Unmasking Disease-Specific Cerebral Blood Flow Abnormalities: Mood Challenge in Patients With Remitted Unipolar Depression

OBJECTIVE: Remitted major depressive disorder is a vulnerable clinical state, suggesting persistence of an underlying disease diathesis between episodes. To investigate neural correlates of such risk and to identify potential depression trait markers, euthymic unipolar patients in remission, acutely depressed patients, and never-depressed volunteers were studied before and after transient sad mood challenge. METHOD: Common and differential changes in regional blood flow among the groups relative to the baseline state were examined with [¹⁵O]H₂O positron emission tomography after provocation of sadness with autobiographical memory scripts. RESULTS: Mood provocation in both depressed groups resulted in regional cerebral blood flow (rCBF) decreases in medial orbitofrontal cortex Brodmann’s area 10/11, which were absent in the healthy group. In the remitted group, mood provocation produced a unique rCBF decrease in pregenual anterior cingulate 24a. The main effects in healthy subjects, an rCBF increase in subgenual cingulate Brodmann’s area 25 and a decrease in right prefrontal cortex Brodmann’s area 9, were not present in the depressed groups. CONCLUSIONS: Mood challenge in unipolar euthymic patients in full remission unmasks an apparent depression trait marker. The pattern of acute CBF changes is distinct from that seen in euthymic healthy volunteers and mirrors the untreated depressed state seen during a major depressive episode and the pattern of change seen in depressed patients. These findings suggest that disease-specific modifications of pathways mediating transient mood changes are present in unipolar depression independent of clinical illness status. These findings have implications for understanding the vulnerability of remitted patients for illness relapse.