Rhythms of mood: Bidirectional regulation of molecular clocks and neurotransmission in affective disorders.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing preclinical and clinical mechanistic evidence
PubMed 42019704 · doi:10.1016/j.neubiorev.2026.106700
What was done
This review synthesized findings from animal models and clinical research regarding the bidirectional interactions between molecular circadian clocks and major neurotransmitter systems (monoamines including dopamine, serotonin, and norepinephrine, as well as glutamate and GABA) in major depressive disorder and bipolar disorder. It examined regulation between the central pacemaker (suprachiasmatic nucleus), semi-autonomous local clocks in limbic regions (prefrontal cortex, hippocampus, ventral tegmental area, nucleus accumbens), and neural networks mediating reward, stress, and synaptic plasticity.
What was found
The abstract reports no quantitative data or effect sizes. It describes a bidirectional mechanism where core clock genes regulate neurotransmitter systems governing mood and stress responses, while neurotransmitter signaling feeds back to entrain or disrupt local brain molecular clocks, leading to regional rhythm decoupling under stress.
Why it matters
The synthesis provides a mechanistic framework linking biological rhythm disruption to neurochemical dysregulation in affective disorders, supporting the rationale for circadian-targeted psychiatric interventions and precision chronotherapies.
Limits
The paper is a narrative review rather than a systematic review or meta-analysis, with no study selection criteria, sample sizes, or quantitative metrics reported in the abstract. Much of the detailed mechanistic circuitry relies on animal models, which may not fully translate to human mood disorders.
Cited by
- supports Almost every neurotransmitter, its receptor, or its recycling system exhibits a circadian rhythm.