Transcriptomic Dysregulation in Animal Models of Attention-Deficit Hyperactivity Disorder and Nicotine Dependence Suggests Shared Neural Mechanisms.

INTRODUCTION

Attention-deficit-hyperactivity disorder (ADHD) is highly heritable and increases the likelihood of nicotine dependence (ND). The self-medication hypothesis of nicotine use in ADHD proposes that ADHD patients seek nicotine for its ability to improve their symptoms, and they have less success quitting, possibly due to the worsening of ADHD symptoms in withdrawal.

METHODS

The present analysis compared transcriptomic data from the brains of rodent models of ADHD and those of ND, with a focus on striatal gene expression. Differential expression analysis, pathway enrichment analysis, and gene-network mapping identified signaling networks and candidate genes that may contribute to the high co-occurrence between ADHD and ND.

RESULTS

We identified novel differentially expressed genes (PRKAG2, MAPK1), and genes with known associations to either ADHD or ND (ANK3, CALD1, CHRNA4, CHRNA7, CMTM8, DLG4, DUSP6, GNG3, GNG11, GRIK5, GRINA2, GRM5, ICAM2, KCNJ6, PRKAB1, SNAP25, SYNPO, SYT1, VAMP2). In addition, synaptic transmission (hsa04728, R-HAS-112315, R-HSA-442755) and MAPK signaling pathways (hsa04010, hsa04014, hsa04015, R-HSA-5673001, R-HSA-5684996) were enriched in both ADHD and ND.

CONCLUSION

The signaling pathways implicated by this analysis mediate neurological mechanisms known to contribute to ND. The association of analogous differently expressed genes and common signaling pathways suggests an important causal relationship between ND and ADHD that may be clinically important.