed Adolescents; illustrations done using cerebroViz in R (Bahl et al, 2017); Note data on cortical thickness based on Desikan‐Killiany atlas; translation of regions as followed: dorsolateral prefrontal cortex (DFC): rostral middle frontal gyrus; orbital frontal cortex (OFC): lateral orbitofrontal cortex; ventrolateral prefrontal cortex (VFC): pars orbitalis; color bar: indicates the strength and direction of correlation (Pearson correlation coefficient); data taken from (Koenig et al, 2018)…”