Assuming depression to be an evolutionary hibernation reaction, what helps to stabilize it? Obviously hibernation is marked by low appetite, low sex drive, low energy and lack of enjoyment of activities all of which serve to keep the animal in situ. These are core symptoms of depression, as is poor concentration, more likely related to dopamine excess. If again we assume that auto-receptors are turned off as neurotransmitters arch toward depletion a standoff ensues in which the two remain in relative downturn during the duration of the hibernated shift, about six months, and usually winter dominated as are seasonally triggered depressive phenomena. With auto receptors turned off, at least during the day, dopamine can surge, interfering with concentration, and, in manics, leading to linguistic deterioration.
We attempt to break the stalemate with antidepressants which flood the synapse with neurotransmitters and reignite the auto receptors. This tones down dopamine so that the individual can think again, fertilizing the frontal areas with conceptual activity which stimulates BDNF, VEGF production. The latter have a euphorigenic effect which is seen with ketamine. Manics use sleep deprivation to keep the auto receptors off all through the night which floods the brain with dopamine and can lead to a stimulant like psychosis. Dopamine blocking agents then calm the storm. Efforts to stabilize depolarization are successful, including anticonvulsants, lithium, and ECT, all of which hyper-polarize nerves.
Lithium has an antisuicide effect, mood stabilizing property and antidepressant impact. Research has shown that communities with higher natural levels of lithium in the water supply have a lower suicide rate. Bipolar disorder used to be treated by sending wealthy patients to European mineral baths which were found to have a higher lithium content. Could it be that Pleistocene era Homo sapiens evolved in an environment of higher lithium content in the water? Our central nervous systems are accustomed then to a higher lithium level which makes us all relatively lithium deficient. Some react to this deficiency with depression, mania or psychosis. In essence lithium is a neuroactive protovitamin. Some nervous systems are able to handle the relative lack, others are not. By stabilizing the depolarization dynamic, the auto-receptors are turned on, neurotransmission is protected and dopamine is suppressed by the activity of the auto-receptors.
We need to be aware of the Pleistocene environment we evolved in. Deficiencies may lead to variable levels of vulnerability to psychopathology. Perhaps we should add lithium to the water supply of all people, but some might develop hypothyroidism or kidney problems if the level is too high. Yet, a slight increase in lithium consumption might have a marked effect on suicide prevention.