Affect-Regulation Related Emergent Brain Network Properties Differentiate Depressed Bipolar Disorder from Major Depression and Track Risk for Bipolar

Published:October 09, 2021DOI:



      Individuals with/at risk for Bipolar Disorder (BD) often present initially for the treatment of depressive symptoms. Unfortunately, pharmacological treatments for Major Depressive Disorder (MDD) can be iatrogenic, precipitating mania which may not have otherwise occurred. Current diagnostic procedures rely solely on self-reported/observable symptoms, and thus alternative data sources, like brain network properties, are needed to supplement current self-report/observation-based indices of risk for mania.


      Brain connectivity during affect maintenance/regulation was examined in a large (N=249), medication-free sample of currently depressed BD (n=50) and MDD (n=116) patients and healthy controls (n=83). BD risk was categorized in a subset of MDD patients. We used graph theory to identify emergent network properties that differentiated between (i) BD and MDD and (ii) MDD patients at high and low risk for BD.


      BD and MDD differed in the (i) extent to which rostral anterior cingulate was embedded in the local network, (ii) amount of influence hippocampus exerted over global network communication, and (iii) clarity of orbitofrontal cortex communication. MDD patients at high BD risk showed a pattern of local network clustering around right amygdala that was similar to healthy controls, whereas MDD at low risk for BD deviated from this pattern.


      BD and MDD differed in emergent network mechanisms subserving affect regulation, and amygdala properties tracked BD risk in MDD patients. If replicated, present findings may be combined with other markers to assess the presence of BD/BD-risk in individuals presenting with depressive symptoms in order to prevent the use of iatrogenic treatments.


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