Anxiety Assessment in Pre-clinical Tests and in Clinical Trials: A Critical Review

Abstract

The identification of anxious symptoms is crucial to diagnose anxiety disorders, as well as to monitor their treatment in clinical practice and research. The aim of this review is to discuss the different ways of assessing anxiety in clinical research, including clinical trials, and the different kinds of animal behavioral tests used to study anxiety and test the efficacy of anxiolytics in pre-clinical studies. In clinical practice, a categorical classification (such as the Diagnostic and Statistical Manual of Mental Disorders and the International Statistical Classification of Diseases and Related Health Problems) distinguishes the cases of the disease versus non-disease. Some structured and semi-structured interviews can be used to arrive at these diagnoses. On the other hand, anxiety can also be assessed using a dimensional approach, through self-report or hetero-evaluation questionnaires. Regarding the assessment of anxiety in animals, several behavioral tests are described and evaluated, namely the Social Interaction Test, Elevated Plus Maze and Open Field Test. Under a critical view, these two approaches are presented and discussed, in order to improve the outcome of research in this field.

Intrathecal Oxytocin Improves Spontaneous Behavior and Reduces Mechanical Hypersensitivity in a Rat Model of Postoperative Pain

“…As shown in Figure 3A (inferior panels), we found that during the exploratory hour, untreated surgery animals spent less time (p ≤ 0.015) in the center of the cage, but this behavior was not observed in animals treated with oxytocin (p = 0.929). Certainly, under light conditions, anxious animals tend to exhibit minimal exploratory behavior; thus, spending less time in the center is predictable (Castanheira et al, 2018). Accordingly, during the dark phase we did not find a substantial statistical effect before and after surgery, although a slight increase in this variable was observed in the oxytocin-treated animals (p = 0.073).…”

“…In all cases we measured the horizontal activity (total distance), vertical episodes (rearing), and time (seconds) spent in the center of the open-field system. Indeed, horizontal and vertical activity have been proposed as an endpoint to indirectly analyze potential analgesic compounds ( Imanaka et al., 2008 ; Majuta et al., 2017a ), whereas time spent in the center has been used as an endpoint to analyze anxiety-related effects ( File, 1980 ; Castanheira et al., 2018 ), a key issue after postoperative pain ( Carr and Goudas, 1999 ; Kehlet and Dahl, 2003 ; Kouya et al., 2015 ).…”

Low-concentration sevoflurane inhalation in treating MK801-induced schizophrenia like disease in mice and a feasibility study of schizophrenia patients

“…We found that 1-hour 1% sevo urane inhalation for 5 days reversed the decreases in locomotion and sociability induced by MK801. OFT was adopted to access the exploratory behaviors and emotional disorders including anxiety-like and depression-like behaviors 19,20 , whilst an automated three-chambered social approach task was used for evaluating sociability 21 . Our results are in agreement with studies showing that administration of MK801 to neonatal animals induced reduction in spontaneous locomotor activity in long-term which may re ect psychomotor retardation 22,23,24 .…”

The Neuroprotective Action of Amidated-Kyotorphin on Amyloid β Peptide-Induced Alzheimer’s Disease Pathophysiology

“…The OFT is widely used to assess individual spontaneous locomotor activity and anxiety-like behavior when animals are introduced to a novel environment ( Prut and Belzung, 2003 ; Bailey and Crawley, 2009 ; Castanheira et al., 2018 ). Importantly, this test allows to detect bias in animal behaviour that could affect performance on NORT, since locomotor activity can impact exploratory drive ( Broadhurst, 1957 ; Broadhurst, 1958 ).…”