Matt and psychiatrist Jon Berner chat about the potential of lithium, a generic drug typically used as a mood stabilizer in illnesses such as bipolar disorder, as an Alzheimer's disease and/or life extension drug. They discuss the data supporting lithium's potential effectiveness in preventing premature dementia, practical considerations and challenges around lithium dose optimization, and possible biological mechanisms that explain lithium's effectiveness. They also delve into the various challenges of studying lithium's effects on humans as well as useful further directions for lithium research.

Jon has been in solo psychiatric practice at Woodinville Psychiatric in Washington since 1997. He spent several years working at the Monroe Correctional Complex, a Washington State Department of Corrections prison. His specialties include brain disorders, particularly bipolar and psychotic illnesses, complex pain, addiction, and "undiagnosed" neuropsychiatric syndromes, and other general psychiatric disorders such as anxiety and depression. Jon has published multiple scientific papers about various topics in the realm of mood disorders and treatments for them. He holds an M.D and a PhD in neuroscience from the University of California, Los Angeles and a B.A. in psychology from Harvard University.

Check out the links below for further information and/or reading about some of the things we discussed in this podcast episode. Note that we do not necessarily endorse or agree with the content of these readings, but present them as supplementary material that may deepen your understanding of the topic after you listen to our podcast. This list is in no way exhaustive, but it’s a good start!

Lithium treatment extends human lifespan: findings from the biomedical database UK Biobank

According to this study, lithium supplementation correlates with an over threefold decrease in mortality among people suffering from affective disorders such as mania and bipolar depression, compared to those who use other anti-psychotic drugs. The study does not go into the likely molecular mechanisms by which lithium might extend human lifespan.

Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial

In a randomized, double-blind trial, 45 patients suffering from mild cognitive impairment received either lithium or a placebo over the span of a year. The trial found a correlation between lithium use and lower cerebrospinal fluid (CSF) concentrations of phosphorylated tau (p-tau), an Alzheimer's disease biomarker. Researchers speculate that lithium may be more beneficial for individuals suffering from mild, as opposed to severe, cognitive impairment.

A triple drug combination targeting components of the nutrient-sensing network maximizes longevity

This study suggests that the combination of trametinib, rapamycin, and lithium increases longevity in flies by nearly 50 percent. Combining the drugs (combinations: lithium + rapamycin, lithium + trametinib, rapamycin + trametinib) extended lifespan by an average of 30 percent, compared to an average lifespan extension effect of 11 percent for each drug in isolation.

Gene-expression differences in peripheral blood between lithium responders and non-responders in the Lithium Treatment-Moderate dose Use Study (LiTMUS)

There exists considerable variability in the clinical response to lithium. This study identified a specific pattern of gene expression in individuals who responded to one month of lithium treatment, with the gene expression changes being related to mechanisms including autophagy regulation, neurite outgrowth, and mitochondrially-mediated apoptosis. The researchers identified differential regulation of 62 genes in people who responded compared to those who didn't respond to lithium treatment.

Lithium treated mood disorders, paroxysmal rhinorrhea and mesial temporal lobe epilepsy

Jon authored this paper presenting evidence for the effectiveness of lithium in mood stabilization via two case studies of mood disorders. In the first, lithium helped control shoplifting and major discrete cycles in a woman suffering from bipolar II disorder. In the second, lithium contributed to mood stabilization in a prison inmate suffering from chronic depression, though the drug also brought about side effects such as diarrhea and sudden attacks of rhinorrhea.

Amyloid-Tau-Neurodegeneration (ATN) Profile

This is the blood biomarker for Alzheimer's disease pathology that Matt and Jon discuss in the podcast episode.