Fig. 2: Distinct peak times for rhythmic transcripts in subjects with opioid use disorder (OUD) compared to unaffected comparison (UC) subjects.

A In the dorsolateral prefrontal cortex of UC subjects, transcripts generally peaked at either ZT4 or ZT16, ~12 h apart. Rhythmic transcripts in the DLPFC in subjects with OUD did not peak at consistent times. B In the nucleus accumbens (NAc), rhythmic transcripts in UC subjects generally peaked at ZT10. Rhythmic transcripts in the NAc of subjects with OUD peaked at either ZT11 or ZT23, ~12 h apart. C Transcripts peaking at ZT4 in the DLPFC of UC subjects were enriched for pathways related to rhythms (e.g., circadian rhythm-related genes, sleep) and neurotransmission (e.g., negative regulation of NMDA receptor-mediated neuronal transmission), while transcripts peaking at ZT12 were enriched for immune-related pathways (e.g., adhesion of symbiont to host, negative regulation of innate immune response). Rhythmic transcripts in the DLPFC of OUD subjects were enriched for regulation of neurotrophin TRK receptor signaling pathway and positive regulation of receptor internalization. D Rhythmic transcripts in the NAc of OUD subjects were enriched for apoptotic cleavage of cellular proteins. In the NAc of OUD subjects, rhythmic transcripts peaking at ZT11 were enriched for morphine addiction, glial cell-derived neurotrophic factor receptor signaling, ECM glycoproteins, and synaptic transmission, GABAergic, while transcripts peaking at ZT23 were enriched for opioid signaling, voltage-gated potassium channels, and synapse-related pathways (e.g., regulation of postsynapse organization, chemical synaptic transmission).