Depression vulnerability involves brain activity and connectivity changes consistent with cholinergic deviancy

TL;DR

The study finds that brain activity and connectivity changes linked to acetylcholine may indicate a vulnerability to depression, even in those without a history of the disorder.

Contribution

Identifies cholinergic-related neural changes as a vulnerability marker for depression in both patients and their family members.

Findings

Shared fMRI markers in dorsal attention and visual areas between depression patients and family members.

Altered functional connectivity involving the lingual gyrus and lateral occipital complex in those at risk.

Changes suggest acetylcholine's role in sensory processing deficits before depression onset.

Abstract

•Depression vulnerability markers are shared by patients and their family members.•fMRI markers show changed dorsal attention activity during face perception.•Changes are consistent with acetylcholine-mediated moderation of top-down influences.•These changes are seen in family members with no own history of depression.•Vulnerability for depression involves general changes in neural processing of events.

Depression vulnerability markers are shared by patients and their family members.

fMRI markers show changed dorsal attention activity during face perception.

Changes are consistent with acetylcholine-mediated moderation of top-down influences.

These changes are seen in family members with no own history of depression.

Vulnerability for depression involves general changes in neural processing of events.

Behavioral and imaging studies suggests that emotional biases in the perception of faces associated with major depression disorder (MD) may be embedded within a broader sensory processing deficit. Increased cortical acetylcholine in MD suggest that this deficit may be related to abnormal attention modulation of sensory areas. It is not clear, however, whether these problems are a manifestation of the disease or whether they precede symptom onset. To investigate this, we applied functional magnetic resonance imaging (fMRI) to look for brain activity changes that participants with a family risk of MD (N = 30) shared with participant with MD (N = 28), compared to matched controls (N = 28). Participants were scanned while performing gender categorization of sad, happy, and neutral face pictures, as well as during a state of rest. Task-related activity changes, shared by participants at risk of and suffering from MD, were mostly seen in the posterior brain: increased activity in dorsal attention and visual association cortex, and decreased in lower visual areas. The changes did not differ between neutral faces and faces expressing an emotion. The at risk and MD participants additionally showed increased functional connectivity between the dorsal attention clusters and the lingual gyrus, and decreased connectivity with the lateral occipital complex (LOC). Lastly, they also had in common increased functional connectivity of magnocellular basal forebrain seeds with LOC and visual association cortex. These changes are consistent with an acetylcholine-mediated change in attention-guided sensory processing of all environmental events, which is discernable even before the first MD episode.

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