Journal article
Using human brain imaging studies as a guide towards animal models of schizophrenia
Neuroscience, Vol.321, pp.77-98
05/30/2015
DOI: 10.1016/j.neuroscience.2015.05.055
PMCID: PMC4664583
PMID: 26037801
Abstract
Schizophrenia is a heterogeneous and poorly understood mental disorder that is presently defined solely by its behavioral symptoms. Advances in genetic, epidemiological and brain imaging techniques in the past half century, however, have significantly advanced our understanding of the underlying biology of the disorder. In spite of these advances clinical research remains limited in its power to establish the causal relationships that link etiology with pathophysiology and symptoms. In this context, animal models provide an important tool for causally testing hypotheses about biological processes postulated to be disrupted in the disorder. While animal models can exploit a variety of entry points towards the study of schizophrenia, here we describe an approach that seeks to closely approximate functional alterations observed with brain imaging techniques in patients. By modeling these intermediate pathophysiological alterations in animals, this approach offers an opportunity to (1) tightly link a single functional brain abnormality with its behavioral consequences, and (2) to determine whether a single pathophysiology can causally produce alterations in other brain areas that have been described in patients. In this review we first summarize a selection of well-replicated biological abnormalities described in the schizophrenia literature. We then provide examples of animal models that were studied in the context of patient imaging findings describing enhanced striatal dopamine D2 receptor function, alterations in thalamo-prefrontal circuit function, and metabolic hyperfunction of the hippocampus. Lastly, we discuss the implications of findings from these animal models for our present understanding of schizophrenia, and consider key unanswered questions for future research in animal models and human patients.
Details
- Title: Subtitle
- Using human brain imaging studies as a guide towards animal models of schizophrenia
- Creators
- Scott S. Bolkan - Columbia UniversityFernanda D. DE CARVALHOChristoph Kellendonk - Columbia University
- Resource Type
- Journal article
- Publication Details
- Neuroscience, Vol.321, pp.77-98
- DOI
- 10.1016/j.neuroscience.2015.05.055
- PMID
- 26037801
- PMCID
- PMC4664583
- NLM abbreviation
- Neuroscience
- ISSN
- 0306-4522
- eISSN
- 1873-7544
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD; OXFORD
- Grant note
- National Institute of Health (NIH): P50MH086404, RO1MH093672 NIH NRSA Fellowship: 1F31MH102041
This research was supported by grants from the National Institute of Health (NIH) (P50MH086404 and RO1MH093672). SSB is supported by an NIH NRSA Fellowship (1F31MH102041).
- Language
- English
- Date published
- 05/30/2015
- Academic Unit
- Psychological and Brain Sciences
- Record Identifier
- 9984945144002771
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