From Childhood Woes to Adult Blues: Unmasking the Role of Early Traumas, P2X7 Receptor, and Neuroinflammation in Anxiety and Depression
Abstract
1. Introduction
2. Early-Life Trauma and Neuroinflammation: Setting the Stage
2.1. The Potential Role of Neuroinflammation in the Lasting Effects of Early-Life Traumas
2.2. The Role of Early-Life Stress in Shaping Neuroimmune Responses
3. P2X7 Receptor: A Central Hub in Neuroinflammation
3.1. Role of P2X7R in ATP Signalling
3.2. The Role of P2X7R in Neuroinflammatory Processes
3.3. P2X7 Receptor Distribution and Function in the CNS
3.4. P2X7R’s Involvement in Other Neurological and Psychiatric Conditions
4. P2X7R Activation: A Bridge Between Early Trauma and Anxio-Depressive Behaviours
4.1. Early-Life Stress Leads to Prolonged Enhanced Immune Activation
4.2. Neuroinflammation and Disruption of Brain Development
4.3. Early-Life Immune Activation Leads to Long-Term Neuropsychiatric Disorders
4.4. The Potential Role of the P2RX7 Gene in the Pathogenesis of Depression and Anxiety
Variant ID (SNP) | Associated Condition | Effect of Function | Notes | References |
---|---|---|---|---|
rs2230912 | MDD BD Anxiety | Gain-of-function | One of the most studied SNPs; associated with increased inflammatory response, increased pore activity of P2X7, increased receptor function | [113,124,130,131,132] |
rs1718119 | MDD BD (rapid cycling) | Gain-of-function | Associated with increased cytokine release, increased pore activity of P2X7, increased receptor function | [116,131] |
rs1653625 | MDD BD | Unknown | Possible influence on gene expression through miRNA-mediated regulation | [116,132] |
rs3751143 | MDD BD | Loss-of-function | Diminished receptor activity and associated with altered immune function | [116,133] |
rs7958311 | MDD | Gain-of-function and Loss-of-function | Enhances the P2X7 receptor’s channel activity, impairs the receptor’s ability to form large pores (a critical function for processes such as cytokine release and cell death) | [134] |
rs208294 | MD BD | Gain-of- function | Increases both channel and pore functions of the P2X7 receptor | [125,126] |
rs67881993 | Anxiety | Unknown | Modulating anxiety symptoms through gene–environment interactions conveying a protective effect against increased anxiety in individuals exposed to ELA | [122] |
rs74892325 | MDD | Unknown | Modulating the impact of environmental stressors on mood regulation; the presence of the minor allele was associated with a protective effect against increased depression severity in individuals exposed to ELA | [121] |
rs11615992 | Suicide risk | Regulatory role variant | Potential role in modulating the effects of early-childhood maltreatment on suicidal ideation (protective effect) | [123] |
rs78473339 | Suicide risk | Unknown | Potential role in modulating the effects of early-childhood maltreatment on hopelessness (protective effect) | [123] |
5. P2X7R Modulation and Its Therapeutic Potential in Anxiety and Depression
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Kristof, Z.; Szabo, D.; Sperlagh, B.; Torok, D.; Gonda, X. From Childhood Woes to Adult Blues: Unmasking the Role of Early Traumas, P2X7 Receptor, and Neuroinflammation in Anxiety and Depression. Int. J. Mol. Sci. 2025, 26, 4687. https://doi.org/10.3390/ijms26104687
Kristof Z, Szabo D, Sperlagh B, Torok D, Gonda X. From Childhood Woes to Adult Blues: Unmasking the Role of Early Traumas, P2X7 Receptor, and Neuroinflammation in Anxiety and Depression. International Journal of Molecular Sciences. 2025; 26(10):4687. https://doi.org/10.3390/ijms26104687
Chicago/Turabian StyleKristof, Zsuliet, Dorottya Szabo, Beata Sperlagh, Dora Torok, and Xenia Gonda. 2025. "From Childhood Woes to Adult Blues: Unmasking the Role of Early Traumas, P2X7 Receptor, and Neuroinflammation in Anxiety and Depression" International Journal of Molecular Sciences 26, no. 10: 4687. https://doi.org/10.3390/ijms26104687
APA StyleKristof, Z., Szabo, D., Sperlagh, B., Torok, D., & Gonda, X. (2025). From Childhood Woes to Adult Blues: Unmasking the Role of Early Traumas, P2X7 Receptor, and Neuroinflammation in Anxiety and Depression. International Journal of Molecular Sciences, 26(10), 4687. https://doi.org/10.3390/ijms26104687