Anhedonia, Development, and Emotions: Phenotyping and Therapeutics

a form of transcranial magnetic stimulation, to dorsomedial prefrontal cortex (dmPFC)

Psychosocial add-on intervention that could enhance the effects of TBS. PA Therapy (Craske et al., 2016) is an innovative cognitive and experiential technique developed to address anhedonia specifically and, ideally, change altered patterns of frontostriatal function. Standing in contrast to Cognitive Behavioral Therapy, PA training has efficacy for enhancing positive affect and reducing negative affect (Craske et al., 2018). This treatment can be easily applied, and we propose that it will enhance neural circuit-level changes elicited by TBS.

Ketamine is FDA-approved as an anesthetic agent that will be used off-label in this study. It is used routinely in both pediatric and adult patients and is considered extremely safe in substantially higher, anesthetic doses. The dose to be administered here (0.5 mg/kg) is a much lower, subanesthetic dose, and the administration route (intravenous) is the standard when used in anesthesia. Published studies and metaanalyses of this dose of intravenous ketamine as an off label use in depression show clearly that there are no increased risks in this population, including a recent study in adolescents (Dwyer et al, 2021, American Journal of Psychiatry). A single dose of ketamine will be used to determine if it alters the functioning of the anhedonia-related reward functioning and frontostriatal biomarkers assessed in this study.