Evidence map›Paper›PMID 41654494›Full record

ReviewTranslational psychiatry2026

The Habenula's role in major depressive disorder: recent insights from preclinical and human studies.

Feiteng Lin, Kayleigh Casmey, Sierra A Codeluppi-Arrowsmith, Gustavo Turecki

Abstract readReview
In one paragraph

Review in Translational psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Reply to Tarchini et al.: Evidence for a GPR156 role in central stress responses in addition to its inner-ear function.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Feiteng LinDepartment of Human Genetics, McGill University, Montréal, Canada.
Kayleigh CasmeyIntegrated Program in Neuroscience, McGill University, Montréal, QC, Canada.ORCID http://orcid.org/0009-0007-0539-7624
Sierra A Codeluppi-ArrowsmithMcGill Group for Suicide Studies, Douglas Institute, Department of Psychiatry, McGill University, Montréal, QC, Canada.
Gustavo TureckiDepartment of Human Genetics, McGill University, Montréal, Canada. gustavo.turecki@mcgill.ca.ORCID http://orcid.org/0000-0003-4075-2736

Funding

2/2 Large-scale, single-cell characterization of molecular and cellular networks of mood regulation circuitry in major depressive disorderR56MH131818 · NIMH · CENTRE DE RECHERCHE DE L'HOPITAL DOUGLAS · PI TURECKI, GUSTAVO · 2023 to 2023
$505k
Canada Research Chairs (Chaires de recherche du Canada) Tier 1Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R56MH131818-01Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) ENP161427 (ERA-NET ERA PerMed)Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) FDN148374Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) PJT183903Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) PJT189993NIMH NIH HHS R56 MH131818
6 · The paper itself

Abstract

The habenula is a small epithalamic structure composed of two distinct subregions, the medial (MHb) and lateral (LHb) habenula. It serves as a critical hub for integrating fronto-limbic and brainstem signals to regulate motivation, mood, and reward processing. Therefore, it is unsurprising that dysfunction of the habenula has been implicated in several mood disorders including major depressive disorder (MDD), a debilitating mood disorder marked by low mood and feelings of hopelessness. This review synthesizes recent advances in understanding the habenula's neurocircuitry, molecular landscape, and role in MDD pathophysiology, while evaluating its potential as a therapeutic target. Specifically, emerging evidence highlights subregion-specific pathology. Indeed, in MDD and in animal models of depression, the MHb has been shown to exhibit marked downregulation of calcium-dependent activator protein for secretion 2 (CAPS2) and deficits in nicotinic acetylcholine receptor-mediated signaling. While in the LHb, dysregulated expression profiles of inward-rectifying potassium channel Kir4.1, the β isoform of calcium/calmodulin-dependent protein kinase II (CaMKIIβ), protein phosphatase 2 A (PP2A), and small nucleolar RNA SNORA69 have been found in animal models of depression and MDD postmortem studies. Structural imaging and postmortem neurohistological studies in MDD patients have further revealed habenular volume changes, reduced neuronal cell counts, diminished cell area, and abnormal functional connectivity. As research unravels the habenula's complexities, its potential in treating mood disorders grows increasingly salient, offering new avenues for intervention in mental health.

Indexed as

HabenulaMajor Depressive DisorderAnimalsDisease Models, AnimalHumans

Identifiers

PMID41654494
PMCPMC12923909

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.