Changes in brain function during negative emotion processing in the long-term course of depression

Abstract

Background Relapses in major depression are frequent and are associated with a high burden of disease. Although short-term studies suggest a normalisation of depression-associated brain functional alterations directly after treatment, long-term investigations are sparse. Aims To examine brain function during negative emotion processing in association with course of illness over a 2-year span. Method In this prospective case–control study, 72 in-patients with current depression and 42 healthy controls were investigated during a negative emotional face processing paradigm, at baseline and after 2 years. According to their course of illness during the study interval, patients were divided into subgroups (n = 25 no-relapse, n = 47 relapse). The differential changes in brain activity were investigated by a group × time analysis of covariance for the amygdala, hippocampus, insula and at whole-brain level. Results A significant relapse × time interaction emerged within the amygdala (PTFCE-FWE = 0.011), insula (PTFCE-FWE = 0.001) and at the whole-brain level mainly in the temporal and prefrontal cortex (PTFCE-FWE = 0.027), resulting from activity increases within the no-relapse group, whereas in the relapse group, activity decreased during the study interval. At baseline, the no-relapse group showed amygdala, hippocampus and insula hypoactivity compared with healthy controls and the relapse group. Conclusions This study reveals course of illness-associated activity changes in emotion processing areas. Patients in full remission show a normalisation of their baseline hypo-responsiveness to the activation level of healthy controls after 2 years. Brain function during emotion processing could further serve as a potential predictive marker for future relapse.

Brain structural correlates of recurrence following the first episode in patients with major depressive disorder

“…In conclusion, this study provides preliminary evidence that recurrence at an early stage of MDD can lead to detrimental effects in brain regions that are involved in emotion perception and regulation [ 40 , 44 , 45 , 62 , 63 ]. Although alterations of the DLPFC, hippocampus and insula were not identified as neural precursors of recurrence at this initial illness stage, the DLPFC and insula seem particularly sensitive to neurotoxic effects of recurrence over time and may therefore already play a crucial role in the early progression of MDD.…”

Persistence of amygdala hyperactivity to subliminal negative emotion processing in the long-term course of depression

“…The final study sample comprised n = 57 patients with MDD and n = 37 HC. As described in our previous works [ 19 , 29 , 30 ], we divided the patient group into two subgroups, depending on their course if illness from baseline to follow-up (according to SCID-I criteria): Patients who were in ongoing depression at follow-up or experienced at least one depressive relapse between baseline and follow-up ( MDD relapse -group; n = 37), and patients who were in full remission at follow-up without any further depressive episode after baseline ( MDD no-relapse -group; n = 20). Demographic and clinical details of the sample are included in Table 1 .…”

“…Details on comorbidities can be found in Supplementary Table 1 . There was an overlap of n = 87 participants with our previous study investigating long-term changes in brain function during conscious emotion processing, employing a different, unrelated fMRI paradigm [ 19 ].…”

“…Acquisition and preprocessing of fMRI data followed previously published protocols [ 19 , 32 , 33 ].…”

“…A key question in understanding vulnerability to depression is whether this abnormality in automatic negative processing is an enduring neurofunctional “trait” of depression or whether it is rather associated with the depressive state itself. Long-term neuroimaging studies have only examined changes in controlled stages of emotion processing, and suggest a normalization of activity in limbic regions in case of remission [ 19 – 21 ]. Regarding automatic emotion processing, there are no prospective neuroimaging studies examining the course of depression over periods longer than 8 weeks.…”