Exposure to early adverse life events has been related to multiple psychological and physical outcomes (Lopez et al., 2021; Norman et al., 2012), including abnormalities in brain structure (Crossley et al., 2019; Smith and Pollak 2020; Zugman et al., 2023). Thus, cumulative adversity in the form of physical, sexual, and emotional abuse and neglect has been associated with changes in prefrontal cortex (PFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), insula, amygdala (AMY), hippocampus (HIPP), and parahippocampus volumes (Ansell et al., 2012; Lim et al., 2014; Papagni et al., 2011; Ringwald et al., 2022). Several of these regions are associated with emotion regulation (ER) (Korgaonkar et al., 2013). In addition, adverse childhood experiences (ACEs), as stressful and/or traumatic events that occur during a critical period, have a distinct effect on neurodevelopment (Zarei et al., 2021), thus influencing the maturation of circuits that regulate emotion, self-control, and top-down processing (Ansell et al., 2012; Korgaonkar et al., 2013; Tyborowska et al., 2018). In this manner, although genetic predisposition may modulate the direction or strength of its imprint (Clausen et al., 2019; Popovic et al., 2020; Teicher et al., 2016), childhood adversity leads to increased risk of psychiatric disorders (Amad et al., 2014; Chapman et al., 2004; O'Neill et al., 2012; Vatheuer et al., 2021), at least in part, by disrupting ER (Yuan et al., 2023).

ER has even been proposed as a transdiagnostic mechanism linking childhood maltreatment to psychopathology (Weissman et al., 2019). Both Borderline Personality Disorder (BPD) and Major Depressive Disorder (MDD) are clinical disturbances characterized by emotion dysregulation and negative affectivity (Ebneabbasi et al., 2021; Fernando et al., 2023), and both have been associated with exposure to ACEs (Yuan et al., 2023; Wang et al., 2023). These disorders, in turn, have been associated with structural changes of regions that comprise ER brain circuits, including the ACC, OFC, ventrolateral and dorsolateral PFC (vl/dlPFC), HIPP, and AMY (Bøen et al., 2014; Bora et al., 2012; Lei et al., 2019; Nolan et al., 2020; Ruocco et al., 2012; Suh et al., 2019; Yang et al., 2016).

MDD patients exposed to severe early life stressors have been shown to have reductions in the HIPP, AMY (Aghamohammadi-Sereshki et al., 2021; Weissman et al., 2020), ACC, dlPFC (Kim et al., 2019a), OFC (Monninger et al., 2020; Ringwald et al., 2021), and insular cortex (Saleh et al., 2017). Severity of childhood maltreatment was also associated with cortical thinning in temporo-parietal regions compared to participants not exposed to ACEs (Tozzi et al., 2020). In turn, BPD patients with a history of childhood abuse showed a reduced volume of the vlPFC (Morandotti et al., 2013) and HIPP (Brambilla et al., 2004) compared to those without this risk factor.

Nonetheless, it is unclear how much MDD and BPD share in terms of the effects of ACEs on brain structure. Our group and others have documented significant neurobiological differences between MDD and BPD in spite of shared symptoms (e.g., affective dysregulation, sadness, self-injurious behavior) and significant comorbidity (Villarreal et al., 2021; Cao et al., 2022). Further, ACEs association with BPD (Porter et al., 2020) is stronger than that assigned to MDD (Nemeroff et al., 2020; Zisook et al., 2022). Our hypothesis proposes that ACEs have a greater impact on cortical and subcortical structures for the BPD group as compared to the MDD group, which leads us to predict a more significant reduction of brain regions involved in ER for the former. To test this hypothesis, we studied the impact of ACEs on the volume of subcortical structures and cortical thickness in comparable groups of outpatients with either BPD or MDD.