A resting‐state study of volumetric and functional connectivity of the habenular nucleus in treatment‐resistant depression patients

Abstract

Objective To investigate the volumetric and functional connectivity of the habenular nucleus in treatment‐resistant depression (TRD) patients using the resting‐state functional magnetic resonance imaging (rs‐fMRI) approach. Methods A total of 15 TRD patients, who visited the Mental Health Institute of the First Hospital Affiliated with Jilin University between August 2014 and March 2015, along with 15 normal subjects, were enrolled into this study for structural and functional imaging. Functional connectivity analysis was performed using bilateral habenular nuclei as the region of interest in contrast to whole‐brain voxels. Results No significant difference of absolute volume was found in bilateral habenular nuclei between TRD patients and healthy controls, or after controlling for individual total intracranial volume. However, functional connectivity analysis showed increased connectivity between the right habenular nucleus with the medial superior frontal gyrus, anterior cingulate cortex and medial orbitofrontal gyrus, and decreased connectivity with the corpus callosum in the TRD group. For the left habenular nucleus seed, the brain region with increased functional connectivity in the inferior temporal gyrus and decreased functional connectivity in the insular was found in the TRD patients. Conclusion Abnormal functional connectivity was present between the habenular nucleus and the default mode network in TRD patients. Dysfunction in habenular nucleus‐related circuitry for processing negative emotion might form the pathological basis for TRD. Significant asymmetric functional connectivity was also found between bilateral habenular nuclei in TRD patients. Such asymmetry suggests potentially divergent strategy for intervention on bilateral habenular nucleus regions in the future management of depression.

Functional connectivity between the amygdala and subgenual cingulate gyrus predicts the antidepressant effects of ketamine in patients with treatment‐resistant depression

“…7,35,43 These findings have been extended to the pathophysiology of TRD. 10,[44][45][46] However, fewer studies have reported a relationship between changes in RSFC and treatment response heterogeneity in TRD patients. 18,47,48 In this study, the seed-based exploratory analysis at baseline revealed a cluster that was associated with treatment response to ketamine within the AN, but not the DMN.…”

“… 7 , 35 , 43 These findings have been extended to the pathophysiology of TRD. 10 , 44 , 45 , 46 However, fewer studies have reported a relationship between changes in RSFC and treatment response heterogeneity in TRD patients. 18 , 47 , 48 …”

Abnormal habenula functional connectivity characterizes treatment-resistant depression

“…Previous fMRI studies indicate that abnormal circuitry underlying TRD may involve the affective, salience, auditory, visual networks, and the language processing cortex ( He et al, 2016 ). Recent studies have shown, more specifically, abnormal functional connectivity (FC) in the habenular nucleus ( Amiri et al, 2021 ), especially with the default mode network (DMN) ( Luan et al, 2019 ) in TRD patients. This is very interesting given the putative functions of the habenula.…”

Left-right asymmetric and smaller right habenula volume in major depressive disorder on high-resolution 7-T magnetic resonance imaging

“…It is an epithalamic structure and anatomical hub located at the center of the dorsal diencephalic conduction system, a pathway linking the forebrain to midbrain regions [9]. The Hb is considered to be related to punishment and motor activity during reward processes and the adaptive response to stress [10,11], and based on previous experiments with animals, it is hypothesized to play an important role in controlling emotions; notably, the overactivation of the Hb is reported to be associated with depression [12][13][14]. Consistent with the monoamine hypothesis of MDD, the Hb is thought to regulate the activity of ascending monoaminergic projections from the brainstem [15], and increased metabolism of the Hb has been observed in animal models of stress and depression [16].…”