The neurochemistry of conduct disorder, antisocial personality disorder, and psychopathy- current evidence and future directions

Increasing evidence from neuroimaging and neurophysiological studies points to structural, functional, and connectivity abnormalities in youths and adults meeting criteria for conduct disorder with and without callous-unemotional traits (CD+/-CU), and antisocial personality disorder with and without psychopathy (ASPD+/-P), respectively. These findings point to neural underpinnings for the core traits and behaviours of these conditions, including aggression and violence, callousness/lack of affective empathy, and maladaptive decision-making. Until recently however, the role of neurochemical systems has been relatively under-researched, with little evidence from well-characterised clinical samples. Over the past decade, new insights have begun to emerge, through more targeted investigations in samples of antisocial populations, particularly in relation to the role of oxytocin, and that of glutamate and GABA in maintaining brain excitatory-inhibitory balance. Alongside this, advances in technology have opened new avenues for probing these mechanisms more precisely. In this paper, we provide an overview of existing evidence, with a focus on recent progress and methodologically robust studies in clinical samples of antisocial populations. We pay particular attention to aggression and violence, given the primacy of these behaviours in CD+/-CU and ASPD+/-P. Within each domain, we propose specific strategies for future research, including novel methodological approaches. We conclude with a suggested set of priorities to help move this field forward towards network and systems understanding of these disorders, and therapeutic interventions. • Over the past decade, new insights have begun to emerge into neurochemistry of Conduct Disorder +/− callous-unemotional traits (CD+/-CU) and Antisocial Personality Disorder +/− Psychopathy, which are reviewed here in the context of previous models and developing technologies • We pay particular attention to the neurochemistry of aggression and violence, but consider also empathy deficits/CU traits and maladaptive decision-making, which have been previously overlooked by reviews • The strongest evidence is for the neurochemistry of aggression, where studies over several decades implicate a prominent role for serotoninergic dysfunction. • More recent work has begun to clarify the putative roles of cortisol, testosterone, and oxytocin in empathy deficits and CU traits, and for dopamine in maladaptive decision-making. • We outline strategies to overcome methodological challenges, and priorities for future work towards translational impact