Functional but not structural subgenual prefrontal cortex abnormalities in melancholia

Abstract

Major depression is a heterogeneous condition, and the search for neural correlates specific to clinically defined subtypes has been inconclusive. Theoretical considerations implicate frontostriatal, particularly subgenual prefrontal cortex (PFC), dysfunction in the pathophysiology of melancholia-a subtype of depression characterized by anhedonia-but no empirical evidence has been found yet for such a link. To test the hypothesis that melancholic, but not nonmelancholic depression, is associated with the subgenual PFC impairment, concurrent measurement of brain electrical (electroencephalogram, EEG) and metabolic (positron emission tomography, PET) activity were obtained in 38 unmedicated subjects with DSM-IV major depressive disorder (20 melancholic, 18 nonmelancholic subjects), and 18 comparison subjects. EEG data were analyzed with a tomographic source localization method that computed the cortical three-dimensional distribution of current density for standard frequency bands, allowing voxelwise correlations between the EEG and PET data. Voxel-based morphometry analyses of structural magnetic resonance imaging (MRI) data were performed to assess potential structural abnormalities in melancholia. Melancholia was associated with reduced activity in the subgenual PFC (Brodmann area 25), manifested by increased inhibitory delta activity (1.5-6.0 Hz) and decreased glucose metabolism, which themselves were inversely correlated. Following antidepressant treatment, depressed subjects with the largest reductions in depression severity showed the lowest post-treatment subgenual PFC delta activity. Analyses of structural MRI revealed no group differences in the subgenual PFC, but in melancholic subjects, a negative correlation between gray matter density and age emerged. Based on preclinical evidence, we suggest that subgenual PFC dysfunction in melancholia may be associated with blunted hedonic response and exaggerated stress responsiveness.

Amygdala Perfusion Is Predicted by Its Functional Connectivity with the Ventromedial Prefrontal Cortex and Negative Affect

“…The peaks of the clusters in B (4, 2, −7) and D (2, 4, −4) were localized to the posterior-most portion of the SGC (with both clusters extending into the hypothalamus) using two independent atlases (the Talairach and Tournoux Stereotaxic Atlas [46] and the Wake Forrest University (WFU) PickAtlas [47]; see Methods). Prior work further supports this localization; previously reported sites that have been localized to the SGC (BA25), as well as an architectonic mapping of BA25 [68], overlap with the two clusters reported here, with nearby peaks: 4, 2, −4 [69]; −2, 6, −6 [8]; −2, 8, −10 [70]; −3, 9, −6 [71]; −4, 9, −12 & 2, 11, −7 [72]; 0, 8, −16 [73]. BLA, basolateral amygdala; FC, functional connectivity; Hy, hypothalamus; SGC, subgenual cingulate gyrus; mPFC, medial prefrontal cortex.…”

It still hurts: altered endogenous opioid activity in the brain during social rejection and acceptance in major depressive disorder

“…In contrast, MDD patients showed MOR activation in the midline thalamus, which may impede sustained positive affect. MDD patients also did not show MOR deactivation in the sgACC, a region shown to be functionally associated with anhedonia 51,52 . Unexpectedly, MDD patients reported a greater increase in positive affect relative to baseline during acceptance compared to HCs, however this increase was short-lived (Fig.…”

Occipital sources of resting-state alpha rhythms are related to local gray matter density in subjects with amnesic mild cognitive impairment and Alzheimer's disease

“…These mapped ROIs masks were used to obtain GMD values of all voxels belonging to left and right occipital and temporal lobes from the original GM probability maps. Finally, GMD within the occipital lobe was obtained by averaging the GMD values of all voxels within that lobe (Pizzagalli et al, 2004). The same procedure was true for the temporal lobe.…”