Behaviourally inhibited temperament and female sex, two vulnerability factors for anxiety disorders, facilitate conditioned avoidance (also) in humans

Abstract

Acquisition and maintenance of avoidance behaviour is a key feature of all human anxiety disorders. Animal models have been useful in understanding how anxiety vulnerability could translate into avoidance learning. For example, behaviourally inhibited temperament and female sex, two vulnerability factors for clinical anxiety, are associated with faster acquisition of avoidance responses in rodents. However, to date, the translation of such empirical data to human populations has been limited since many features of animal avoidance paradigms are not typically captured in human research. Here, using a computer-based task that captures many features of rodent escape-avoidance learning paradigms, we investigated whether avoidance learning would be faster in humans with inhibited temperament and/or female sex and, if so, whether this facilitation would take the same form. Results showed that, as in rats, both vulnerability factors were associated with facilitated acquisition of avoidance behaviour in humans. Specifically, inhibited temperament was associated with higher rate of avoidance responding, while female sex was associated with longer avoidance duration. These findings strengthen the direct link between animal avoidance work and human anxiety vulnerability, further motivating the study of animal models while also providing a simple testbed for a direct human testing.

Keywords: Anxiety disorders; Associative learning; Avoidance learning; Behavioural inhibition; Female sex; Inbred Wistar–Kyoto rats; Translational research.

Figure 1

Computer-based escape-avoidance task. (A) An enemy spaceship appears in one of six locations on the screen, approximately every 1-s. The participant’s goal is to gain points by shooting and destroying this spaceship (1 point for each hit). (B) The warning and control signals (W+ and W−, respectively) are colored rectangles (pink and blue) in the top part of the screen, which appear in pseudorandom order, every 20-s, and remain visible for 5-s (the warning and control periods). (C) W+ is always followed by appearance of a bomb, which remains onscreen for 5-s (bomb period). The bomb period is divided into six segments of equal duration; during each segment there is an explosion and loss of 5 points to a maximum of 30 points. (D) Moving to a “safe area” during the bomb period stops point loss (ER), while moving to a safe area during the warning period and remaining there through the rest of the warning period and through the subsequent bomb period prevents any point loss (AR). Labels shown in white text are for illustration only and do not appear on the screen during the task.

Figure 2

Hiding duration, defined as number of segments during which the participant exhibited full hiding on each trial. (A) Hiding duration during the warning period, control period, and bomb period. Analyses revealed a main effect of trial, as well as differences between all the three periods starting from the fourth trial (all p<0.001) (B) Hiding duration during warning period and bomb period in inhibited (dashed curve; n=49) vs. uninhibited (dotted curve; n=46) participants, based on median split value on HA (median=12). Hiding during the control period was minimal in both groups and was omitted from this graph for clarity. Hiding duration during the warning period could be predicted by inhibited temperament (stepwise linear regression, p=0.024). Error bars indicate SEM.

Figure 3

AR duration, defined as the number of warning period segments during which the participant exhibited full hiding, across trials where an AR was demonstrated (i.e., no points were lost), in females (left; n=36) vs. males (right; n=27). AR duration could be predicted by sex (stepwise linear regression, p=0.015). Error bars indicate SEM.