**1.4 Symptoms versus endophenotypes in experimental model animals**

There is a consensus about the low reliability of the diagnostic construct provided for the employment of Diagnostic and Statistical Manual of Mental Disorders or DMS (which is a manual that determines the criteria for the clinical diagnosis of PDs). The heterogeneity implicit in this classification system and the imprecise quantification of the symptoms make it impossible to deconstruct PDs within model organisms. In fact, an etiology-based nosology system has been advocate for psychiatry, and it has been proposed to identify the endophenotypes that occur in both healthy individuals and subjects with different psychopathologies [14]. Endophenotypes are basically quantitative trait-like deficits that are possible to assess by laboratory-based methods rather than by clinical observation. An endophenotype should be state-independent, heritable, occurring at a high rate in affected families, and in addition, it should be associated to genetic variants of the disorder, as it should be involved the same brain circuits associated with the symptoms of the illness in patients (**Table 1**).

The Research Domains Criteria (RDoC) framework was introduced as an alternative categorization system for psychopathological states [15–17]. This system provides a platform to improve the translatability of studies from animals to humans, since it supports the endophenotype-based comparison of animals and humans on an objective neurobiological basis across all behavioral domains. In fact, the endophenotypes have been reverse-translated into animal models successfully and allows the evaluation


**Table 1.**

*Most common endophenotypes used to evaluate behaviors associated with psychiatric disorders (PDs).*

of the neural neurobiological substrates and their circuit dysfunctions [18]. Thus, it has been demonstrated that the modeling of neurobiological and behavioral endophenotypes to reproduce PDs in experimental animals is possible.

The ideal animal model should be derived from risk factors or the causative agent of the human disease. One of the strategies used during the construction of a model is focused on a specific factor that can reproduce the condition as a whole or an aspect of the disease [19]. The choice for the methodology used in establishing a model is fundamentally important to guide which aspect of the disease should be explored, and it is an essential component in the validation of a model known as construct validity.

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*Animal Models in Psychiatric Disorder Studies DOI: http://dx.doi.org/10.5772/intechopen.89034*

observed in behavioral and molecular levels.

**2.1 Animal models in schizophrenia (SCZ)**

In the following sections, selected examples of animal models used in the context of investigating PDs will be demonstrated, indicating which changes are

Schizophrenia (SCZ) is a severe brain disorder, characterized by a set of positive and negative symptoms and cognitive disorders, which are the basis for the clinical diagnosis of individuals who needs to present at least two or more of those symptoms, according to the DSM. SCZ is one of the most debilitating mental disorders, affecting about 21 million people worldwide. The antipsychotics used to treat SCZ patients can soften the development of the disorder, and this pharmacological treatment was the basis for the most accepted theory to explain the neurobiology of SCZ, as noticed by the alterations in the dopamine transmission. In addition, several other theories have been suggested soon after, as for instance, the serotoninergic, glutamatergic, GABAergic, and the neurodevelopmental susceptibility hypothesis, among others [20]. However, none of these theories had allowed the characterization of the etiology or the identification of strong biomarker for the diagnosis of SCZ. Many efforts are being made to characterize a model for SCZ, but there is a great difficulty in reproduce endophenotypes that frame all the groups of symptoms related to this disease, or which allow associating all risk factors that are already known. Below, we exemplify some of these models, and for a more detailed review of SCZ models can be

Most of the models are based on the theory of neurotransmitter imbalance, and they are induced by the disruption of these pathways, other models explore changes in the levels of expression of candidate genes involved in the processes of SCZ susceptibility. It should be considered that SCZ is a multifactorial disorder, and thus, the genetic component should be evaluated in addition to changes in the environment, as in contrast to the models based on genetic alterations, there are those taking into account the environmental changes, such as the prenatal insults, which impose changes in the neurodevelopment processes. Some of these models

All of these models show behavioral and molecular changes that can be associ-

Major depressive disorder (MDD) is a common, complex, and heterogeneous mental disorder, characterized by persistent sadness and loss of interest in general activities, affecting about 10% of the population worldwide, and which is caused by multifactorial mechanisms not fully understood yet, characterizing MDD as a disorder with many variations in clinical features among the patients, imposing a consequent high variability in the diagnosis, time course of response and remission [45], which is one of the main reasons justifying the intensive search for animal models and biomarkers, aiming for advances in MDD diagnosis [46]. In addition, these advances could be helpful for a better classification for depressive spectrum, and thereby for improving the treatment [47]. The animal models of depression have been developed based on acute or chronic stress exposure, exogenous administration of glucocorticoids, injuries in brain regions and/or genetic manipulations [48–50]. There is a great variation in the number of protocols that

**2.2 Animal models in major depressive disorder (MDD)**

**2. PDs and animal models**

found elsewhere [21].

are exemplified in **Table 2**.

ated with SCZ.
