Greater vulnerability to the amnestic effects of ketamine in males

Rationale Gender differences both in response to ketamine in animals and general cognitive functioning in humans have been observed and suggested to be related to modulatory effects of sex hormones on N-methyl-D-aspartate receptor (NMDA-R) functioning. Objectives The current study aimed to determine whether there were gender differences in response to ketamine in humans. Methods Behavioral data including positive and negative symptoms (Brief Psychiatric Rating Scale), perceptual alterations (Clinician-Administered Dissociative States Scale, CADSS), and high and anxiety states (Visual Analog Scale) from 295 subjects who participated in a total of 11 placebo-controlled ketamine studies were analyzed. In a subset of subjects, memory (Hopkins Verbal Learning Task: HVLT, n=108) and attention (continuous performance task, n=177) data were also analyzed. Results Male participants showed a greater performance decrement on the HVLT after ketamine administration compared to women. Men also reported a greater subjective sense of memory impairment on a CADSS subscale. No other gender differences in behavioral or cognitive measures were observed. Conclusions Men showed a greater vulnerability to the amnestic effects of ketamine than women. Possible explanations of these findings are neuroanatomical and cognitive differences in processing of words in men and women and interactions between sex hormones and NMDA-R function.