Nitric Oxide Modulation in Affective Disorders
Summary
Nitric oxide (NO) is a gaseous signalling molecule that exerts multifaceted roles in the central nervous system, from regulating neurotransmitter release to shaping synaptic plasticity. Synthesised by distinct isoforms of nitric oxide synthase (NOS), NO influences intracellular cascades both via activation of soluble guanylyl cyclase and through direct post-translational modifications such as S-nitrosylation and nitration. In affective disorders, dysregulated NO signalling has been linked to maladaptive stress responses, impaired neuroplasticity and altered monoaminergic balance. Excessive or prolonged NO production may compromise the function of key molecular partners, including brain-derived neurotrophic factor (BDNF) receptors and N-methyl-D-aspartate (NMDA) channels, thereby contributing to cognitive deficits, mood instability and anxiety phenotypes. Conversely, modest modulation of NO synthesis can restore synaptic function and ameliorate emotional disturbances in preclinical models. This dual nature of NO underpins its emergence as both a biomarker of disease state and a potential target for novel therapeutics. Efforts to fine-tune NO availability—through selective NOS inhibitors, NO-donating compounds or pathway-specific modulators—aim to rebalance synaptic signalling and foster resilience against depressive and anxiety disorders. Integrating insights from molecular mechanisms to behavioural endpoints is thus critical for translating NO-based interventions into clinical practice.
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Nitric Oxide Modulation in Affective Disorders publication trend
The graph below shows the total number of articles in nitric oxide modulation in affective disorders across all publications each year (not limited to Nature Index journals).
Technical terms
Nitric oxide (NO): A gaseous neurotransmitter that diffuses across cell membranes to regulate neuronal communication and vascular tone.
Nitric oxide synthase (NOS): Enzymes (nNOS, eNOS, iNOS) that catalyse NO production from L-arginine.
S-nitrosylation: A covalent modification of cysteine residues by NO, altering protein function and signalling.
Nitration: Addition of a nitro group to tyrosine residues, often impairing receptor activity or protein–protein interactions.
cGMP: Cyclic guanosine monophosphate, a second messenger generated upon NO-activated guanylyl cyclase stimulation.
Neuroplasticity: The capacity of neural circuits to reorganise connectivity and strength in response to experience or injury.
References
- nNOS-induced tyrosine nitration of TRKB impairs BDNF signaling and restrains neuronal plasticity. Progress in Neurobiology (2023).
- “NO” Time in Fear Response: Possible Implication of Nitric-Oxide-Related Mechanisms in PTSD. Molecules (2023).
- Interaction between HTR2A rs3125 and negative life events in suicide attempts among patients with major depressive disorder: a cross-sectional study. BMC Psychiatry (2024).
- Nitric oxide signalling and antidepressant action revisited. Cell and Tissue Research (2019).
- Nitric Oxide Synthase Inhibitors as Antidepressants. Pharmaceuticals (2010).
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