Soft Cells: Neurons, Lithium, and Hope for Bipolar Disorder Treatment

“When I was diagnosed with bipolar disorder, the first medication I tried was lithium,” my friend John tells me. Now 36, he was initially diagnosed with bipolar disorder at 19. “Lithium changed me. Before I had struggled with the most basic tasks of living and was consumed by either extraordinary despair or bursts of boundless enthusiasm that ultimately resulted in emotional crashing. Lithium made me stable. It worked so well that I didn’t mind the countless blood tests, the weight gain, or the breakouts. Things were awesome.” And things continued to be awesome for over a year. “Then one day it stopped. This mysterious salt that had returned me to the land of the productive, stable, and emotionally safe stopped working. It was as if someone had accidentally pressed the off button. The realization that I would have to start all over in the search of psychological well-being was devastating. It was also deeply confusing—why did this happen? At the time, no one knew.”

Almost 20 years later, researchers are finally on the road to answering the question of why lithium can stop working. Not only that, but they also shed light on both the cellular qualities of bipolar disorder and lithium’s mechanism of action, both of which are amongst the longest-enduring mysteries in mental health. A team of researchers led by Dr. Rusty Gage, a professor at Salk’s Laboratory of Genetics, reprogrammed the skin cells of six donors with bipolar disorder as stem cells and induced neuron development. These neurons along with neurons from healthy donors were then stimulated to evaluate responsiveness and compared to determine differences in sensitivity. The findings confirmed what many had long suspected: the cells from people with bipolar disorder are more sensitive to stimuli. The study—the first of its kind—provided concrete evidence that bipolar disorder operates on a cellular level, and allowed the scientists to begin the process of hypothesizing what roles this cellular sensitivity plays in the switch between mood states. Dr. Gage says, “After a few months, it’s possible that this hyperexcitability becomes too much for the cell to handle and it crashes into a less excitable state. That could signal the shift between the depression and mania that patients experience.”

The initial findings of the study also allowed for further exploration into the interaction between neural cells and medication. Since lithium had been an effective treatment for half of the donors with bipolar disorder, the researchers conducted experiments to observe cellular response when submerged in a lithium bath to see if there was a difference in activation. Here, the results were unexpected; the responsiveness to lithium was sharply divided between the two groups. “Cells from lithium responder patients showed weakened excitability after growing in the lithium. But cells from patients who hadn’t been helped by the drug remained hyperexcitable.” The results appear to confirm that lithium works by inducing important neural changes that reduce sensitivity. While these findings do not yet provide a clear picture of why some cells respond this way and others don’t, understanding the method of action is the first step to further investigation into both the details of lithium response and the development of new drugs that address neural hyperexcitability.

While expanded pharmaceutical therapies are indeed promising to the millions of people living with bipolar disorder, the most effective bipolar disorder treatment combines psychotropic interventions with targeted psychotherapy. Research has repeatedly confirmed the superiority of combination therapy in alleviating mood symptoms, preventing recurrence, and addressing psychosocial and interpersonal impairment when compared to medication alone. Psychotherapy also improves patient adherence rates, allowing for greater and more consistent benefit from pharmacological therapies. But psychotherapy also does something unique that medication inherently cannot: it empowers you. By guiding you toward deeper levels of self-understanding and giving you concrete emotional and behavioral skills you can use to enhance your quality of life, you gain a more meaningful sense of resilience, autonomy, and self-determination. This emotional and behavioral fortification is not only profoundly transformative when experiencing the benefits of psychotropic medications, it can also augment your ability to handle fluctuations in medication efficacy. If a drug stops working, you still have a deep well of inner resources on which to draw as you seek out more effective pharmacological therapies.

At Bridges to Recovery, we combine thoughtfully designed medication protocols with intensive individual and group psychotherapy modalities targeted to the symptoms of each individual. We believe that addressing the full scope of your emotional and behavioral needs is vital to creating real, sustainable healing that honors your unique psychological and experiential situation. Together, we can work toward improved stability, function, and a renewed sense of self to help you realize your potential.

Bridges to Recovery offers comprehensive treatment for people living with bipolar disorder. Contact us for more information about how our innovative program can help you or your loved one heal from emotional and behavioral distress.