Bipolar Mania and Epilepsy Pathophysiology and Treatment May Converge in Purine Metabolism: A New Perspective on Available Evidence

Overview

Journal Neuropharmacology

Specialties Neurology
Pharmacology

Date 2023 Oct 11

PMID 37820933

Authors

Scott D Daniels

Detlev Boison

Affiliations

Soon will be listed here.

Abstract

Decreased ATPergic signaling is an increasingly recognized pathophysiology in bipolar mania disease models. In parallel, adenosine deficit is increasingly recognized in epilepsy pathophysiology. Under-recognized ATP and/or adenosine-increasing mechanisms of several antimanic and antiseizure therapies including lithium, valproate, carbamazepine, and ECT suggest a fundamental pathogenic role of adenosine deficit in bipolar mania to match the established role of adenosine deficit in epilepsy. The depletion of adenosine-derivatives within the purine cycle is expected to result in a compensatory increase in oxopurines (uric acid precursors) and secondarily increased uric acid, observed in both bipolar mania and epilepsy. Cortisol-based inhibition of purine conversion to adenosine-derivatives may be reflected in observed uric acid increases and the well-established contribution of cortisol to both bipolar mania and epilepsy pathology. Cortisol-inhibited conversion from IMP to AMP as precursor of both ATP and adenosine may represent a mechanism for treatment resistance common in both bipolar mania and epilepsy. Anti-cortisol therapies may therefore augment other treatments both in bipolar mania and epilepsy. Evidence linking (i) adenosine deficit with a decreased need for sleep, (ii) IMP/cGMP excess with compulsive hypersexuality, and (iii) guanosine excess with grandiose delusions may converge to suggest a novel theory of bipolar mania as a condition characterized by disrupted purine metabolism. The potential for disease-modification and prevention related to adenosine-mediated epigenetic changes in epilepsy may be mirrored in mania. Evaluating the purinergic effects of existing agents and validating purine dysregulation may improve diagnosis and treatment in bipolar mania and epilepsy and provide specific targets for drug development.

References

ODonovan S, Sullivan C, Koene R, Devine E, Hasselfeld K, Moody C . Cell-subtype-specific changes in adenosine pathways in schizophrenia. Neuropsychopharmacology. 2018; 43(8):1667-1674. PMC: 6006250. DOI: 10.1038/s41386-018-0028-6. View

Ribeiro J, Sebastiao A . Caffeine and adenosine. J Alzheimers Dis. 2010; 20 Suppl 1:S3-15. DOI: 10.3233/JAD-2010-1379. View

Choi H, Niu J, Neogi T, Chen C, Chaisson C, Hunter D . Nocturnal risk of gout attacks. Arthritis Rheumatol. 2014; 67(2):555-62. PMC: 4360969. DOI: 10.1002/art.38917. View

Gilbert D, Pyzik P, Freeman J . The ketogenic diet: seizure control correlates better with serum beta-hydroxybutyrate than with urine ketones. J Child Neurol. 2001; 15(12):787-90. DOI: 10.1177/088307380001501203. View

Beghi E . The Epidemiology of Epilepsy. Neuroepidemiology. 2019; 54(2):185-191. DOI: 10.1159/000503831. View

Elmenhorst D, Basheer R, McCarley R, Bauer A . Sleep deprivation increases A(1) adenosine receptor density in the rat brain. Brain Res. 2009; 1258:53-8. PMC: 3623949. DOI: 10.1016/j.brainres.2008.12.056. View

Bauer M, Pfennig A . Epidemiology of bipolar disorders. Epilepsia. 2005; 46 Suppl 4:8-13. DOI: 10.1111/j.1528-1167.2005.463003.x. View

Von Lubitz D, Carter M, Deutsch S, Lin R, Mastropaolo J, Meshulam Y . The effects of adenosine A3 receptor stimulation on seizures in mice. Eur J Pharmacol. 1995; 275(1):23-9. PMC: 10788692. DOI: 10.1016/0014-2999(94)00734-o. View

Saccarello A, Montarsolo P, Massardo I, Picciotto R, Pedemonte A, Castagnaro R . Oral Administration of S-Adenosylmethionine (SAMe) and Lactobacillus Plantarum HEAL9 Improves the Mild-To-Moderate Symptoms of Depression: A Randomized, Double-Blind, Placebo-Controlled Study. Prim Care Companion CNS Disord. 2020; 22(4). DOI: 10.4088/PCC.19m02578. View

10.

Cheffer A, Castillo A, Correa-Velloso J, Goncalves M, Naaldijk Y, Nascimento I . Purinergic system in psychiatric diseases. Mol Psychiatry. 2017; 23(1):94-106. DOI: 10.1038/mp.2017.188. View

11.

Reiter S, Simmonds H, Webster D, Watson A . On the metabolism of allopurinol. Formation of allopurinol-1-riboside in purine nucleoside phosphorylase deficiency. Biochem Pharmacol. 1983; 32(14):2167-74. DOI: 10.1016/0006-2952(83)90222-8. View

12.

Wright J . Mania following sleep deprivation. Br J Psychiatry. 1993; 163:679-80. DOI: 10.1192/bjp.163.5.679. View

13.

Machado-Vieira R, Lara D, Souza D, Kapczinski F . Purinergic dysfunction in mania: an integrative model. Med Hypotheses. 2002; 58(4):297-304. DOI: 10.1054/mehy.2001.1543. View

14.

Scanziani M, Capogna M, Gahwiler B, Thompson S . Presynaptic inhibition of miniature excitatory synaptic currents by baclofen and adenosine in the hippocampus. Neuron. 1992; 9(5):919-27. DOI: 10.1016/0896-6273(92)90244-8. View

15.

Detich N, Hamm S, Just G, Knox J, Szyf M . The methyl donor S-Adenosylmethionine inhibits active demethylation of DNA: a candidate novel mechanism for the pharmacological effects of S-Adenosylmethionine. J Biol Chem. 2003; 278(23):20812-20. DOI: 10.1074/jbc.M211813200. View

16.

Perugi G, Medda P, Toni C, Mariani M, Socci C, Mauri M . The Role of Electroconvulsive Therapy (ECT) in Bipolar Disorder: Effectiveness in 522 Patients with Bipolar Depression, Mixed-state, Mania and Catatonic Features. Curr Neuropharmacol. 2017; 15(3):359-371. PMC: 5405614. DOI: 10.2174/1570159X14666161017233642. View

17.

Gooderham M, Papp K . Selective Phosphodiesterase Inhibitors for Psoriasis: Focus on Apremilast. BioDrugs. 2015; 29(5):327-39. PMC: 4626529. DOI: 10.1007/s40259-015-0144-3. View

18.

Schioldann J . 'On periodical depressions and their pathogenesis' by Carl Lange (1886). Hist Psychiatry. 2011; 22(85 Pt 1):108-30. DOI: 10.1177/0957154X10396807. View

19.

Jin B, Aung T, Geng Y, Wang S . Epilepsy and Its Interaction With Sleep and Circadian Rhythm. Front Neurol. 2020; 11:327. PMC: 7225332. DOI: 10.3389/fneur.2020.00327. View

20.

Barbini B, Bertelli S, Colombo C, Smeraldi E . Sleep loss, a possible factor in augmenting manic episode. Psychiatry Res. 1996; 65(2):121-5. DOI: 10.1016/s0165-1781(96)02909-5. View