Bipolar Disorder 1 (BD1) victimizes nearly three million people in the U.S. alone. Moreover, the treatment for BD1, while ineffective for many patients, includes lithium and other drugs with onerous side effects. The suicide rate is very high. Nevertheless, an alternative exists based on low and safe non-invasive electrical stimulation of the skull using a transcranial direct current stimulator (tDCS). No drugs needed.

The medical acceptance of this alternative, however, requires the final testing of my hypothesis that manic and depressive phases in BD1 result from a failure of interhemispheric inhibition in the frontal lobes. I will offer the reasoning for the hypothesis, the initial testing, and the explanation for why it should work.

Lesions to the right frontal lobe often produce manic episodes, and lesions to the left frontal lobe often produce depression. Bipolar patients do not generally have such lesions, but they do have temporary equivalents. They must be temporary, since in BD1 we have alternations between manic and depressive phases, with “neutral” periods called “euthymic.”

In my hypothesis, a failure of interhemispheric inhibition takes place in the frontal lobes of bipolar patients. To be specific, when the electrical activation of the left side overwhelms that of the right, the left frontal lobe dominates, thus leading to exaggerated states of elation (mania). Dominance in activation by the right side, in turn, leads to states of depression. An EEG cap will help determine whether subjects are in manic or depressive states.

We experimentally reduced high elation in reaction to photos from the International Affective Picture Scale by applying an extremely small current, using tDCS, 1.8 mA, on the right hemisphere of 24 healthy subjects. (G. Munevar et al, Limite, Vol. 13, No. 43, 2018, pp. 80-88.) It is crucial that we now test the hypothesis on about 10 Bipolar 1 patients for a few months, to make sure that this approach will indeed keep mania and depression under control. The experiment will also determine cases in which higher currents or additional doses are needed (much higher doses could be provided by TMS). A small headache is about the most significant ill effect a subject may have.

What explains the nature of BP1 as proposed here? In her remarkable stem-cell study of neurons derived from the skin cells of BP1 subjects, Susan O'Shea found extraordinary electrical hyper-activity, likely because neurons coming from bipolar patients had far more calcium-ion channels, a genetic problem. This unusual hyperactivity explains why the frontal lobe inter-hemispheric inhibition mechanism gets stuck in a manic or a depressive phase, instead of returning to near equilibrium. A small initial difference led to a very large current increase. (S. O'Shea et al, Translational Psychiatry, 4 (3), 2014.12).

The money from the award would allow us to pay BP1 patients for participating in this study and our technicians for doing the EEG cap observations and tDCS applications.