Borderline personality disorder (BPD) is characterized by disadvantageous decisions that are often expressed in close relationships and associated with intense negative emotions. Although functional neuroimaging studies of BPD have described regions associated with altered social cognition and emotion processing, these correlates do not inform an understanding of how brain activity leads to maladaptive choices. Drawing on recent research, we argue that formal models of decision-making are crucial to elaborating theories of BPD that bridge psychological constructs, behavior, and neural systems. We propose that maladaptive interactions between Pavlovian and instrumental influences play a crucial role in the expression of interpersonal problems. Finally, we articulate specific hypotheses about how clinical features of BPD may map onto neural systems that implement separable decision processes.

Dimensional approaches to psychiatric nosology are rapidly transforming the way researchers and clinicians conceptualize personality pathology, leading to a growing interest in describing how individuals differ from one another. Yet, in order to successfully prevent and treat personality pathology, it is also necessary to explain the sources of these individual differences. The emerging field of personality neuroscience is well-positioned to guide the transition from description to explanation within personality pathology research. However, establishing comprehensive, mechanistic accounts of personality pathology will require personality neuroscientists to move beyond atheoretical studies that link trait differences to neural correlates without considering the algorithmic processes that are carried out by those correlates. We highlight some of the dangers we see in overpopulating personality neuroscience with brain-trait associational studies and offer a series of recommendations for personality neuroscientists seeking to build explanatory theories of personality pathology.

The vacuolar H+-ATPase (V-ATPase) is an enzymatic complex that functions in an ATP-dependent manner to pump protons across membranes and acidify organelles, thereby creating the proton/pH gradient required for membrane trafficking by several different types of transporters. We describe heterozygous point variants in ATP6V0C, encoding the c-subunit in the membrane bound integral domain of the V-ATPase, in 27 patients with neurodevelopmental abnormalities with or without epilepsy. Corpus callosum hypoplasia and cardiac abnormalities were also present in some patients. In silico modeling suggested that the patient variants interfere with the interactions between the ATP6V0C and ATP6V0A subunits during ATP hydrolysis. Consistent with decreased V-ATPase activity, functional analyses conducted in Saccharomyces cerevisiae revealed reduced LysoSensor fluorescence and reduced growth in media containing varying concentrations of CaCl2. Knockdown of ATP6V0C in Drosophila resulted in increased duration of seizure-like behavior, and the expression of selected patient variants in Caenorhabditis elegans led to reduced growth, motor dysfunction, and reduced lifespan. In summary, this study establishes ATP6V0C as an important disease gene, describes the clinical features of the associated neurodevelopmental disorder, and provides insight into disease mechanisms.

Individuals with personality disorders often experience romantic relationship dysfunction and have an insecure attachment style. Here, we examined attachment dynamics in dyadic interactions, focusing specifically on the role of physiological coregulation in state attachment processes in couples oversampled for personality pathology. A total of 121 couples completed a 10-minute discussion about an area of disagreement in their relationship and a 5-minute discussion in which they planned an event together. We used a dynamical model of heart rate changes to estimate coregulation. We found that (a) increases in state attachment avoidance were associated with contrarian coregulation (heart rate becoming misaligned with the partner's physiology) and (b) conversely, increases in state attachment anxiety were associated with dependent coregulation (heart rate becoming aligned with the partners' physiology). Dispositional attachment insecurity moderated the effects of state attachment insecurity on physiological coregulation. Whereas dispositional anxiety predicted individuals exhibiting dependent coregulation in response to state insecurity, dispositional avoidance predicted contrarian coregulation in response to state insecurity. This work provides insight into the role of physiological coregulation in attachment dynamics among couples oversampled for personality pathology, suggesting that disruptions to coregulation contribute to impaired emotion regulation during romantic conflicts.

Personality pathology is associated with dysfunctional romantic relationships. This study found that disruptions to physiological attunement during conflict predict short-term discord and long-term relationship dysfunction in couples affected by personality pathology.