Seventy-four healthy volunteers were included in this study (25 men and 49 women, mean age 20 ± 3.0 years). Five participants were current cigarette smokers (4 women, 1 man); none of the participants had any Axis I psychiatric disorders. Participants were recruited from community advertisements (n = 25) or from one of three longitudinal cohorts (Quebec Study of Newborn Twins, n = 5, and two cohorts from the Quebec Longitudinal Study of Child Development, n = 44). In the case of twins, only a single volunteer per twin pair was included. The study was carried out in accordance with the Declaration of Helsinki and approved by the Research Ethics Board of the Montreal Neurological Institute, McGill University, the ethics committee of the CHU Sainte-Justine Research Center, and the ethics committe of the Institut de la Statistique du Quebec. All participants provided written informed consent.
For female participants, menstrual phase at the time of the scan was determined based on the date of last menstrual period and length of cycle (self-report). Serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured in a subset of participants (n = 10) to confirm this. Of women not using hormonal contraception (n = 29), the majority (n = 21) were tested during the follicular phase, five during the luteal phase, and three during ovulation.
PET scans were acquired between 10 am and 3 pm using a high-resolution research tomograph (HRRT, CTI/Siemens). Prior to injection of the ligand, a 6-min transmission scan was performed with 137Cs to correct for tissue attenuation. Subsequently, a 60-min dynamic scan was initiated concurrent with the beginning of a one-minute bolus injection of 370 MBq [11C]ABP688. Dynamic data were collected with the scanner in list mode and reconstructed using an ordered subset maximization algorithm including motion correction to the transmission scan. High-resolution (1 mm3) T1-weighted anatomical magnetic resonance imaging (MRI) scans were acquired using a 1.5 T Siemens Sonata scanner (gradient echo pulse sequence, repetition time = 9.7 ms, echo time = 4 ms, flip angle = 12°, field of view = 250 mm and matrix = 256 × 256) or a 3 T Siemens Trio TIM scanner (MPRAGE sequence, repetition time = 2300 ms, echo time = 3.42 ms, flip angle = 9°, field of view = 256 mm and matrix = 256 × 256).
Regions of interest (ROIs) were defined using standard masks on the MNI152 template then registered to individual PET images. The ROIs included three prefrontal cortex subregions (orbitofrontal, dorsolateral, and medial), three functional striatum subregions (associative, sensorimotor and ventral), insula, hippocampus, and amygdala. Regional non-displaceable binding potential values (BPND) were extracted from each ROI using the simplified reference tissue model with cerebellar grey matter as the reference tissue. Scan start times were compared between men and women using independent samples t tests. Percent (E)-isomer content and injected tracer mass were compared using the Wilcoxon rank sum test due to their non-normal distribution. The effect of sex on BPND values was analyzed using repeated measures analysis of covariance (ANCOVA) with region as a repeated measure, sex as a between subject factor, and tracer (Z)-isomer content and smoking status as covariates. Post-hoc independent samples t-tests were then performed within each ROI. Whole brain voxel-wise analyses of BPND were compared using SPM12 (Wellcome Functional Imaging Laboratory). Summary BPND values were computed as the unweighted mean of all examined regions. One-way ANOVA was used to assess the effect of menstrual phase on BPND. In exploratory analyses, correlations between summary BPND and serum LH or FSH levels were assessed using Pearson’s r.