Review: no reliable biological markers yet for bipolar disorder staging or psychedelic effects

The question

Can biological markers track the worsening of bipolar disorder over time, and do ketamine and psychedelics act on the same biological pathways?

What they did

The authors carried out a narrative (non-systematic) review. They searched PubMed/MEDLINE, Scopus and Web of Science in December 2025 and February 2026, favouring human studies of bipolar disorder, especially those following people over time or grouping them by illness stage, plus meta-analyses, systematic reviews, and early laboratory and early-phase clinical work on mechanisms. They then compared these biomarker findings with what is known about how ketamine and psychedelics act.

What they found

More advanced bipolar disorder was linked to abnormalities in inflammation, nerve-growth signalling, brain structure and function on scans, and epigenetic changes (chemical marks that switch genes on or off). But the results were inconsistent, usually small, and often came from single-time-point studies. Many markers seemed to reflect a person’s current mood state rather than cumulative damage from the illness: blood BDNF and inflammatory markers were not specific, functional brain imaging findings shifted with mood, and epigenetic changes were patchy. Ketamine and psychedelics affected several of the same pathways, mostly in animal models and less so in humans, and most of that human mechanistic evidence came from unipolar treatment-resistant depression rather than bipolar disorder. Early bipolar-specific work, mainly in bipolar II depression, suggested that psilocybin- and 5-MeO-DMT-based approaches may be feasible and may reduce depression symptoms under carefully controlled conditions.

The fine print

This was a narrative review with a structured but non-systematic search, so relevant studies may have been missed and no formal pooling or risk-of-bias assessment was done. The authors report no participant numbers, effect sizes or dose details. Much of the mechanistic evidence comes from animal studies or from unipolar depression, not bipolar disorder, and the bipolar-specific psychedelic studies are described only as preliminary. This summary is based on the abstract alone.

What it means

At present there is no dependable blood test or brain scan marker that can stage bipolar disorder or show whether a treatment is slowing the illness. Ketamine and psychedelics act on plausible biological pathways, but evidence that they change the course of bipolar disorder rather than temporarily easing symptoms is still indirect.

Evidence grade: Very low. A narrative, hypothesis-generating review based on a deliberately non-systematic literature search, with no pooled data or quality scoring of the included studies.

This summary is based on the study’s published abstract.