Interaction of Sex and Age on the Dissociative Effects of Ketamine Action in Young Healthy Participants

Introduction

Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that produces rapid antidepressant effects at subanaesthetic doses and, acutely, schizophrenia-like and dissociative symptoms. Previous work has shown that the degree of ketamine-induced depersonalisation can predict antidepressant response in depressed patients, but relatively little research has examined whether sex or age moderate ketamine's acute psychotomimetic or dissociative effects in humans. Animal studies and a small number of human reports suggest sex- and age-dependent differences in behavioural, neurochemical and pharmacokinetic responses to ketamine and related glutamatergic processes, and developmental changes in prefrontal cortex maturation occur across late adolescence and early adulthood. Walter and colleagues designed the present study to test whether dissociative symptoms after a single subanaesthetic ketamine infusion differ by sex and whether age within early adulthood (18–30 years) modulates these effects. The investigators assessed dissociative phenomena using the Clinician-Administered Dissociative States Scale (CADSS), which measures derealisation, depersonalisation and amnestic symptoms, in healthy young men and women following ketamine or placebo infusion. Participants were age-matched and the age range was restricted to capture ongoing brain maturation during early adulthood.