Sex differences in the development of emotion circuitry in adolescents at risk for substance abuse: a longitudinal fMRI study

Abstract

There is substantial evidence for behavioral sex differences in risk trajectories for alcohol and substance use, with internalizing factors such as negative affectivity contributing more to female risk. Because the neural development of emotion circuitry varies between males and females across adolescence, it represents a potential mechanism by which underlying neurobiology contributes to risk for substance use. Longitudinal functional magnetic resonance imaging was conducted in males and females (n = 18 each) with a family history of alcohol use disorders starting at ages 8–13 years. Participants performed an affective word task during functional magnetic resonance imaging at 1- to 2-year intervals, covering the age range of 8.5–17.6 years (3–4 scans per participant). Significant age-related sex differences were found in the right amygdala and right precentral gyrus for the negative vs neutral word condition. Males showed a significant decrease in both amygdala and precentral gyrus activation with age, whereas the response in females persisted. The subjective experience of internalizing symptomatology significantly increased with age for females but not for males. Taken together, these results reveal sex differences in negative affect processing in at-risk adolescents, and offer longitudinal neural evidence for female substance use risk through internalizing pathways.

Striatal alcohol cue‐reactivity is stronger in male than female problem drinkers

“…In this study, it was demonstrated that the alcohol pictures induced a stronger urge to drink in men compared to women, whereas women reported a stronger positive valence towards the nonalcoholic pictures, which could partly explain the reported sex differences in neural cue-reactivity. Moreover, the current findings also support the hypothesis that substance use and relapse in men is predominantly driven by external substance-related cues (positive reinforcement), whereas substance use and relapse in women is driven predominantly by internal negative emotional states (negative reinforcement) (Cosgrove et al, 2014;Hardee et al, 2017). In line with this, animal research demonstrated that corticosterone treatment, which is consistent with a mild physiological stressor, only induced alcohol-reinstatement in female but not in male rats (Bertholomey, Nagarajan, & Torregrossa, 2015).…”

Somatosensory function and pain in extremely preterm young adults from the UK EPICure cohort: sex-dependent differences and impact of neonatal surgery

“…decreased in males, increased in females). As sex-dependent differences in amygdala activation also emerge during adolescence, 59 , 60 divergence in thermal sensitivity between males and females may be clearer in early adulthood than at younger ages. Alterations in socio-emotional circuits, which are influenced by biological vulnerability, early life adversity, and parenting, have been proposed as a link between preterm birth and subsequent psychosocial and emotional outcomes, 56 and we suggest extending this model to include effects on experimental pain sensitivity in EP young adults.…”

Transdiagnostic neural correlates of volitional emotion regulation in anxiety and depression

“…As cognitive reappraisal engages a wide network of brain regions (Kohn et al, 2014;Messina et al, 2015;Wager, Davidson, Hughes, Lindquist, & Ochsner, 2008), the present results suggest that anxiety and depression are negatively associated with deficiencies recruiting a broader neural network. These regions are hypothesized to govern the behavioral output of reappraisal, as the SMA integrates input from frontal regions responsible for the formation of an internal representation of regulation goals with a behavioral response (Etkin et al, 2015), and the precentral gyrus governs internal emotional experiences that help guide motoric output (Hardee et al, 2017). These regions are hypothesized to govern the behavioral output of reappraisal, as the SMA integrates input from frontal regions responsible for the formation of an internal representation of regulation goals with a behavioral response (Etkin et al, 2015), and the precentral gyrus governs internal emotional experiences that help guide motoric output (Hardee et al, 2017).…”

“…Specifically, prior work confirms involvement of the SMA (Etkin, Büchel, & Gross, 2015;Kohn et al, 2014;Wager et al, 2008) and precentral gyrus (Picó-Pérez, Radua, Steward, Menchón, & Soriano-Mas, 2017) during reappraisal. These regions are hypothesized to govern the behavioral output of reappraisal, as the SMA integrates input from frontal regions responsible for the formation of an internal representation of regulation goals with a behavioral response (Etkin et al, 2015), and the precentral gyrus governs internal emotional experiences that help guide motoric output (Hardee et al, 2017). Although involvement of the cuneus during reappraisal is not well documented, this region is implicated in visual processing (Parker, Zalusky, & Kirbas, 2014).…”