Is impulsivity in part a lithium deficiency state?

Psychiatriki. 2018 Jul-Sep;29(3):264-270. doi: 10.22365/jpsych.2018.293.264.

Abstract

Lithium mechanisms of action are related to the function of many enzymes, hormones, vitamins, and growth factors. In humans, lithium treatment has been associated with humoral and structural evidence of neuroprotection, such as increased expression of antiapoptotic genes, inhibition of cellular oxidative stress, synthesis of brain-derived neurotrophic factor, cortical thickening, increased grey matter density, and hippocampal enlargement. Lithium, in pharmacological doses, has been used successfully in treating bipolar disorders, and has been shown to decrease suicidality and violent crime in this situation. The guidelines of major psychiatric association name lithium as a first-line therapy for bipolar disorder. From the other hand, impulsivity is a core feature of bipolar disorder. Increased levels of this dimensional trait are present not only during acute phases of the illness but also during euthymia. Increased impulsivity worsens clinical prognosis of bipolar disorder due to its association with several severity indices, such as substance abuse or dependence, suicidal behavior, and poorer functional outcome. A wide range of intracellular responses may be secondary to the inhibition of glycogen synthase kinase-3 beta (GSK3β) by lithium, while genetic variability at GSK3β gene was found to be associated with increased impulsivity in bipolar patients. Although impulsivity has been traditionally linked to dysregulation of serotonergic and dopaminergic systems, some authors have proposed that lithium could reduce impulsivity levels by means of its capacity to regulate the aforementioned neurotransmitter systems. Moreover, lithium in trace amounts, as occurs in drinking water, has been inversely related to suicidal mortality, aggression and homicidal violence. These findings pose the question of whether the prospect of adding lithium to drinking water is realistic, weighing the benefits and potential risks. It seems also that in the competition for survival, those entities that best minimized lithium toxicity and maximized the benefits of lithium action had an edge in the competition to survive and reproduce. Finally, lithium has been reported to increase the volume of the prefrontal cortex and anterior cingulate gyrus. Evidence from both basic and clinical researches support that lithium may decrease impulsivity and may at least partially, exert its antisuicidal effect via reinforcing "top-down brakes" of impulsive action. Considering the research data, we may suggest that even natural lithium level intake can influence impulsivity, a possible core factor that mediate to the manifestation of both suicidality and aggressiveness, or even criminality. Moreover, we may suggest that a lithium deficiency state may precipitate these situations.

Publication types

  • Review

MeSH terms

  • Antimanic Agents / adverse effects
  • Antimanic Agents / therapeutic use*
  • Bipolar Disorder / etiology
  • Bipolar Disorder / psychology*
  • Humans
  • Impulsive Behavior*
  • Lithium / deficiency*
  • Lithium / therapeutic use
  • Lithium Compounds
  • Suicidal Ideation
  • Violence

Substances

  • Antimanic Agents
  • Lithium Compounds
  • Lithium