Volume Transmission in the Pathophysiology of Delirium

Delirium is a neurobehavioral syndrome marked by disturbances in cognition, attention, memory, perception and sleep-wake cycle which is common in hospitalized elderly. Although it is one of the oldest conditions known to medicine, its pathophysiology remains poorly understood. Since currently there are no preventive therapies for delirium, elucidation of cellular and molecular underpinnings of this condition may lead to the development of early interventions and thus prevent permanent neurologic damage. Phylogenetically, many neurotransmitters relevant to modern neurology and psychiatry have been present in primitive organisms prior to the existence of a nervous system. Ontogenetically, several neurotransmitters, including acetylcholine, are present before synaptogenesis or neurogenesis, suggesting an alternative communication platform than synaptic transmission. In this article we make the case for the role of volume transmission in the CNS physiology and pathology. This is a signaling modality which engenders a slower but widespread type of information processing, different than the quick point-to-point synaptic-based one. Volume transmission may be responsible for mass-sustained signaling which engenders the states of awareness, cognition or wakefulness, known to “wax and wane” in delirium. Understanding, therefore volume transmission and the information processing fathomed by it may lead us to a better grasp on the pathophysiology of this condition.