This one question has puzzled and continues to puzzle the scientific community. It is known that in the brains of people with bipolar, schizophrenia, and other mood disorders, the volume of gray matter is decreased relative to healthy controls. Lithium works very well for a large portion these people ergo the hypothesis that lithium works by increasing gray matter in the brain.
G.J. Moore, J.M. Bebchuk, K. Hasanat, G. Chen, N. Seraji-Bozorgzad, I.B. Wilds et al. Lithium increases N-acetyl-aspartate in the human brain: In vivo evidence in support of bcl-2’s neurotrophic effects? Biol Psychiatry, 48:1-8, 2000.Indeed this seemed to be true from imaging studies that appeared to show an increase of gray matter in people who take lithium (for both people with and without bipolar). However a recent study
Cousins et al. Lithium, Gray Matter, and Magnetic Resonance Imaging Signal. Biological Psychiatry. 73(7):652-657, 2013,shows that the when the lithium ions are mixed with water, they show increased volume on the images. This finding contradicts the hypothesis that lithium works by increasing the volume of the brain.
We are still left with the puzzle of why and how lithium works. Without a definitive scientific explanation, we are left to rely on phenomenology to determine whether lithium works for a given person. It is up to the patient based on their first-person experience to determine whether lithium works for them. This is why a respectful therapeutic relationship is needed, and the role of the patient's experience of the world must largely influence treatment. Despite the wishful thinking of some doctors or psych hospital staff, doctors cannot determine on their own whether a particular course of treatment is going to work.
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