2.6 Statistical analyses
Potential sex and group differences in demographic and clinical characteristics were analyzed, such as ADHD symptoms, depression, anxiety, childhood trauma, and impulsivity. In case of significant effects for sex, group, or sex by group interactions, these outcome measures were included as confounders in follow-up exploratory analyses. Potential sex and group differences in subjective cue-reactivity (craving and affect) were analyzed using two repeated measures ANOVAs, with cue-type (cocaine vs neutral or emotional versus neutral) as repeated measures, group and sex as between group variable, and craving and negative affect as outcome variables. With regards to the assessment of affect during the cue reactivity paradigm, the current study asked for the participants rating in affect (a negative value represented a negative affect, a positive value reflects a positive affect). Negative or lower scores represent an increase in negative affect, while increases or positive scores represent an increase in positive affect.
Sex-dependent differences in negative emotional and cocaine cue activation of the ROIs was tested using repeated measures ANOVAs. More specifically, cue type (emotional cues versus neutral cues and cocaine cues versus neutral cues) was included as repeated measures in two separate analyses, group and sex as independent factors, and mean framewise displacement (FD) as covariate of non-interest. In case of significant sex by group by cue-type interaction effects, within group and sex follow-up tests were performed.
In order to investigate the moderating role of cocaine use characteristics on emotional and cocaine cue reactivity, several within CU group repeated measures analyses were performed, with cue type (emotional cues versus neutral cues and cocaine cues versus neutral cues) as repeated measure in two separate analyses, mean activation in the ROIs as dependent variable, sex as between group factor, and FD as covariate of non-interest. The following variables were included as covariates of interest, including years of regular cocaine use, age of onset of regular cocaine use, cocaine use severity (DUDIT-scores), and cocaine use per month in grams. In case of significant sex by covariate interaction effects, within sex follow-up tests were performed.
To test for main and interaction effects of group, sex and cue type outside the predefined ROIs, an exploratory whole-brain analysis was performed, with mean FD values for each subject as covariate of non-interest to account for potential motion differences. Whole brain analyses were family-wise error (FWE) rate corrected on cluster level (p < .05), with an initial height threshold on voxel level of p < .001.
The methods for analyzing the influence of menstrual phase and the use of hormonal contraceptives is described in the supplementary material.