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Purinergic system and suicidal behavior: exploring the link between adenosine A2A receptors and depressive/impulsive features

Molecular Psychiatry volume 25, pages 512–513 (2020)Cite this article

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In recent years, there has been growing interest in the role of purinergic system as a potential target for novel pharmacological agents for treating psychiatric diseases [1, 2]. Purinergic mechanisms on specific receptor subtypes have been linked to the regulation of mood and behavior [1]. The authoritative review by Cheffer et al. [3] recently provided an update on pathophysiological processes of purinergic signaling involved in the development of mental disorders, including depression, bipolar disorder, schizophrenia, autism, anxiety, and attention deficit/hyperactivity disorder. Abnormal neurotransmission and neuromodulation mediated by the purine nucleoside adenosine, through relevant interactions with purinergic P1 (A1, A2A, A2B, and A3) receptors, may at least partially explain the occurrence of these mental disorders. However, the neurobiological and neurochemical models summarized in this review might benefit from an additional perspective on the possible involvement of purinergic system in the transdiagnostic suicide-related domain, potentially involving the adenosine A2A receptors.

In addition, a second pathway linking purinergic system to suicide risk might involve impulsivity, a key element of the stress–diathesis model of suicidal behavior and one of the most important intermediate phenotypes of suicide [13, 14]. Ortiz et al. [2], reviewing purinergic system role in mood disorders, highlighted that dysfunctions of purinergic signaling—either at a genetic, biochemical, or functional level—may lead to altered behaviors, including impulsivity, aggression, and changes in mood. Indirect evidence on the involvement of purinergic system in impulsivity is provided by studies estimating higher levels of adenosine metabolites in both humans and mice [15]. In addition, mental disorders characterized by increased impulsivity, such as bipolar disorder and mania, have been found to be associated with an increase of serum uric acid [16]. Once more, it might be postulated an involvement of adenosine A2A receptors, since deficits in their function may promote impulsive responses [17]. Thus, impulsivity, contrary to depression, might be associated with an inhibition of adenosine A2A receptor signaling.

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Authors and Affiliations

  1. Department of Medicine and Surgery, University of Milano Bicocca, Milano, Italy

    Francesco Bartoli, Massimo Clerici & Giuseppe Carrà

  2. Division of Psychiatry, University College London, London, W1T 7NF, UK

    Giuseppe Carrà

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Correspondence to Francesco Bartoli.

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Bartoli, F., Clerici, M. & Carrà, G. Purinergic system and suicidal behavior: exploring the link between adenosine A2A receptors and depressive/impulsive features. Mol Psychiatry 25, 512–513 (2020). https://doi.org/10.1038/s41380-018-0057-x

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