Caution When Diagnosing Your Mouse With Schizophrenia: The Use and Misuse of Model Animals for Understanding Psychiatric Disorders

Wong, Albert H.C.; Josselyn, Sheena A.

doi:10.1016/j.biopsych.2015.04.023

Cited by 47 publications

(32 citation statements)

References 91 publications

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“…The current consensus regarding animal models of psychiatric disorders is that no single model can completely recapitulate the full complexity of human conditions (Wong and Josselyn, 2015). As an example, auditory electrophysiological abnormalities recorded in studies involving the NR1-knockdown model are thought to more closely resemble those seen in autism than schizophrenia (Gandal et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Proteomic systems evaluation of the molecular validity of preclinical psychosis models compared to schizophrenia brain pathology

Cox

Gottschalk

Wesseling

et al. 2016

Schizophrenia Research

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Pharmacological and genetic rodent models of schizophrenia play an important role in the drug discovery pipeline, but quantifying the molecular similarity of such models with the underlying human pathophysiology has proved difficult. We developed a novel systems biology methodology for the direct comparison of anterior prefrontal cortex tissue from four established glutamatergic rodent models and schizophrenia patients, enabling the evaluation of which model displays the greatest similarity to schizophrenia across different pathophysiological characteristics of the disease. Liquid chromatography coupled tandem mass spectrometry (LC-MS) proteomic profiling was applied comparing healthy and "disease state" in human post-mortem samples and rodent brain tissue samples derived from models based on acute and chronic phencyclidine (PCP) treatment, ketamine treatment or NMDA receptor knockdown. Protein-protein interaction networks were constructed from significant abundance changes and enrichment analyses enabled the identification of five functional domains of the disease such as "development and differentiation", which were represented across all four rodent models and were thus subsequently used for cross-species comparison. Kernel-based machine learning techniques quantified that the chronic PCP model represented schizophrenia brain changes most closely for four of these functional domains. This is the first study aiming to quantify which rodent model recapitulates the neuropathological features of schizophrenia most closely, providing an indication of face validity as well as potential guidance in the refinement of construct and predictive validity. The methodology and findings presented here support recent efforts to overcome translational hurdles of preclinical psychiatric research by associating functional dimensions of behaviour with distinct biological processes.

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Section: Discussionmentioning

confidence: 99%

Proteomic systems evaluation of the molecular validity of preclinical psychosis models compared to schizophrenia brain pathology

Cox

Gottschalk

Wesseling

et al. 2016

Schizophrenia Research

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“…Although many investigators, including our group, provided review articles on DISC1 mouse models in the past (Brandon and Sawa, 2011; Wong and Josselyn, 2015), the present article will highlight recent findings that were not well covered in the previous reviews. Furthermore, an addition of novel DISC1 models for the past 3–4 years has enlarged our perspectives of how we can use these models to address biological questions in major mental illnesses in a valid manner.…”

Section: Introductionmentioning

confidence: 99%

Utility and validity of DISC1 mouse models in biological psychiatry

et al. 2016

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We have seen an era of explosive progress in translating neurobiology into etiological understanding of mental disorders for the past 10–15 years. The discovery of Disrupted-in-schizophrenia 1 (DISC1) gene was one of major driving forces that have contributed to the progress. The finding that DISC1 plays crucial roles in neurodevelopment and synapse regulation clearly underscored the utility and validity of DISC1-related biology in advancing our understanding of pathophysiological processes underlying psychiatric conditions. Despite recent genetic studies that failed to identify DISC1 as a risk gene for sporadic cases of schizophrenia, DISC1 mutant mice, coupled with various environmental stressors, have proven successful in satisfying face validity as models of a wide range of human psychiatric conditions. Investigating mental disorders using these models is expected to further contribute to the circuit-level understanding of the pathological mechanisms, as well as to the development of novel therapeutic strategies in the future.

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“…Nonetheless, numerous animal models exist for psychiatric diseases (for a review, see [62]) which can be highly informative to clinical context when their strengths and weaknesses are carefully considered [63]. However, similar to human studies, only a few animal models of psychiatric disorders have been the subject of investigation aiming at identifying the impact of adolescence exposure to alcohol on subsequent occurrence of psychiatric symptoms or syndromes.…”

Section: Late Psychiatric Consequences Of Adolescent Alcohol Consumptionmentioning

confidence: 99%

Comorbidity Between Psychiatric Diseases and Alcohol Use Disorders: Impact of Adolescent Alcohol Consumption

Jeanblanc

2015

Curr Addict Rep

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Patients suffering from psychiatric disorders such as schizophrenia and bipolar disorders often suffer from alcohol abuse or dependence. Conversely, most alcoholdependent patients suffer from other psychiatric disorders including depressive or anxiety disorders, with increased risk of suicide ideation and attempts. Adolescence is a crucial period of brain maturation but also of vulnerability to alcohol use disorders and other psychiatric diseases. While global alcohol consumption is decreasing in numerous Western countries, adolescent drinking is increasing with specific patterns of drinking called Bbinge drinking^leading to massive intoxication in a short period of time. Clinical and preclinical studies investigating the relationship between adolescent alcohol consumption and subsequent psychiatric disorders in patients or in animal models of psychiatric disorders will be described here and discussed.

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Caution When Diagnosing Your Mouse With Schizophrenia: The Use and Misuse of Model Animals for Understanding Psychiatric Disorders

Cited by 47 publications

References 91 publications

Proteomic systems evaluation of the molecular validity of preclinical psychosis models compared to schizophrenia brain pathology

Proteomic systems evaluation of the molecular validity of preclinical psychosis models compared to schizophrenia brain pathology

Utility and validity of DISC1 mouse models in biological psychiatry

Comorbidity Between Psychiatric Diseases and Alcohol Use Disorders: Impact of Adolescent Alcohol Consumption

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