What is Back Translation?
Back translation usually refers to the reduction of the translated or the target document back into the original source language, which allows a comparison of quality and accuracy between the translated and the original. The back translation method is helpful for the identification of nuances and the improvement of translation. It has been widely used as a quality assessment tool for cross-cultural psychology research, educational assessment, and quality of life research over the past several decades. In the field of drug discovery, back translation, also known as reverse translation, is a method of translating the clinical data or clinical results back to the pre-clinical biological and pharmacological research, which is so-called “bedside to bench”. It has emerged as a useful approach for neurophysiological and drug development in central nervous system disorders, especially in psychiatric disorders.
The Role of Back Translation in Psychiatric Disorders
Psychiatric disorders, also known as mental disorders or psychosis, are neurological diseases manifested by abnormalities or dysfunctions in thoughts, cognition, emotion, and behaviors. For most psychiatric disorders, the Food and Drug Administration (FDA)-approved drugs or treatments are still very limited. The drug development of neurological diseases, particularly in psychiatry, is challenging and full of contingency. For example, drugs for depression or schizophrenia, such as promethazine and thymidine were accidentally found to be effective on psychiatric symptoms during the initial development for the treatment of tuberculosis and antihistamines respectively. These “accidental” drugs have not been tested in animal models of antidepressants or antipsychotics, nor have they been subjected to rigorous, double-blind, placebo-controlled trials, but prompted scientists that identifying potential reactive psychiatric targets based on the approach of reverse translation. Currently, reverse translation, or patient-based translation, is a valuable method for psychiatric target identification and validation, which enables target identification based on known clinical results.
Examples for Target Identification and Verification Through Back Translation
Currently, preclinical animal models with knowing neurophysiological and pharmacological effects of drugs have played an important role in the development of new therapies for psychiatric disorders based on the back translation. Back translation using psychiatric animal models enables a rapid of screening new compounds and identification of the targets that respond to identified targets.
A typical example is the discovery of the antidepressant iproniazid, which was found by chance during the treatment of tuberculosis patients (Wong, 2000). Shortly after this clinical discovery, it has been demonstrated based on animal models that the antibiotic iproniazid exerted antidepressant activity by inhibiting the activity of monoamine oxidase to slow down the breakdown of norepinephrine 5-hydroxytryptamine and dopamine. Moreover, the development of modern transgenic animal models with obvious and featured human psychiatric symptoms also has greatly promoted and encouraged potential target identification and verification through the forward pharmacology method. In the several decades since then, the discovery and identification of psychiatric targets mainly rely on forward pharmacology.
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