Using animal models for the studies of schizophrenia and depression: The value of translational models for treatment and prevention

Animal models of psychiatric disorders have been highly effective in advancing the field, identifying circuits related to pathophysiology, and identifying novel therapeutic targets. In this review, we show how animal models, particularly those based on development, have provided essential informatio...

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Published inFrontiers in behavioral neuroscience Vol. 16; p. 935320
Main Authors Uliana, Daniela L., Zhu, Xiyu, Gomes, Felipe V., Grace, Anthony A.
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Research Foundation 24.08.2022
Frontiers Media S.A
Subjects
Adults
Amphetamines
Animal cognition
Animal models
Antipsychotics
Behavioral Neuroscience
Child development
Circuits
Clinical trials
Coping
depression
Dopamine
Drug development
Etiology
Executive function
Genetic engineering
Health risk assessment
hippocampus
Infections
Influenza
Mental depression
Mental disorders
Neurobiology
Pathophysiology
plasticity
prefrontal cortex
Psychosis
Psychotropic drugs
Schizophrenia
Social research
Therapeutic applications
Therapeutic targets
Validity
plasticity
depression
schizophrenia
hippocampus
dopamine
prefrontal cortex
Online AccessGet full text
ISSN1662-5153
1662-5153
DOI10.3389/fnbeh.2022.935320

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Abstract Animal models of psychiatric disorders have been highly effective in advancing the field, identifying circuits related to pathophysiology, and identifying novel therapeutic targets. In this review, we show how animal models, particularly those based on development, have provided essential information regarding circuits involved in disorders, disease progression, and novel targets for intervention and potentially prevention. Nonetheless, in recent years there has been a pushback, largely driven by the US National Institute of Mental Health (NIMH), to shift away from animal models and instead focus on circuits in normal subjects. This has been driven primarily from a lack of discovery of new effective therapeutic targets, and the failure of targets based on preclinical research to show efficacy. We discuss why animal models of complex disorders, when strongly cross-validated by clinical research, are essential to understand disease etiology as well as pathophysiology, and direct new drug discovery. Issues related to shortcomings in clinical trial design that confound translation from animal models as well as the failure to take patient pharmacological history into account are proposed to be a source of the failure of what are likely effective compounds from showing promise in clinical trials.
AbstractList Animal models of psychiatric disorders have been highly effective in advancing the field, identifying circuits related to pathophysiology, and identifying novel therapeutic targets. In this review, we show how animal models, particularly those based on development, have provided essential information regarding circuits involved in disorders, disease progression, and novel targets for intervention and potentially prevention. Nonetheless, in recent years there has been a pushback, largely driven by the US National Institute of Mental Health (NIMH), to shift away from animal models and instead focus on circuits in normal subjects. This has been driven primarily from a lack of discovery of new effective therapeutic targets, and the failure of targets based on preclinical research to show efficacy. We discuss why animal models of complex disorders, when strongly cross-validated by clinical research, are essential to understand disease etiology as well as pathophysiology, and direct new drug discovery. Issues related to shortcomings in clinical trial design that confound translation from animal models as well as the failure to take patient pharmacological history into account are proposed to be a source of the failure of what are likely effective compounds from showing promise in clinical trials.
Animal models of psychiatric disorders have been highly effective in advancing the field, identifying circuits related to pathophysiology, and identifying novel therapeutic targets. In this review, we show how animal models, particularly those based on development, have provided essential information regarding circuits involved in disorders, disease progression, and novel targets for intervention and potentially prevention. Nonetheless, in recent years there has been a pushback, largely driven by the US National Institute of Mental Health (NIMH), to shift away from animal models and instead focus on circuits in normal subjects. This has been driven primarily from a lack of discovery of new effective therapeutic targets, and the failure of targets based on preclinical research to show efficacy. We discuss why animal models of complex disorders, when strongly cross-validated by clinical research, are essential to understand disease etiology as well as pathophysiology, and direct new drug discovery. Issues related to shortcomings in clinical trial design that confound translation from animal models as well as the failure to take patient pharmacological history into account are proposed to be a source of the failure of what are likely effective compounds from showing promise in clinical trials.Animal models of psychiatric disorders have been highly effective in advancing the field, identifying circuits related to pathophysiology, and identifying novel therapeutic targets. In this review, we show how animal models, particularly those based on development, have provided essential information regarding circuits involved in disorders, disease progression, and novel targets for intervention and potentially prevention. Nonetheless, in recent years there has been a pushback, largely driven by the US National Institute of Mental Health (NIMH), to shift away from animal models and instead focus on circuits in normal subjects. This has been driven primarily from a lack of discovery of new effective therapeutic targets, and the failure of targets based on preclinical research to show efficacy. We discuss why animal models of complex disorders, when strongly cross-validated by clinical research, are essential to understand disease etiology as well as pathophysiology, and direct new drug discovery. Issues related to shortcomings in clinical trial design that confound translation from animal models as well as the failure to take patient pharmacological history into account are proposed to be a source of the failure of what are likely effective compounds from showing promise in clinical trials.
Author Zhu, Xiyu
Gomes, Felipe V.
Grace, Anthony A.
Uliana, Daniela L.
AuthorAffiliation 1 Department of Neuroscience, University of Pittsburgh , Pittsburgh, PA , United States
3 Department of Psychology, University of Pittsburgh , Pittsburgh, PA , United States
2 Department of Psychiatry, University of Pittsburgh , Pittsburgh, PA , United States
5 Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto , SP , Brazil
4 Department of Psychiatry and Behavioral Sciences, University of California, San Francisco , San Francisco, CA , United States
AuthorAffiliation_xml – name: 4 Department of Psychiatry and Behavioral Sciences, University of California, San Francisco , San Francisco, CA , United States
– name: 1 Department of Neuroscience, University of Pittsburgh , Pittsburgh, PA , United States
– name: 2 Department of Psychiatry, University of Pittsburgh , Pittsburgh, PA , United States
– name: 3 Department of Psychology, University of Pittsburgh , Pittsburgh, PA , United States
– name: 5 Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto , SP , Brazil
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  givenname: Daniela L.
  surname: Uliana
  fullname: Uliana, Daniela L.
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  surname: Zhu
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  surname: Gomes
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– sequence: 4
  givenname: Anthony A.
  surname: Grace
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Copyright © 2022 Uliana, Zhu, Gomes and Grace. 2022 Uliana, Zhu, Gomes and Grace
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Keywords plasticity
depression
schizophrenia
hippocampus
dopamine
prefrontal cortex
Language English
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SubjectTerms Adults
Amphetamines
Animal cognition
Animal models
Antipsychotics
Behavioral Neuroscience
Child development
Circuits
Clinical trials
Coping
depression
Dopamine
Drug development
Etiology
Executive function
Genetic engineering
Health risk assessment
hippocampus
Infections
Influenza
Mental depression
Mental disorders
Neurobiology
Pathophysiology
plasticity
prefrontal cortex
Psychosis
Psychotropic drugs
Schizophrenia
Social research
Therapeutic applications
Therapeutic targets
Validity
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Title Using animal models for the studies of schizophrenia and depression: The value of translational models for treatment and prevention
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Volume 16
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