Habenula volume increases with disease severity in unmedicated major depressive disorder as revealed by 7T MRI

Abstract

The habenula is a paired epithalamic structure involved in the pathogenesis of major depressive disorder (MDD). Evidence comes from its impact on the regulation of serotonergic and dopaminergic neurons, the role in emotional processing and studies on animal models of depression. The present study investigated habenula volumes in 20 unmedicated and 20 medicated MDD patients and 20 healthy controls for the first time by applying a triplanar segmentation algorithm on 7 Tesla magnetic resonance (MR) whole-brain T1 maps. The hypothesis of a right-side decrease of habenula volumes in the MDD patients was tested, and the relationship between volumetric abnormalities and disease severity was exploratively investigated. Absolute and relative total and hemispheric habenula volumes did not differ significantly between the three groups. In the patients with short duration of disease for which medication effects could be ruled out, significant correlations were found between bilateral habenula volumes and HAMD-17- and BDI-II-related severities. In the medicated patients, this positive relationship disappeared. Our findings suggest an involvement of habenula pathology in the beginning of MDD, while general effects independent of severity or stage of disease did not occur. Our findings warrant future combined tractographic and functional investigation using ultra-high-resolution in vivo MR imaging.

Reproducibility of myelin content‐based human habenula segmentation at 3 Tesla

“…The 7T UNI image and T1 map from MP2RAGE showed much higher habenula contrast than the 3T myelin‐sensitive images (Figure ), as has been previously suggested by others (Strotmann et al, ; Schmidt et al, ). We chose to use UNI image for our manual segmentation because of its similar contrast to T1w images (i.e., habenula as hyperintense).…”

“…Similar to the habenula volume differences between our intra‐site 3T and 7T comparison data of the same subjects, group level mean habenula volumes reported in the literature are variable. The mean habenula volumes measured by manual contrast‐based segmentation at 3T were 18.8/16.4 mm 3 (Savitz et al, ), 19.5/17.9 mm 3 (Savitz et al, ), left/right habenula respectively, and 43.0 mm 3 (Carceller‐Sindreu et al, ), bilateral, while those from 7T T1 map were 17.6/17.3 mm 3 (Schmidt et al, ), left/right habenula respectively in healthy controls. Using the geometric segmentation (i.e., Lawson's method), the habenula volumes from 3T were 27.9/28.0 mm 3 (Hétu et al, ), 28.3/28.7 mm 3 (Furman & Gotlib, ), 29.4/29.3 mm 3 (Lawson et al, ), left/right habenula respectively, and 22.3 mm 3 (Lawson et al, ) per hemisphere, while those from 7T (0.7 mm isotropic resolution MPRAGE) were 18.8/14.9 mm 3 (Torrisi et al, ), left/right habenula respectively.…”

“…Segmentation of the human habenula in in vivo neuroimaging is challenging due to its small size (37.2/34.2 mm 3 (Ahumada‐Galleguillos et al, ) or 30.9/33.2 mm 3 (Ranft et al, ) for left/right habenula, respectively from postmortem histology in deceased subjects without reported cerebral illness or neuropathy) and its low anatomical contrast to the neighboring dorsomedial thalamus. A majority of previous in vivo human habenula volumetric studies have used manual contrast‐based (Carceller‐Sindreu et al, ; Savitz et al, ; Savitz et al, ) or geometric segmentation (Lawson, Drevets, & Roiser, ) on T1‐weighted (T1w) 3T MRI, while more recently, manual contrast‐based segmentation of the habenula from ultra‐high field (7T) T1 maps has also been reported (Schmidt et al, ).…”

Translating the Habenula—From Rodents to Humans

“…In this study, major brain regions supporting the diagnosis classification were caudate, insula and Hb. Finally, a 7 T MRI study linked the increase of Hb volumes with disease severity in unmedicated major depressive patients, but not in medicated individuals, further supporting that changes in Hb volumes are linked to disease development (45). Of note is that volumetric changes of Hb have not been reported in animals to date, therefore mechanisms underlying this phenomenon have not been studied yet.…”

For Value or for Worth? Part 2: A Neuroeconomical Thought-Action-Mood-Space Modulated by (Un-)Certainty as Sign- or Goal-tracking

“…The LHb specifically act as indirect [155,156] strong inverse modulators [153] of the DA of the midbrain's SEEKING system [157], and the playfulness of STs is supported by the centrality of LHb for social play [158,157]. Conversely LHb and the medial habenula (MHb) are sensitive in the nondepressed to present [159] or future punishment [160] up to learned helplessness [161,162], produce vegetative costs of emotions [163], and shrink [164,165] especially in bipolar depression. Drugs inhibiting LHb reverse resistant depression [166].…”