Domain‐specific impairment in cognitive control among remitted youth with a history of major depression

Abstract

Aim Impairment in neuropsychological functioning is common in major depressive disorder (MDD), but it is not clear to what degree these deficits are related to risk (e.g., trait), scar, burden, or state effects of MDD. The objective of this study was to use neuropsychological measures, with factor scores in verbal fluency, processing speed, attention, set-shifting, and cognitive control in a unique population of young, remitted, un-medicated, early course individuals with a history of MDD in hopes of identifying putative trait markers of MDD. Methods Youth aged 18-23 in remission from MDD (rMDD; n = 62) and healthy controls (HC; n = 43) were assessed with neuropsychological tests at two time points. These were from four domains of executive functioning, consistent with previous literature as impaired in MDD; verbal fluency and processing speed, conceptual reasoning and set-shifting, processing speed with interference resolution, and cognitive control. Results rMDD youth performed comparably to healthy controls on verbal fluency and processing speed, processing speed with interference resolution, and conceptual reasoning and set-shifting, reliably over time. Individuals with rMDD demonstrated relative decrements in cognitive control at Time 1, with greater stability than HC participants. Conclusion MDD may be characterized by regulatory difficulties that do not pertain specifically to active mood state or fluctuations in symptoms. Deficient cognitive control may represent a trait vulnerability or early course scar of MDD that may prove a viable target for secondary prevention or early remediation

Attenuated intrinsic connectivity within cognitive control network among individuals with remitted depression: Temporal stability and association with negative cognitive styles

“…This could suggest that the attenuated connectivity within the CCN detected in individuals with rMDD in our study is not simply a result of having a CCN that has different boundaries than those identified in prior studies. Our model of emotion regulation in MDD hypothesizes that some individuals have weaker capacity for cognitive control of emotion even in periods of relative wellness (Peters et al, 2015;Langenecker et al, 2014); although this study did not involve an emotion regulation task, the strength of the CCN at rest was attenuated in rMDD and was associated with cognitive factors involved in maladaptive emotion regulation. A lack of CCN coherence might interfere with the ability to exert top-down control over limbic activity to inhibit perseverative thinking states such as rumination (e.g., De Raedt and Koster, 2010;Joormann, 2010;Phillips et al, 2008;Roberts et al, 2013).…”

“…Consistent with this possibility, one study found attenuated connectivity within the CCN among adolescent girls at high risk due to having a parental history of depression, although this study did not evaluate cognitive vulnerability features (Clasen et al, 2014). Given that aberrant CCN functioning may underlie cognitive factors that are known to confer risk for MDD onset or relapse (e.g., Abela and Hankin, 2011;Alloy et al, 2006;Langenecker et al, 2007aLangenecker et al, , 2014Stange et al, 2014Stange et al, , 2016; for a review, see Alloy et al, 2016), longitudinal clinical staging studies are needed to determine whether deficits in CCN connectivity confer similar risk, may represent an early scar of illness, or a combination thereof (Grierson et al, 2016;Peters et al, 2015). To this end, recent studies have demonstrated that greater CCN task-based activation (including dorsolateral prefrontal cortex and inferior parietal lobule) during inhibitory control predicted a greater likelihood of responding to antidepressant treatment for MDD (Gyurak et al, 2016;Langenecker et al, 2007a).…”

“…The task yields two variables that were used for analysis: No-Go percent correct inhibition (PGNG-PCI; task-related fMRI results to be reported elsewhere), and inhibitory processing speed on correct trials (Reaction Time; PGNG-RT). The PGNG has demonstrated good construct validity and retest reliability in healthy and depressed samples (Langenecker et al, 2007b,c; Votruba & Langenecker, 2013, Peters et al, 2015). …”

“…Indeed, prior work has suggested that connectivity within the CCN may have utility as a biomarker for individual differences in cognitive control performance, although this has not been pursued in MDD (e.g., Niendam et al, 2012;Seeley et al, 2007). Our model for understanding dysfunctional emotion regulation in MDD posits that many individuals with MDD have weaker cognitive control functioning (regulation), and that this weakness remains even in periods of relative wellness (Peters et al, 2015;Hassleback et al, 2011). It is possible that resting-state connectivity of intrinsic connectivity networks can elucidate this phenomenon.…”

“…Given that intrinsic functional networks bias information processing in the brain (Menon, 2011;Sadaghiani et al, 2010), aberrant CCN functioning may underlie several cognitive factors that confer risk for MDD onset or relapse (e.g., Disner et al, 2011;Marchetti et al, 2012). For example, deficits in inhibitory controlthe ability to voluntarily regulate prepotent responses-are related to attenuated activity in the CCN, particularly the dlPFC, are stable and reliable over time, and confer risk for depressive relapse (Langenecker et al, 2006(Langenecker et al, , 2007aPeters et al, 2015;Wagner et al, 2006).…”