Pathophysiology

Alcohol-related psychosis most likely relates to dopamine in the limbic and possibly other systems. The dopamine hypothesis often is applied to psychosis involving excessive activity of the dopaminergic system. Animal studies have shown dopaminergic activity to increase with increased release of dopamine when alcohol is administered. On the other hand, alcohol withdrawal generates a decrease in the firing of dopaminergic neurons in the ventral tegmental area and a decrease in release of dopamine from the neuron.
The pathophysiological systems of intoxication, withdrawal, and alcohol idiosyncratic intoxication all are different, and their relationships to psychosis are unclear. To some degree, they all involve the neurotoxicity of alcohol with resultant neurological, genetic, biochemical, and physiological pathology.
Alcohol intoxication results in disinhibition, sedation, and anesthesia. Acute depression of the cerebral cortex and reticular activating system results. The pathophysiology of alcoholism involves alterations in short-term membrane regulation and long-term effects on gene expression.
In patients who are dependent on alcohol, alcohol withdrawal results in adrenergic hypersensitivity of the limbic system and brainstem. Thiamine deficiency also is a contributing factor and is known to be associated with more severe episodes of withdrawal psychosis, which may present as a delirious state known as Wernicke-Korsakoff syndrome (WKS). Psychosis is not considered a symptom in uncomplicated alcohol withdrawal in patients who are not dependent on alcohol. The psychosis often is self-limited and recurs with subsequent withdrawals.

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