A reverse-translational study of dysfunctional exploration in psychiatric disorders: from mice to men.

Full Abstract

CONTEXT: Bipolar mania and schizophrenia are recognized as separate disorders but share many commonalities, which raises the question of whether they are the same disorder on different ends of a continuum. The lack of distinct endophenotypes of bipolar mania and schizophrenia has complicated the development of animal models that are specific to these disorders. Exploration is fundamental to survival and is dysregulated in these 2 disorders. Although exploratory behavior in rodents has been widely studied, surprisingly little work has examined this critical function in humans. OBJECTIVES: To quantify the exploratory behavior of individuals with bipolar mania and schizophrenia and to identify distinctive phenotypes of these illnesses. DESIGN: Static group comparison by the use of a novel human open field paradigm, the human Behavioral Pattern Monitor (BPM). SETTING: Psychiatric hospital. PARTICIPANTS: Fifteen patients with bipolar mania and 16 patients with schizophrenia were compared with 26 healthy volunteers in the human BPM. The effects of amphetamine sulfate, the selective dopamine transporter inhibitor GBR12909, and the genetic knockdown of the dopamine transporter were compared with controls in the mouse BPM. MAIN OUTCOME MEASURES: The amount of motor activity, spatial patterns of activity, and exploration of novel stimuli were quantified in both the human and mouse BPMs. RESULTS: Patients with bipolar mania demonstrated a unique exploratory pattern, characterized by high motor activity and increased object exploration. Patients with schizophrenia did not show the expected habituation of motor activity. Selective genetic or pharmacologic inhibition of the dopamine transporter matched the mania phenotype better than the effects of amphetamine, which has been the criterion standard for animal models of mania. CONCLUSIONS: These findings validate the human open field paradigm and identify defining characteristics of bipolar mania that are distinct from those of schizophrenia. This cross-species study of exploration calls into question an accepted animal model of mania and should help to develop more accurate human and animal models, which are essential to the identification of the neurobiological underpinnings of neuropsychiatric disorders.

Author information

Author/s: Perry, William (W); Minassian, Arpi (A); Paulus, Martin P (MP); Young, Jared W (JW); Kincaid, Meegin J (MJ); Ferguson, Eliza J (EJ); Henry, Brook L (BL); Zhuang, Xiaoxi (X); Masten, Virginia L (VL); Sharp, Richard F (RF); Geyer, Mark A (MA);

Affiliation: Department of Psychiatry, University of California, San Diego, 9500 Gilman Dr, MC 0804, La Jolla, CA 92093-0804, USA.

Grants: R01-MH071916 (Agency:NIMH NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.

Journal: Archives of general psychiatry (Arch Gen Psychiatry), published in United States. (Language: eng)

Reference: 2009-Oct; vol 66 (issue 10) : pp 1072-80

Dates: Created 2009/10/06; Completed 2009/10/13;

PMID: 19805697, status: MEDLINE (last retrieval date: 10/13/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.