The mdx mouse model of Duchenne muscular dystrophy (DMD) exhibits pathophysiological responses to graded forms of psychological stress, with phenotypes ranging from transient hypotension and tonic immobility to sustained cardiac instability and lethality. Transgenic dystrophin or utrophin expression in skeletal muscle prevents mdx stress pathology, but the downstream dystrophin-dependent mechanism that mediates mdx stress vulnerability remains to be identified. Metabolic alterations in the kynurenine (KYN) pathway of tryptophan metabolism and the nicotinamide adenine dinucleotide (NAD+) catabolic pathway catalyzed by cluster of differentiation 38 (CD38) are hypothesized to contribute to mdx stress pathology and inter-organ stress response signaling along the skeletal muscle-cardiovascular-central nervous system axis. We demonstrate that KYN and CD38 pathway dysregulation in mdx mice displays stress dependence, but show that genetic modulation of KYN and CD38 pathway activity in mdx mice does not prevent mdx stress pathology. Exploratory multi-omics investigation of protein and metabolic stress signaling factors will provide valuable new insights into the origin of dystrophinopathy-related stress susceptibility, which is translationally relevant to the substantial portion of the DMD community who face chronic life stressors and exhibit pathological responses to psychological stress.