The subgenual anterior cingulate cortex (subgenual ACC) plays an important role in regulating emotion, and degeneration in this area correlates with depressed mood and anhedonia. Despite this understanding, it remains unknown how this part of the prefrontal cortex causally contributes to emotion, especially positive emotions. Using Pavlovian conditioning procedures in macaque monkeys, we examined the contribution of the subgenual ACC to autonomic arousal associated with positive emotional events. After such conditioning, autonomic arousal increases in response to cues that predict rewards, and monkeys maintain this heightened state of arousal during an interval before reward delivery. Here we show that although monkeys with lesions of the subgenual ACC show the initial, cue-evoked arousal, they fail to sustain a high level of arousal until the anticipated reward is delivered. Control procedures showed that this impairment did not result from differences in autonomic responses to reward delivery alone, an inability to learn the association between cues and rewards, or to alterations in the light reflex. Our data indicate that the subgenual ACC may contribute to positive affect by sustaining arousal in anticipation of positive emotional events. A failure to maintain positive affect for expected pleasurable events could provide insight into the pathophysiology of psychological disorders in which negative emotions dominate a patient's affective experience.Area 25 | infralimbic | pupil size | anticipatory arousal T he ability to regulate emotion and arousal in response to pleasurable and aversive situations is essential for adapting to our environment and, ultimately, for our mental health. The anterior cingulate cortex (ACC), specifically its subgenual part, has been implicated in a number of psychiatric disorders, including major depressive disorder (1). Dysfunction and degeneration in the subgenual ACC have been reported in patients suffering from depression (2, 3), and the degree of activation in this area correlates with anhedonia, the loss of positive emotions (4). Based on these findings, new approaches for treatmentresistant depression target the subgenual ACC with deep brain stimulation (5). Determining the causal role of subgenual ACC in the regulation of affect and arousal would advance our understanding of emotional regulation and could provide insight into the pathophysiology of depression.A long history of research implicates the ACC as a whole in the control of autonomic arousal, emotional responses, and behavior (6)(7)(8). Much of what is known about the function of the ACC, however, relates to the more dorsal parts of the ACC and its role in higher cognition and arousal (9-11). Less is known about the function of the ventral ACC, especially the subgenual ACC, in part because lesions of the ventromedial prefrontal cortex often include the subgenual ACC as well as adjacent portions of orbitofrontal cortex and the dorsal ACC (12-14). Where research has focused on the primate subgenual ACC, it has emphas...

Childhood maltreatment is a major risk factor for chronic and severe mental and physical health problems across the lifespan. Increasing evidence supports the hypothesis that maltreatment is associated with epigenetic changes that may subsequently serve as mechanisms of disease. The current review uses a systematic approach to identify and summarize the literature related to childhood maltreatment and alterations in DNA methylation in humans. A total of 100 empirical articles were identified in our systematic review of research published prior to or during March 2020, including studies that focused on candidate genes and studies that leveraged epigenome-wide data in both children and adults. Themes arising from the literature, including consistent and inconsistent patterns of results, are presented. Several directions for future research, including important methodological considerations for future study design, are discussed. Taken together, the literature on childhood maltreatment and DNA methylation underscores the complexity of transactions between the environment and biology across development.