The Monoamine-Glutamate Continuum of Depression: A Neurobiological Framework for Precision Psychiatry.
Pharmaceuticals (Basel, Switzerland) April 24, 2026 Pietro Carmellini, Alessandro Cuomo, Maria Beatrice Rescalli et al.
Depression likely arises from a mix of two interacting biological problems: imbalances in monoamine neurotransmitters (like serotonin) and disruptions in glutamate signaling that impair the brain's ability to adapt and form new connections. These two systems can combine in different ways across individuals, helping explain why some people respond to standard antidepressants while others do not. Rapid-acting treatments such as ketamine work by directly targeting the glutamate system to boost synaptic plasticity, offering faster relief, especially for treatment-resistant depression. A framework called the 'monoamine-glutamate continuum' may guide future precision psychiatry by matching treatments to each person's specific neurobiological profile.