Methods

The tools utilized in this research are the tools available to clinicians worldwide: detailed observation of the patient's symptoms, the medical literature, and broadly available, but poorly systematized chemical structures of psychotherapeutics.

The same chemical structure differences that distinguish different purines also identify differences between clinical uses of medications: stimulants and antipsychotics mimic guanine, CBZ/OXC and BZDs mimic xanthine, while inosine-mimics are typically antidepressants. Certain substructures gain clinical relevance for psychiatric treatment. These psychiatrically relevant substructures can be found in compounds that are not typically considered psychiatric, expanding the pool of therapies and increasing awareness of psychiatrically adverse therapies prescribed for co-morbid conditions.

Purines were the first molecule associated with psychiatric symptoms, identified by the pioneering modern psychiatrist Emil Kraepelin over one hundred years ago. 

Since that time, research has affirmed purine metabolism changes in a variety of disease states. However, prior approaches have typically focused on only one or two purines: uric acid, and/ or ATP. 

This approach expands the variety of purines considered. The initial insight that drove this theory was recognition that in bipolar mania, diminished sleep may be attributable to a specific purine deficit, while typically co-occurring grandiose delusions could be caused by a (compensatory?) purine excess. We had previously known that purine metabolism was changed in bipolar mania: we proposed that purine metabolism may be BOTH the pathophysiology causing the variety of symptoms and ameliorated by treatments PMID 37820933.

There are several aspects of psychiatric research that are as yet unconnected to this purine-based understanding of psychiatric disease, including neuroanatomy, computational circuits and connectivity studies.

By its nature, this work is reductive, similar to the reductive approach used in describing monoamine balance (dopamine, serotonin, epinephrine, and norepinephrine) as the root of psychiatric illness, independent of neuroanatomy. 

Rather than thinking of psychiatric illness as contained completely within the brain, the purine approach considers the whole human system, consistent with emerging evidence of the pivotal role of systemic metabolism and mitochondrial health and consistent with observations of "brain diseases" with demonstrable changes in the remainder of the body (e.g. Parkinson's disease).

This work is restricted to clinical pattern recognition in order to solve clinical problems: any and all patterns identified will be inherently clinically relevant and ready to be put into immediate use by clinicians throughout the world.

This research focuses on the judicious use of pharmaceuticals that have formed the backbone of psychiatric intervention for decades. Purine-based understanding allows for incorporation of prior knowledge and practices into current use, rather than focusing on new interventions to the exclusion of the old.

By expanding the variety of purines considered, and by considering psychoactive compounds as purine-mimics, patterns emerge, explaining both differences in intoxication symptoms of drugs of abuse and also specific differences in apparent mechanism of action of treatments.

Specific testing for the full variety of purines is not clinically available: identification of particular purine imbalances depends on correlating a variety of psychiatric and physical symptoms with hypothesized purine imbalances and apparent specific pharmaceutical action in order to provide more predictive guidance for treatment selection.

This method prioritizes evaluation and treatment of presenting symptoms over establishment of a longitudinal diagnosis or indefinite treatment regimen, traditional treatment goals, but neither of which should supersede the ultimate priority of symptom treatment. 

As symptoms shift, seasonally or related to a variety of other contributing factors, treatment can and should shift to meet the current need. Outcomes suggest that medication regimens can be dramatically simplified and patients remarkably improve. For example, I recently attended a case in which the patient resumed part-time employment and independent living following an 18 month hospitalization for disabling psychosis.