Bipolar disorder and major depressive disorder (MDD) patients have differences in amygdala and orbitomedial prefrontal cortex (OMPFC) effective connectivity (EC) in response to happy faces, say researchers.

Bipolar depression is the most common presentation of bipolar disorder and often leads to a misdiagnosis of MDD. However, as emotional dysregulation is a central feature of bipolar disorder, neural dysfunction in systems supporting emotional regulation may help to discriminate the two groups.

To investigate further, Mary Phillips, from the University of Pittsburgh in Pennsylvania, USA, and colleagues studied 15 bipolar depressed and 16 MDD patients matched for age, age of illness onset, illness duration, and depression severity, and 16 age- and gender-matched healthy controls.

The participants were administered two event-related paradigms labeling the emotional intensity of happy and sad faces, respectively, during which OMPFC and amygdala blood oxygen level dependent signals were measured. Dynamic causal modeling was then used to examine significant among-group alterations in EC between right- and left-sided neural regions.

There were no differences among the groups in the labeling of emotional faces in either experiment, with no significant differences between the two depressed groups, the team notes in the journal Biological Psychiatry.

Compared with controls, both bipolar disorder and MDD patients had significantly reduced left-sided top-down OMPFC-amygdala EC during the happy experiment. EC values were positive for controls, close to zero for bipolar disorder patients, and negative for MDD patients.

Whereas bipolar disorder patients had significantly reduced right-sided bottom-up OMPFC-amygdala EC in response to the happy experiment, there were no significant differences between MDD patients and controls. EC values were positive for controls and MDD patients but negative for bipolar disorder patients.

The results also showed that, compared with controls, both MDD and bipolar disorder patients had significantly reduced left-sided top-down OMPFC-amygdala EC during the sad experiment.

“We show that bipolar depression and major depression are associated with different patterns of abnormal functional integration between different regions in neural systems supporting emotion regulation, in both hemispheres during happy emotion processing,” the team writes.

“This finding in turn suggests that different pathophysiological mechanisms might underlie these two types of depression and is a promising step forward toward identifying biological markers to distinguish between these different illnesses.”

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