Psychiatric Pathology and Its Challenges
It is well known to all that accurate pathological research not only provides evidence for disease diagnosis but also is full of opportunities for potential target discovery and novel efficient treatment development. The exploration of pathological mechanisms and the development of novel therapeutics for neurological diseases have always been one of the most challenges due to the high complexity of the central nervous system. However, compared with the progress in the pathogenesis and new target identification of neurodegenerative diseases, the understanding and exploration of the pathology of psychiatric disorders lag far behind.
Unlike other indications which mainly involve molecular pathological mechanisms, the pathology of psychiatric disorders mainly involves multiple aspects, such as pathophysiology (molecular pathology) and some psychologies. Moreover, pathophysiology studies for psychiatric disorders are more challenging compared with other neurological diseases.
-
The first is that psychiatric disorders are relatively abstract mainly involving the level of thought and consciousness. It is difficult to identify the relevant “pathogenic” genes and link genomic alterations with molecular and cellular changes.
-
The diagnosis of psychiatric disorders needs to be improved by defining the molecular, cellular, and biochemical changes associated with each disease pathophysiology, which is currently primarily diagnosed through behaviors.
-
Psychiatric disorder animal modeling (traditional modeling by symptoms) is challenging and there is a great difference between modeling animals and humans.
Animal Modeling of Disease Pathology for Target Identification and Verification
Pathological mechanisms or biomedical research of psychiatric disorders is a highly complicated process, which needs useful tools that can imitate the complexity of the human neural pathways and behaviors. Animal models that attempt to replicate the disease processes remain irreplaceable tools for psychiatric pathological research, target identification, and novel treatment discovery. In recent years, the emergence and development of humanized mice and genetically engineering animals makes psychiatric modeling no longer limited to the traditional behavior-based induction modeling. Animal modeling even can be extremely similar to human psychiatric disorders at the genetic or molecular level, which plays a significant role in the identification and validation of potential targets and the development of new therapeutic strategies for human psychiatric pathologies.
Over the past decades of years, multiple candidate genes have been screened as risk genes for psychiatric disorders during psychiatric modeling in rodents and nonhuman primates. For example, photo-genetics research of the activation of the neuronal pathway using transgenic animals provides a clue for investigating the mechanism for selective activation of cholinergic, GABAergic, and glutamatergic neurons in amygdala and striatum may modulate endophenotypes in transgenic animals carrying different psychiatric risk genes, and also offers opportunities for potential target identification and validation.
For Research Use Only.
