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Influence of Familial Risk for Depression on Cortico-Limbic Connectivity During Implicit Emotional Processing.

ABSTRACT: Imbalances in cortico-limbic activity and functional connectivity (FC) supposedly underlie biased emotional processing and present putative intermediate phenotypes (IPs) for major depressive disorder (MDD). To prove the validity of these IPs, we assessed them in familial risk. In 70 healthy first-degree relatives of MDD patients and 70 controls, brain activity and seed-based amygdala FC were assessed during an implicit emotional processing task for fMRI containing angry and fearful faces. Using the generalized psychophysiological interaction approach, amygdala FC was assessed (a) across conditions to provide comparable data to previous studies and (b) compared between conditions to elucidate its implications for emotional processing. Associations of amygdala FC with self-reported negative affect were explored post hoc. Groups did not differ in brain activation. In relatives, amygdala FC across conditions was decreased with superior and medial frontal gyrus (SFG, MFG) and increased with subgenual and perigenual anterior cingulate cortex (sgACC, pgACC). NA was inversely correlated with amygdala FC with MFG, pgACC and their interaction in relatives. Relatives showed aberrant condition-dependent modulations of amygdala FC with visual cortex, thalamus and orbitofrontal cortex. Our results do not support imbalanced cortico-limbic activity as IP for MDD. Diminished amygdala-dorsomedial prefrontal FC in relatives might indicate insufficient regulatory capacity, which appears to be compensated by ventromedial prefrontal regions. Differential task-dependent modulations of amygdala FC are discussed as a stronger involvement of automatic instead of voluntary emotional processing pathways. Reliability and etiological implications of these results should be investigated in future studies including longitudinal designs and patient-risk-control comparisons.

SUBMITTER: Wackerhagen C

PROVIDER: S-EPMC5518910 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Influence of Familial Risk for Depression on Cortico-Limbic Connectivity During Implicit Emotional Processing.

Wackerhagen Carolin C Wüstenberg Torsten T Mohnke Sebastian S Erk Susanne S Veer Ilya M IM Kruschwitz Johann D JD Garbusow Maria M Romund Lydia L Otto Kristina K Schweiger Janina I JI Tost Heike H Heinz Andreas A Meyer-Lindenberg Andreas A Walter Henrik H Romanczuk-Seiferth Nina N

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20170315 8

Imbalances in cortico-limbic activity and functional connectivity (FC) supposedly underlie biased emotional processing and present putative intermediate phenotypes (IPs) for major depressive disorder (MDD). To prove the validity of these IPs, we assessed them in familial risk. In 70 healthy first-degree relatives of MDD patients and 70 controls, brain activity and seed-based amygdala FC were assessed during an implicit emotional processing task for fMRI containing angry and fearful faces. Using ...[more]

PMID: 28294134

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Project description:Major depressive disorder is a leading cause of disability and significant mortality, yet mechanistic understanding remains limited. Over the past decade evidence has accumulated from case-control studies that depressive illness is associated with blunted reward activation in the basal ganglia and other regions such as the medial prefrontal cortex. However it is unclear whether this finding can be replicated in a large number of subjects. The functional anatomy of the medial prefrontal cortex and basal ganglia has been extensively studied and the former has excitatory glutamatergic projections to the latter. Reduced effect of glutamatergic projections from the prefrontal cortex to the nucleus accumbens has been argued to underlie motivational disorders such as depression, and many prominent theories of major depressive disorder propose a role for abnormal cortico-limbic connectivity. However, it is unclear whether there is abnormal reward-linked effective connectivity between the medial prefrontal cortex and basal ganglia related to depression. While resting state connectivity abnormalities have been frequently reported in depression, it has not been possible to directly link these findings to reward-learning studies. Here, we tested two main hypotheses. First, mood symptoms are associated with blunted striatal reward prediction error signals in a large community-based sample of recovered and currently ill patients, similar to reports from a number of studies. Second, event-related directed medial prefrontal cortex to basal ganglia effective connectivity is abnormally increased or decreased related to the severity of mood symptoms. Using a Research Domain Criteria approach, data were acquired from a large community-based sample of subjects who participated in a probabilistic reward learning task during event-related functional MRI. Computational modelling of behaviour, model-free and model-based functional MRI, and effective connectivity dynamic causal modelling analyses were used to test hypotheses. Increased depressive symptom severity was related to decreased reward signals in areas which included the nucleus accumbens in 475 participants. Decreased reward-related effective connectivity from the medial prefrontal cortex to striatum was associated with increased depressive symptom severity in 165 participants. Decreased striatal activity may have been due to decreased cortical to striatal connectivity consistent with glutamatergic and cortical-limbic related theories of depression and resulted in reduced direct pathway basal ganglia output. Further study of basal ganglia pathophysiology is required to better understand these abnormalities in patients with depressive symptoms and syndromes.

Dataset Information

Influence of Familial Risk for Depression on Cortico-Limbic Connectivity During Implicit Emotional Processing.

Publications

Influence of Familial Risk for Depression on Cortico-Limbic Connectivity During Implicit Emotional Processing.

Similar Datasets

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