The Suprachiasmatic Nucleus-Habenula Axis: A Circadian Mechanism for Suicide Risk and Mood Dysregulation

📖 Top 20% JournalJan 9, 2026Behavioural brain research

A Daily Rhythm Pathway Between the Body Clock and Emotion System That May Influence Suicide Risk and Mood Problems

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Suicidal behavior may peak during late-night and pre-dawn hours, indicating a circadian vulnerability.

The suprachiasmatic nucleus (SCN) interacts with the habenula to influence the timing of suicidality risk.
Disruption of the SCN's alignment with the habenula can lead to increased habenular activity at inappropriate times, heightening feelings of hopelessness.
Both the SCN and habenula express core clock genes and exhibit rhythmic activity that affects related brain circuits.
Misalignment can cause exaggerated fear responses and reduced prefrontal control, forming a circuit of fear and hopelessness.
This model suggests a circadian 'vulnerability window' for suicidality, aligning with epidemiological data.
Predictions include phase-specific peaks in suicidal thoughts and potential new strategies for prevention, such as chronotherapy.

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Suicidal behavior exhibits a striking circadian pattern, with risk clustering in the late-night and pre-dawn hours. Traditional models have attributed this vulnerability to sleep loss or psychosocial factors, yet such explanations fail to capture the precision of its timing. Here, we propose a novel framework in which the suprachiasmatic nucleus (SCN), the brain's master circadian clock, interacts with the habenula to generate temporally gated vulnerability to suicidality. The SCN normally entrains habenular excitability, aligning aversive bias with adaptive phases of the day. Disruption of this alignment results in habenular hyperactivity at inappropriate circadian phases, amplifying hopelessness, reward insensitivity, and negative prediction error processing. Anatomical and molecular evidence supports this axis: both regions express core clock genes (e.g., Bmal1, Per2) and exhibit rhythmic activity influencing downstream monoaminergic circuits. When misaligned, the amygdala further exaggerates fear responses while prefrontal cortical control is diminished, creating a triadic circuit of fear, hopelessness, and impaired regulation. This convergence generates a circadian "suicidal vulnerability window," consistent with epidemiological data. Our framework yields testable predictions, including phase-specific peaks in ideation, time-dependent treatment responses, and neuroimaging signatures of SCN-habenula coupling. Clinically, it reframes suicidality as a temporal disorder of affective circuits, suggesting new avenues for prevention: chronotherapy, phase-specific pharmacology, and biomarker-guided risk stratification. By integrating circadian neuroscience with psychiatry, the SCN-habenula model provides a mechanistic basis for the temporal dynamics of suicide risk and offers a foundation for precision-timed interventions.

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