Bipolar Mania

The first descriptions of bipolar mania over 100 years ago indicate awareness that changes in purine metabolism are correlated with mania. More recent studies have confirmed that the degree of purine metabolism disruption is correlated with symptom severity and hospital length of stay: purine metabolism returning to normal indicates that the episode has resolved, whereas symptom resolution without purine metabolism normalization is likely to be temporary followed by symptom recurrence.

Decreased need for sleep/ dissolution of circadian rhythm and grandiose delusions are some of the most characteristic symptoms of mania. These symptoms are tightly correlated in clinical practice, purine metabolism provides a common pathway.

 Adenosine is a purine that initiates sleep: decreased adenosine may be to blame for decreased need for sleep. Guanosine is also a purine: guanosine-mimicking medications can cause grandiose delusions in susceptible individuals. Purine metabolism disruptions that cause decreased adenosine are expected to cause a compensatory increase in guanosine.

Many treatments for mania are also useful for epilepsy. Epilepsy is increasingly understood as a disorder of adenosine metabolism: adenosine is the body's primary anti-seizure chemical and chronic adenosine deficiency contributes to the development of epilepsy following injury. 

Purine-metabolism mechanisms unite the variety of bipolar treatments: medicinal (lithium, valproate, benzodiazepines, etc.) and procedural (ECT, etc.). These also explain the curiosity that allopurinol, a purine-mimicking drug, incidentally improves mania prevention.