Individual differences in psychotic effects of ketamine are predicted by brain function measured under placebo.

Full Abstract

The symptoms of major psychotic illness are diverse and vary widely across individuals. Furthermore, the prepsychotic phase is indistinct, providing little indication of the precise pattern of symptoms that may subsequently emerge. Likewise, although in some individuals who have affected family members the occurrence of disease may be predicted, the specific symptom profile may not. An important question, therefore, is whether predictive physiological markers of symptom expression can be identified. We conducted a placebo-controlled, within-subjects study in healthy individuals to investigate whether individual variability in baseline physiology, as assessed using functional magnetic resonance imaging, predicted psychosis elicited by the psychotomimetic drug ketamine and whether physiological change under drug reproduced those reported in patients. Here we show that brain responses to cognitive task demands under placebo predict the expression of psychotic phenomena after drug administration. Frontothalamic responses to a working memory task were associated with the tendency of subjects to experience negative symptoms under ketamine. Bilateral frontal responses to an attention task were also predictive of negative symptoms. Frontotemporal activations during language processing tasks were predictive of thought disorder and auditory illusory experiences. A subpsychotic dose of ketamine administered during a second scanning session resulted in increased basal ganglia and thalamic activation during the working memory task, paralleling previous reports in patients with schizophrenia. These results demonstrate precise and predictive brain markers for individual profiles of vulnerability to drug-induced psychosis.

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Author information

Author/s: Honey, Garry D (GD); Corlett, Philip R (PR); Absalom, Anthony R (AR); Lee, Michael (M); Pomarol-Clotet, Edith (E); Murray, Graham K (GK); McKenna, Peter J (PJ); Bullmore, Edward T (ET); Menon, David K (DK); Fletcher, Paul C (PC);

Affiliation: Department of Psychiatry, Brain Mapping Unit and Behavioural and Clinical Neurosciences Institute, University of Cambridge, School of Clinical Medicine, Cambridge CB2 2QQ, United Kingdom.

Grants: (Agency:United Kingdom Wellcome Trust)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2008-Jun; vol 28 (issue 25) : pp 6295-303

Dates: Created 2008/06/19; Completed 2008/07/10;

PMID: 18562599, status: MEDLINE (last retrieval date: 11/6/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adult
Brain - drug effects; physiology
Female
Humans
Individuality
Ketamine - adverse effects
Learning - drug effects; physiology

Learning - drug effects; physiology
Magnetic Resonance Imaging - methods
Male
Placebos - adverse effects
Predictive Value of Tests
Psychomotor Performance - drug effects; physiology
Psychoses, Substance-Induced - physiopathology; psychology

Associated Chemicals: Placebos (0) ; Ketamine (6740-88-1)

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