Abstract
Major depressive disorder (MDD) is characterized by altered intrinsic functional connectivity within (intra-iFC) intrinsic connectivity networks (ICNs), such as the Default Mode- (DMN), Salience- (SN) and Central Executive Network (CEN). It has been proposed that aberrant switching between DMN-mediated self-referential and CEN-mediated goal-directed cognitive processes might contribute to MDD, possibly explaining patients' difficulties to disengage the processing of self-focused, often negatively biased thoughts. Recently, it has been shown that the right anterior insula (rAI) within the SN is modulating DMN/CEN interactions. Since structural and functional alterations within the AI have been frequently reported in MDD, we hypothesized that aberrant intra-iFC in the SN's rAI is associated with both aberrant iFC between DMN and CEN (inter-iFC) and severity of symptoms in MDD. Twenty-five patients with MDD and 25 healthy controls were assessed using resting-state fMRI (rs-fMRI) and psychometric examination. High-model-order independent component analysis (ICA) of rs-fMRI data was performed to identify ICNs including DMN, SN, and CEN. Intra-iFC within and inter-iFC between distinct subsystems of the DMN, SN, and CEN were calculated, compared between groups and correlated with the severity of symptoms. Patients with MDD showed (1) decreased intra-iFC within the SN's rAI, (2) decreased inter-iFC between the DMN and CEN, and (3) increased inter-iFC between the SN and DMN. Moreover, decreased intra-iFC in the SN's rAI was associated with severity of symptoms and aberrant DMN/CEN interactions, with the latter losing significance after correction for multiple comparisons. Our results provide evidence for a relationship between aberrant intra-iFC in the salience network's rAI, aberrant DMN/CEN interactions and severity of symptoms, suggesting a link between aberrant salience mapping, abnormal coordination of DMN/CEN based cognitive processes and psychopathology in MDD.
Highlights
Major depressive disorder (MDD) is a severe mental disorder defined by the presence of at least one major depressive episode (MDE), which is primarily characterized by depressed mood, diminished interest, loss of energy, impaired cognition, and suicidal tendency (American Psychiatric Association, 2000)
Intra-iFC As previously described (Manoliu et al, 2013b), automated component selection, which was based on spatial templates representing subsystems of the Default Mode Network (DMN), SN, and Central Executive Network (CEN), revealed 7 components of interest for each participant [see Figure 1 for presentation of spatial templates according to Allen et al (2011)]: The SN was represented in one component (SN, corresponding with Allen-IC 55)
All selected components were spatially consistent across groups and matched previous results of SN, DMN, and CEN (Allen et al, 2011)
Summary
Major depressive disorder (MDD) is a severe mental disorder defined by the presence of at least one major depressive episode (MDE), which is primarily characterized by depressed mood, diminished interest, loss of energy, impaired cognition, and suicidal tendency (American Psychiatric Association, 2000). In MDD, increased activation in response to negative stimuli (Strigo et al, 2008) as well as aberrant iFC at rest [see Sliz and Hayley (2012) and Diener et al (2012) for extensive review] have been reported in the AI, possibly indicating heightened SN response selectively to negative stimuli Taken together, these findings suggest a reorganization of iFC within DMN, SN and CEN in MDD, potentially contributing to characteristic symptoms in MDD, such as rumination (DMN), emotional overreactivity (SN), and emotional disinhibition (CEN) (Hamilton et al, 2013)
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