Table 2. Causal networks composed of.

upstream molecules known to control the expression of genes showing differential expression in the mPFC and PAG. No statistically significant causal networks were identified for the NAc. Master regulators: predicted upstream molecules at the root of the causal network. Participating regulators: molecules through which a master regulator modulates gene expression in target genes. Data presented have p-value overlap of < 0.05, calculated using Fisher’s exact test.

Brain region	Master Regulator	Molecule Type	Participating regulators	Predicted Activation State	Activation Z- score	Target molecules in dataset
mPFC	melatonin	Endogenous chemical	BAX,CREB1, JUN, melatonin	Activated	2.236	BTG2,CDH1,CYR61,DUSP1, NPAS4
	IFNG	cytokine	CREB1,IFNG, MAPK1,RAC1	Inhibited	−2.121	BATF2,BTG2,CDH1,CYR61 DUSP1,IFI16,NPAS4
	IL15	cytokine	CREB1,IL15, MAPK1, STAT1	Inhibited	−2.449	BATF2,BTG2,CYR61,DUSP1, IFI16,NPAS4
	NTRK1	kinase	CREB1,JUN, NTRK1	Inhibited	−2.236	BTG2,CDH1,CYR61,DUSP1, NPAS4
	K+	endogenous chemical	CREB1,JUN,K+	Inhibited	−2.236	BTG2,CDH1,CYR61,DUSP1, NPAS4
	FGF2	growth factor	CREB1,FGF2, RAC1, STAT1	Inhibited	−2.646	BTG2,CDH1,CYR61,DUSP1, NPAS4
	NTRK2	kinase	CREB1,NTRK2, RAC1,SRC	Inhibited	−2.236	BTG2,CDH1,CYR61,DUSP1, NPAS4
PAG	inosine	endogenous chemical	inosine	Activated	2.449	ARPC1B,C1QA,C1QC, EIF4EBP1,Mt1,TSPO
	CREM	transcription regulator	CREM	Activated	2.236	CSRNP1,IRS2,JUNB, NFKBID,PER1
	PRKCH	kinase	MTOR,PRKCH, STAT3	Activated	2.121	DCTN1,DDAH2,HBA1/HBA2,HES5, HSPB1,MBP,NOTCH1,SOCS3