Promoting social behavior with oxytocin in high-functioning autism spectrum disorders

Abstract

Social adaptation requires specific cognitive and emotional competences. Individuals with high-functioning autism or with Asperger syndrome cannot understand or engage in social situations despite preserved intellectual abilities. Recently, it has been suggested that oxytocin, a hormone known to promote mother-infant bonds, may be implicated in the social deficit of autism. We investigated the behavioral effects of oxytocin in 13 subjects with autism. In a simulated ball game where participants interacted with fictitious partners, we found that after oxytocin inhalation, patients exhibited stronger interactions with the most socially cooperative partner and reported enhanced feelings of trust and preference. Also, during free viewing of pictures of faces, oxytocin selectively increased patients' gazing time on the socially informative region of the face, namely the eyes. Thus, under oxytocin, patients respond more strongly to others and exhibit more appropriate social behavior and affect, suggesting a therapeutic potential of oxytocin through its action on a core dimension of autism.

Fig. 1.

Cyberball game and ball-toss distributions toward each of the three partners. (A) Schematic representation of the modified Cyberball game. On successive trials, the role of the participant P alternates between turns as observer of ball exchanges between two of the other players, as ball recipient, and as ball sender. The behavior of players A, B, and C is computer-generated so as to define three different profiles from P’s standpoint: an includer or good profile, a neutral profile, and an excluder or bad profile. The length of the gray arrows is proportional to the number of balls sent by a given player to each of the other players. The profiles represent the average behavior over the entire game but, rather than being fixed from the beginning, they were tuned progressively using an algorithm described in SI Text. Black arrows represent the behavior of a representative healthy subject. (B) Ball-toss distributions for healthy subjects and for patients with HF-ASD treated with oxytocin or placebo. Under oxytocin, there was a nearly significant trend in the number of balls sent toward the good as compared to the neutral player (significant trend, z = 1.82, P = 0.06; two-tailed) (middle) (mean and SEM; * indicates significant difference at P < 0.05 or better on posthoc pairwise comparisons).

Fig. 2.

Time course of ball tosses during the Cyberball game. Cumulative number of balls sent by the participant P to players A (good) and C (bad) in regularly spaced bins, for healthy subjects and for patients with HF-ASD under oxytocin and under placebo. Each data point falls in a bin defined by an interval between player A’s tosses n and n+2. The participant had, on average, three ball-toss opportunities in each interval. The transition in player A’s behavior from unbiased (equal probability of throwing the ball to each player) to positively biased toward P (100% probability of throwing the ball to P) was progressive (mean and SEM; * indicates significant difference at P < 0.05 or better for the first of two significant consecutive bins).

Fig. 3.

Subjective postexperimental rating under oxytocin and placebo treatment. Rating (1–7) of subjective feeling states toward the three players in the placebo and oxytocin-treated patients with HF-ASD (mean and SEM; * indicates significant difference at P < 0.05 or better on posthoc pairwise comparisons).

Fig. 4.

Mean gaze time spent on different regions of interest for patients with HF-ASD under placebo and oxytocin treatment. (A and B) Gaze time spent on the face and outside the face region under oxytocin and placebo when patients had to identify the face’s gender (male/female) and face’s gaze direction (direct/averted), respectively. (C and D) Gaze time spent on main regions of interest: the eyes, nose and mouth, and other regions such as forehead and cheeks during gender identification and gaze direction detection, respectively. * indicates significant difference at P < 0.05 or better on Wilcoxon test.