Reduced default mode network suppression during a working memory task in remitted major depression

Abstract

Insufficient default mode network (DMN) suppression was linked to increased rumination in symptomatic Major Depressive Disorder (MDD). Since rumination is known to predict relapse and a more severe course of MDD, we hypothesized that similar DMN alterations might also exist during full remission of MDD (rMDD), a condition known to be associated with increased relapse rates specifically in patients with adolescent onset. Within a cross-sectional functional magnetic resonance imaging study activation and functional connectivity (FC) were investigated in 120 adults comprising 78 drug-free rMDD patients with adolescent- (n = 42) and adult-onset (n = 36) as well as 42 healthy controls (HC), while performing the n-back task. Compared to HC, rMDD patients showed diminished DMN deactivation with strongest differences in the anterior-medial prefrontal cortex (amPFC), which was further linked to increased rumination response style. On a brain systems level, rMDD patients showed an increased FC between the amPFC and the dorsolateral prefrontal cortex, which constitutes a key region of the antagonistic working-memory network. Both whole-brain analyses revealed significant differences between adolescent-onset rMDD patients and HC, while adult-onset rMDD patients showed no significant effects. Results of this study demonstrate that reduced DMN suppression exists even after full recovery of depressive symptoms, which appears to be specifically pronounced in adolescent-onset MDD patients. Our results encourage the investigation of DMN suppression as a putative predictor of relapse in clinical trials, which might eventually lead to important implications for antidepressant maintenance treatment.

Increased Default Mode Network Connectivity in Individuals at High Familial Risk for Depression

“…Functional MRI studies, for example, indicate that in patients with depressive disorders, the DMN is hyperactive during periods self-referential thought (Sheline et al, 2009), and this increased activity does not abate during attention-demanding tasks (Anticevic et al, 2012;Wagner et al, 2013). Individuals with remitted depression also demonstrate this failure to suppress DMN activity during attention-demanding tasks (Marchetti et al, 2012;Bartova et al, 2015). Similarly, when individuals with or without depression engage in self-referential thinking, DMN connectivity increases; conversely, as individuals shift from self-referential to externally focused thoughts, DMN Figure 2 Path modeling of default mode network connectivity.…”

Precision psychiatry: a neural circuit taxonomy for depression and anxiety

“…18 Problems with selective inhibition in depression could also be suggested by problems suppressing default mode rumination, and a profile of positive correlation (rather than anticorrelation) between dorsal prefrontal cognitive control regions and posterior cingulate default mode regions. 25,64 …”

Decreased Fronto-Parietal and Increased Default Mode Network Activation is Associated with Subtle Cognitive Deficits in Elderly Controls

“…The DMN involves bilateral and symmetrical cortical areas in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices [5]. It is usually more active during rest and may change its connectivity during WM tasks [6-8]. The FPN comprises fronto–parietal regions such as the superior, middle and inferior frontal gyri in addition to the inferior parietal lobules It is typically activated during executive functions and its integrity is critical for the successful performance of WM tasks [9, 10].…”