Greater vulnerability to the amnestic effects of ketamine in males.
BACKGROUND
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.


OBJECTIVE
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.
Morgan
Celia J A
CJ
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Perry
Edward B
EB
Cho
Hyung-Sang
HS
Krystal
John H
JH
D'Souza
Deepak Cyril
DC
D000328:Adult; D000647:Amnesia / Q000139:chemically induced* / Q000523:psychology; D001519:Behavior / Q000187:drug effects; D010054:Brief Psychiatric Rating Scale; D003071:Cognition / Q000187:drug effects; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects* / Q000097:blood; D005260:Female; D006801:Humans; D007649:Ketamine / Q000009:adverse effects* / Q000097:blood; D008297:Male; D008568:Memory / Q000187:drug effects*; D011939:Mental Recall / Q000187:drug effects; D010465:Perception / Q000187:drug effects; D012016:Reference Values; D012727:Sex Characteristics; D017678:Sex Distribution; D012737:Sex Factors; D014706:Verbal Learning / Q000187:drug effects
D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine