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

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.