Differential neural processing of unpleasant sensory stimulation in patients with major depression

Abstract

An altered processing of negative salient stimuli has been suggested to play a central role in the pathophysiology of major depression (MD). Besides negative affective and social stimuli, physical pain as a subtype of negative sensory stimulation has been investigated in this context. However, the few neuroimaging studies on unpleasant sensory stimulation or pain processing in MD report heterogeneous findings. Here, we investigated 47 young females, 22 with MD and 25 healthy controls (HC) using fMRI (3.0 T). Four levels of increasingly unpleasant electrical stimulation were applied. Ratings of stimulus intensity were assessed by a visual analogue scale. fMRI-data were analyzed using a 2 × 4 ANOVA. Behavioral results revealed no group differences regarding accuracy of unpleasant stimulation level ratings and sensitivity to stimulation. Regarding neural activation related to increasing levels of unpleasant stimulation, we observed increasing activation of brain regions related to the pain and salient stimulus processing corresponding to increasingly unpleasant stimulation in controls. This modulation was significantly smaller in MD compared to controls, particularly in the dorsal anterior cingulate cortex, the somatosensory cortex, and the posterior insula. Overall, brain regions associated with the processing of unpleasant sensory stimulation, but also associated with the salience network, were highly reactive but less modulated in female patients with MD. These results support and extent findings on altered processing of salience and of negative sensory stimuli even of a non-painful quality in female patients with MD.

Neural correlates of co-occurring pain and depression: an activation-likelihood estimation (ALE) meta-analysis and systematic review

“…All six analyses found significant associations between depression and pain, two of which sampled patients clinically diagnosed with major depressive disorder [ 45 , 46 ]. Malejko et al [ 45 ] was the only task-fMRI study that identified the primary somatosensory cortex (S1) as negatively correlated in depression with induced pain; participants reported severe clinically diagnosed depression, but pain severity was unknown.…”

“…All six analyses found significant associations between depression and pain, two of which sampled patients clinically diagnosed with major depressive disorder [ 45 , 46 ]. Malejko et al [ 45 ] was the only task-fMRI study that identified the primary somatosensory cortex (S1) as negatively correlated in depression with induced pain; participants reported severe clinically diagnosed depression, but pain severity was unknown. Berna et al (2010) and Strigo et al (2008) identified hippocampus/amygdala using task-fMRI in participants with moderate pain and minimal to clinically significant depression (greater activity in depression/pain than in healthy controls), after adjusting ratings of induced pain.…”

Neural signature of error processing in major depression

“…As part of a broader research project with different experiments of which findings are reported elsewhere [ 38 , 39 ], we investigated a total of 33 young adult female participants aged 18–38 years. Of those, 16 patients were diagnosed with MD whereas 17 healthy participants (HC) served as control group with no current or lifetime psychiatric diagnosis.…”

An assessment of sensory sensitivity in women suffering from depression using transcutaneous electrical nerve stimulation

“…The above shows that depression and pain are often co-morbid and decrease the quality of life of many individuals worldwide. An exact understanding of the pathophysiology of chronic pain and depression and of why comorbidity of these two disorders is so common is still a matter for research ( Thompson et al, 2016 ; Nitzan et al, 2019 ; Malejko et al, 2021 ). However, although the biological mechanisms are still to be explained, it has been hypothesised that depression and pain may share the same descending tracts of the central nervous system, possibly involving serotonin, noradrenaline, and dopamine ( Pinheiro Campos et al., 2020 ; Thompson et al, 2016 ).…”