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Greater vulnerability to the amnestic effects of ketamine in males

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Abstract

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.

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Acknowledgements

The authors wish to acknowledge the critical contributions to this research program made by the research staff of the Biological Studies Unit, West Haven VA Medical Center, including Elizabeth O’Donell, R.N.; Angelina Genovese, R.N.; Sonah Yoo, RPh; and Robert Sturwold, RPh. The authors acknowledge support from the (1) Department of Veterans Affairs (Schizophrenia Biological Research Center, Alcohol Research Center, National Center for PTSD, and Merit Review Program (to JK), (2) National Institute of Alcohol Abuse and Alcoholism (KO2 AA 00261-04 to JK), (3) National Institute of Mental Health (RO1 MH61019-02 to DCD) (P50 MH44866-15 to JK), (4) National Institute of Drug Abuse (1 DA12382-01 to DCD), (5) Stanley Foundation (to DCD) (6) Bogue Fellowship from University College London (to CJAM), and (7) National Alliance for Research in Schizophrenia and Depression (NARSAD) Young Investigator Award (to HSC and EBP).

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Authors and Affiliations

  1. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA

    Celia J. A. Morgan, Edward B. Perry, Hyung-Sang Cho, John H. Krystal & Deepak Cyril D’Souza

  2. Schizophrenia Biological Research Center, Psychiatry Service, 116A, VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT, 06516, USA

    Edward B. Perry, John H. Krystal & Deepak Cyril D’Souza

  3. Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT, USA

    John H. Krystal & Deepak Cyril D’Souza

  4. Clinical Psychopharmacology Unit, University College London, London, UK

    Celia J. A. Morgan

  5. Department of Psychiatry, Yonsei University College of Medicine, Seoul, South Korea

    Hyung-Sang Cho

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  1. Celia J. A. Morgan
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  2. Edward B. Perry
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  5. Deepak Cyril D’Souza
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Correspondence to Deepak Cyril D’Souza.

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Morgan, C.J.A., Perry, E.B., Cho, HS. et al. Greater vulnerability to the amnestic effects of ketamine in males. Psychopharmacology 187, 405–414 (2006). https://doi.org/10.1007/s00213-006-0409-0

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  • DOI: https://doi.org/10.1007/s00213-006-0409-0

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