Data were analyzed using the same model throughout (which controlled for ethnicity, IQ, pretreatment blood differential receptor gene expression, and baseline behavioral severity for each measure). All analyses tested for a main effect of treatment condition at the mean pretreatment blood AVP concentration. This LSM response takes into account any predictive effect of pretreatment blood AVP concentration on treatment response and gives an overall measure of efficacy in the population of participants as a whole. The ability of pretreatment blood AVP concentration to predict treatment response differentially in the drug-treated group is tested by the treatment condition–by–pretreatment blood AVP concentration interaction. Clinical Global Impression-Improvement (CGI-I) is a single score taken after a 4-week treatment. Otherwise, all other scores are given as a change from baseline, normalized for the direction of the scale, so that symptomatic improvement is reported as a positive change. For all measures, significant overall effects of treatment condition are in the predicted direction (i.e., AVP-treated participants improve more than placebo-treated participants). When a treatment condition–by–pretreatment blood AVP concentration interaction is significant, post hoc tests are reported for AVP-treated and placebo-treated participants: “Greater” indicates that symptomatic improvement increased with higher pretreatment blood concentrations of AVP; “Lesser” indicates that less improvement was observed at higher pretreatment blood concentrations of AVP; “ns” indicates that the scale was not significantly affected by pretreatment blood AVP concentrations. Subscales of an instrument are only tested if the overall score is significant at P < 0.05 and are tested at appropriate Bonferroni-corrected critical α to minimize the risk of false discovery. (Social Behavior Scale, 2nd Edition (SRS-2), critical α < 0.025; Repetitive Behaviors Scale-Revised (RBS-R), critical α < 0.0083). Any post hoc tests of treatment condition–by–pretreatment blood AVP concentration interactions are further Bonferroni-corrected to a critical α half that of the original critical α for the interaction. Effect sizes are given as ηp2. SCI, Social Communication and Interaction; RRB, Restricted Interests and Repetitive Behavior; CGI-S, Clinical Global Impression-Severity; FERT, Facial Emotion Recognition Test; RMET, Reading the Mind in the Eyes Test; NEPSY, Developmental NEuroPSYchological Assessment.
| Measure | Treatment condition main effect | Improvement in score LSM ± SE | *Significant after correction for multiple comparisons | Treatment condition– by–pretreatment blood AVP concentration interaction | *Significant after correction for multiple comparisons | Improvement in score becomes greater or lesser with higher pretreatment blood AVP concentrations | ||
| AVP | Placebo | AVP | Placebo | |||||
| Primary outcome measure | ||||||||
| SRS-2 T score | F1,20 = 9.853; P = 0.0052; ηp2 = 33.0% | 17.6 ± 1.37 | 10.8 ± 2.11 | * | F1,20 = 50.49; P < 0.0001; ηp2 = 71.6% | * | Greater | Lesser |
| SCI | F1,20 = 12.74; P = 0.0019; ηp2 = 38.9% | 17.5 ± 1.37 | 9.75 ± 2.11 | * | F1,20 = 58.38; P < 0.0001; ηp2 = 74.5% | * | Greater | Lesser |
| RRB | F1,20 = 1.045; P = 0.3188; ηp2 = 5.0% | 15.6 ± 1.73 | 12.7 ± 2.70 | ns | F1,20 = 7.601; P = 0.0122; ηp2 = 27.5% | * | Greater | ns |
| Secondary outcome measures (clinician-evaluated) | ||||||||
| CGI-S, social and communication | F1,20 = 0.549; P = 0.4674; ηp2 = 2.7% | 0.873 ± 0.126 | 0.712 ± 0.202 | ns | F1,20 = 1.519; P = 0.2320; ηp2 = 7.1% | ns | ||
| CGI-I, social and communication | F1,21 = 7.098; P = 0.0145; ηp2 = 25.3% | 2.23 ± 0.149 | 2.93 ± 0.244 | * | F1,21 = 9.520; P = 0.0056; ηp2 = 31.2% | * | Greater | ns |
| Secondary outcome measures (parent-rated) | ||||||||
| Spence Children’s Anxiety Scale | F1,20 = 9.014; P = 0.0070; ηp2 = 31.1% | 17.9 ± 1.66 | 9.14 ± 2.68 | * | F1,20 = 19.48; P = 0.0003; ηp2 = 49.3% | * | Greater | Lesser |
| RBS-R—total | F1,19 = 1.600; P = 0.2213; ηp2 = 7.8% | 17.2 ± 1.83 | 21.3 ± 3.18 | ns | F1,19 = 18.57; P = 0.0004; ηp2 = 49.4% | * | Greater | ns |
| Stereotypic | F1,19 = 0.001; P = 0.9783; ηp2 = 0.0% | 2.24 ± 0.313 | 2.23 ± 0.486 | ns | F1,19 = 4.932; P = 0.0381; ηp2 = 20.6% | ns | ||
| Self-injurious | F1,19 = 0.552; P = 0.4666; ηp2 = 2.8% | 0.594 ± 0.467 | 1.18 ± 0.828 | ns | F1,19 = 27.54; P < 0.0001; ηp2 = 59.2% | * | Greater | Lesser |
| Compulsive | F1,19 = 2.028; P = 0.1707; ηp2 = 9.6% | 3.35 ± 0.511 | 4.59 ± 0.819 | ns | F1,19 = 22.49 ; P = 0.0001; ηp2 = 54.2% | * | Greater | ns |
| Ritualistic | F1,19 = 3.133; P = 0.0920; ηp2 = 14.2% | 3.08 ± 0.504 | 4.63 ± 0.818 | ns | F1,19 = 3.643; P = 0.0708; ηp2 = 16.1% | ns | ||
| Sameness | F1,19 = 0.043; P = 0.8375; ηp2 = 0.2% | 5.61 ± 0.661 | 5.85 ± 1.03 | ns | F1,19 = 3.071; P = 0.0950; ηp2 = 13.9% | ns | ||
| Restricted | F1,19 = 0.623; P = 0.4392; ηp2 = 3.2% | 2.58 ± 0.54 | 3.4 ± 1.01 | ns | F1,19 = 4.261; P = 0.0522; ηp2 = 18.3% | ns | ||
| Secondary outcome measures (child performance) | ||||||||
| FERT | F1,7 = 10.85; P = 0.0132; ηp2 = 60.8% | 3.10 ± 2.42 | −7.19 ± 1.81 | * | F1,7 = 0.971; P = 0.3573; ηp2 = 12.2% | ns | ||
| RMET | F1,6 = 6.2341; P = 0.0467; ηp2 = 51.0% | 4.04 ± 1.63 | −1.28 ± 1.24 | * | F1,6 = 0.068; P = 0.8031; ηp2 = 1.1% | ns | ||
| NEPSY—Theory of Mind | F1,12 = 0.647; P =0.4367; ηp2= 5.1% | 2.1 ± 1.41 | 0.677 ± 1.20 | ns | F1,12 = 1.162; P =0.3022; ηp2= 8.8% | ns | ||
| NEPSY—Affect Recognition | F1,12 = 0.946; P = 0.3500; ηp2 = 7.3% | 0.094 ± 2.20 | −2.58 ± 1.90 | ns | F1,12 = 0.251; P = 0.6254; ηp2 = 2.0% | ns | ||