RESUMEN
A recent NIH epidemiology study found the lifetime prevalence of alcohol use disorder in the United States to be 29%. Alcohol drinking behavior is strongly "learned" via pleasure center activation/reinforcement. Alcohol craving is a powerful desire to drink alcoholic beverages. Craving was added as one of the defining criteria for alcohol use disorder in DSM5, and craving reduction is becoming an increasingly important treatment goal. In the current study, patients with alcohol use disorder received 10 days of inpatient multi-modal treatments at Schick Shadel Hospital (SSH) of Seattle. The treatments included five chemical aversion conditioning sessions that associated alcohol cues (and alcohol) with nausea and emesis. All patients met DSM4 criteria for alcohol use disorder, were heavy drinkers, and reported craving alcohol pre-treatment. Craving reduction was one of the primary treatment goals. This is the first fMRI study to measure the effects of chemical aversion therapy on alcohol craving-related brain activity. Patients were recruited as subjects for the University of Washington (UW) brain scan study following SSH admission but before treatment onset. Prior to treatment, patients reported craving/desire for alcohol. After treatment (after four SSH chemical aversion treatments, again after five SSH chemical treatments, 30 and 90-days post-discharge), these same patients reported avoidance/aversion to alcohol. Most of the participants (69%) reported being still sober 12 months post-treatment. Consistent with a craving reduction mechanism of how chemical aversion therapy facilitates sobriety, results of the UW fMRI brain scans showed significant pre- to post-treatment reductions in craving-related brain activity in the occipital cortex. Additional fMRI brain scan studies are needed to further explore the neurobiological mechanism of chemical aversion therapy treatment for alcohol use disorder, and other substance use disorders for which chemical aversion therapy is used (e.g., opioid dependence and cocaine dependence). Substance use disorders are estimated to affect well over one billion people worldwide.
RESUMEN
BACKGROUND: The pathogenesis of bipolar illness is unknown. A search for common mechanism of action in effective medications has been utilized as a method to gain clues into mechanisms of illness. The recent increase of reports of documented efficacy of first- and second-generation antipsychotics in the control of mania offers a new opportunity to gain insight into the pathophysiological mechanism of bipolar disorder. METHODS: A selected critical review of the literature is performed to gain insights into the effect of antipsychotic medications on ion regulation. RESULTS: Dopamine D(1) and D(2) receptor stimulation increases intracellular sodium concentrations. D(1) and D(2) blockade normalizes stimulated intracellular sodium concentrations, and increases active sodium pump expression. CONCLUSIONS: A similar exercise has previously suggested that lithium and effective anticonvulsants reduce sodium influx in an activity-dependent manner. The current review suggests that antipsychotic medications may have a similar effect by a different mechanism. The role of ion dysregulation in the genesis of mania in bipolar illness needs to continue to be examined.
