The neural basis of hot and cold cognition in depressed patients, unaffected relatives, and low-risk healthy controls: An fMRI investigation

Pilling S,Lally N,Nord Cl,Roiser Jp,Limbachya T,Halahakoon Dc

doi:10.1016/j.jad.2020.05.022

Abstract

BackgroundModern cognitive neuropsychological models of depression posit that negatively biased emotional (“hot”) processing confers risk for depression, while preserved executive function (“cold”) cognition promotes resilience. MethodsWe compared neural responses during hot and cold cognitive tasks in 99 individuals: those at familial risk for depression (N = 30 unaffected first-degree relatives of depressed individuals) and those currently experiencing a major depressive episode (N = 39 unmedicated depressed patients) with low-risk healthy controls (N = 30). Primary analyses assessed neural activation on two functional magnetic resonance imaging tasks previously associated with depression: dorsolateral prefrontal cortex (DLPFC) responsivity during the n-back working memory task; and amygdala and subgenual anterior cingulate cortex (sgACC) responsivity during incidental emotional face processing. ResultsDepressed patients exhibited significantly attenuated working memory-related DLPFC activation, compared to low-risk controls and unaffected relatives; unaffected relatives did not differ from low-risk controls. We did not observe a complementary pattern during emotion processing. However, we found preliminary support that greater DLPFC activation was associated with lower amygdala response during emotion processing. LimitationsThese findings require confirmation in a longitudinal study to observe each individual's risk of developing depression; without this, we cannot identify the true risk level of the first-degree relative or low-risk control group. ConclusionsThese findings have implications for understanding the neural mechanisms of risk and resilience in depression: they are consistent with the suggestion that preserved executive function might confer resilience to developing depression in first-degree relatives of depressed patients.

Highlights

History plays an important role in the development and maintenance of major depressive disorder (MDD): first-degree relatives of patients with MDD have a two-to-fourfold increased risk of developing MDD (Weissman et al, 1993), and MDD tends to onset earlier, and recur more frequently in patients with a family history (Gotlib et al, 2014; Hollon et al, 2006)
We found no associations between dorsolateral prefrontal cortex (DLPFC) activation and questionnaire measures of symptoms in depressed patients (BDI: r=−0.114, p = 0.491; Snaith-Hamilton Pleasure Scale (SHAPS): r=−0.027, p = 0.869; Beck Anxiety Inventory (BAI): r = 0.082, p = 0.619; HAMD r=−0.114, p = 0.491)
We found that unaffected first-degree relatives showed indistinguishable DLPFC activation from low-risk controls during working memory, while depressed patients showed hypoactivation in the DLPFC, compared with low-risk controls

Summary

Introduction

History plays an important role in the development and maintenance of major depressive disorder (MDD): first-degree relatives of patients with MDD have a two-to-fourfold increased risk of developing MDD (Weissman et al, 1993), and MDD tends to onset earlier, and recur more frequently in patients with a family history (Gotlib et al, 2014; Hollon et al, 2006). There is an extensive literature describing differences in the neural basis of “hot” and “cold” cognition in patients with MDD (Disner et al, 2011; Graham et al, 2013; Hamilton et al, 2012; Hamilton and Gotlib, 2008; MacNamara et al, 2017; Schulze et al, 2019; Wang et al, 2015) This has been measured primarily in three ways: using “hot” emotion processing tasks; using “cold” executive function tasks; and using tasks that address the relationship between prefrontal and limbic regions in depression within the same task (note that even when measured independently, it is difficult to fully separate ‘hot’ and ‘cold’ tasks, since even in many cold cognitive tasks, providing feedback on the task might elicit group differences that are driven by the ‘hot’ processing of feedback rather than the ‘cold’ cognitions themselves). Conclusions: These findings have implications for understanding the neural mechanisms of risk and resilience in depression: they are consistent with the suggestion that preserved executive function might confer resilience to developing depression in first-degree relatives of depressed patients

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Results

Discussion

Conclusion