Role of murine models in psychiatric illness drug discovery: a dimensional view

Hoffman, Kurt L.

doi:10.1517/17460441.2013.797959

Cited by 12 publications

(4 citation statements)

References 97 publications

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“…86 No. 6 2021 depression [54], together with our own data, allowed us to suggest a plausible neurochemical mechanism underlying these disruptions in the mixed anxiety depressive disorder [55,56] (figure).…”

Section: Mental Disordersmentioning

confidence: 82%

Monoamine Oxidase as a Potential Biomarker of the Efficacy of Treatment of Mental Disorders

Узбеков

2021

Biochemistry Moscow

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The review summarizes the results of our own studies and published data on the biological markers of psychiatric disorders, with special emphasis on the activity of platelet monoamine oxidase. Pharmacotherapy studies in patients with the mixed anxiety-depressive disorder and first episode of schizophrenia have shown that the activity of platelet monoamine oxidase could serve as a potential biomarker of the efficacy of therapeutic interventions in these diseases.

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Section: Mental Disordersmentioning

confidence: 82%

Monoamine Oxidase as a Potential Biomarker of the Efficacy of Treatment of Mental Disorders

Узбеков

2021

Biochemistry Moscow

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“…Schizophrenia-relevant behaviour: Schizophrenia-like behaviour can be modelled in rodents using tests to assess positive and negative symptoms, as well as cognitive impairment and sensorimotor gating deficits. These are described above in section 1.3 (reviews: [24,41,42]).…”

Section: Definitionsmentioning

confidence: 99%

Schizophrenia and drug addiction comorbidity: recent advances in our understanding of behavioural susceptibility and neural mechanisms

Menne

Chesworth

2020

Neuroanatomy and Behaviour

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Schizophrenia is a severe psychiatric disorder which is worsened substantially by substance abuse/addiction. Substance abuse affects nearly 50% of individuals with schizophrenia, extends across several drug classes (e.g. nicotine, cannabinoids, ethanol, psychostimulants) and worsens overall functioning of patients. Prominent theories explaining schizophrenia and addiction comorbidity include the primary addiction hypothesis (i.e. schizophrenia susceptibility primes drug reward circuits, increasing drug addiction risk following drug exposure), the two-hit hypothesis (i.e. drug abuse and other genetic and/or environmental risk factors contribute to schizophrenia development) and the self-medication hypothesis (i.e. drug use alleviates schizophrenia symptoms). Animal models can be used to evaluate the utility and validity of these theories. Since this literature was last reviewed by Ng and colleagues in 2013 [Neurosci Biobehav Rev, 37(5)], significant advances have been made to our understanding of schizophrenia and substance abuse comorbidity. Here we review advances in the field since 2013, focussing on two key questions: 1) Does schizophrenia susceptibility increase susceptibility to drug addiction (assessing the primary addiction hypothesis), and 2) Do abused drugs exacerbate or ameliorate schizophrenia symptoms (assessing the two-hit hypothesis and the self-medication hypothesis). We addressed these questions using data from several schizophrenia preclinical models (e.g. genetic, lesion, neurodevelopmental, pharmacological) across drug classes (e.g. nicotine, cannabinoids, ethanol, psychostimulants). We conclude that addiction-like behaviour is present in several preclinical schizophrenia models, and drugs of abuse can exacerbate but also ameliorate schizophrenia-relevant behaviours. These behavioural changes are associated with altered receptor system function (e.g. dopaminergic, glutamatergic, GABAergic) critically implicated in schizophrenia and addiction pathology.

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“…It has been argued that new preclinical models should focus on a dimensional construct and domains of psychopathology, which do not conform to the nosological categories and are consistent with increasing evidence of genetic, environmental and biological commonality between schizophrenia, bipolar disorder and other psychiatric disorders (O’Tuathaigh and Waddington, 2015). This approach is anticipated to shed more light on mental disorders as varying constellations of functional domains and will advance our knowledge of the neurobiology of basic processes that transcend diagnostic boundaries and are based on measurable phenotypes easily translatable across different species and more amenable to future biology-driven treatment (Petrinovic and Künnecke, 2014; Hoffman, 2013; Argyropoulos et al, 2013; Mahoney and Olmstead, 2013; Cuthbert, 2014). For example, Fig 1 depicts as different combinations of the same genetic and environmental risk factors result in varying phenotypic domains impertinent to the specific nosological category.…”

Section: Future Prospectsmentioning

confidence: 99%

Animal models of gene–environment interaction in schizophrenia: A dimensional perspective

Ayhan

McFarland

Pletnikov

2016

Progress in Neurobiology

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Schizophrenia has long been considered as a disorder with multifactorial origins. Recent discoveries have advanced our understanding of the genetic architecture of the disease. However, even with the increase of identified risk variants, heritability estimates suggest an important contribution of non-genetic factors. Various environmental risk factors have been proposed to play a role in the etiopathogenesis of schizophrenia. These include season of birth, maternal infections, obstetric complications, adverse events at early childhood, and drug abuse. Despite the progress in identification of genetic and environmental risk factors, we still have a limited understanding of the mechanisms whereby gene-environment interactions (GxE) operate in schizophrenia and psychoses at large. In this review we provide a critical analysis of current animal models of GxE relevant to psychotic disorders and propose that dimensional perspective will advance our understanding of the complex mechanisms of these disorders.

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Role of murine models in psychiatric illness drug discovery: a dimensional view

Cited by 12 publications

References 97 publications

Monoamine Oxidase as a Potential Biomarker of the Efficacy of Treatment of Mental Disorders

Monoamine Oxidase as a Potential Biomarker of the Efficacy of Treatment of Mental Disorders

Schizophrenia and drug addiction comorbidity: recent advances in our understanding of behavioural susceptibility and neural mechanisms

Animal models of gene–environment interaction in schizophrenia: A dimensional perspective

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