# Exploring dopamine as the master regulator of brain circuitry and mental health genome

**Authors:** Kenneth Blum, Eric R. Braverman, Alireza Sharafshah, Igor Elman, Kai-Uwe Lewandrowski, Abdalla Bowirrat, Albert Pinhasov, Panayotis K. Thanos, Mark S. Gold, Catherine A. Dennen, Edward J. Modestino, Rajendra D. Badgaiyan, David Baron, Brian Fuehrlein, Daniel Sipple, John Wesson Ashford, Keerthy Sunder, Milan Makale, Kevin Murphy, Nicole Jafari, Foojan Zeine, Aryeh R. Pollack, Alexander P.L. Lewandrowski, Jag Khalsa

PMC · DOI: 10.36922/gpd.6557 · Gene & protein in disease · 2025-07-31

## TL;DR

This paper explores how dopamine influences brain circuits and mental health, suggesting it acts as a master regulator.

## Contribution

The paper proposes dopamine as a master regulator of brain circuitry and mental health genome.

## Key findings

- Dopamine's role in addiction is linked to increased transmission.
- Dopamine influences intracellular signaling pathways affecting brain function.
- Dopamine interacts with a network of other neurotransmitters in the brain reward cascade.

## Abstract

Artificially increasing dopamine transmission is the common mechanism by which substances with addictive potential lead to addiction. A key area of research in neurobiology is the role of dopamine. Significant advancements have been made in uncovering the intracellular signaling pathways that mediate both dopamine’s immediate effects and its long-term influence on brain function. Recent discoveries have also highlighted specific molecules that could serve as potential therapeutic targets for neurological and psychiatric disorders. While understanding several important caveats, we believe dopamine acts as a master regulator of brain circuitry across major chromosomes mapping the mental health genome. This view may have important clinical relevance, emphasizing the critical role of dopaminergic activity across the genome. Importantly, we are cognizant that dopamine does not work in insolation, and its finite actions are due to a highly interactive network (known as the brain reward cascade), involving at least seven other major neurotransmitters.

## Full-text entities

- **Genes:** SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, DRD3 (dopamine receptor D3) [NCBI Gene 1814] {aka D3DR, ETM1, FET1}, DBH (dopamine beta-hydroxylase) [NCBI Gene 1621] {aka DBM, ORTHYP1}, ANKK1 (ankyrin repeat and kinase domain containing 1) [NCBI Gene 255239] {aka PKK2, sgK288}, CLOCK (clock circadian regulator) [NCBI Gene 9575] {aka KAT13D, bHLHe8}, DRD2 (dopamine receptor D2) [NCBI Gene 1813] {aka D2DR, D2R}, GNRH1 (gonadotropin releasing hormone 1) [NCBI Gene 2796] {aka GNRH, GRH, LHRH, LNRH}, SLC6A3 (solute carrier family 6 member 3) [NCBI Gene 6531] {aka DAT, DAT1, PKDYS, PKDYS1}, SLC18A1 (solute carrier family 18 member A1) [NCBI Gene 6570] {aka CGAT, VAT1, VMAT1}, DDC (dopa decarboxylase) [NCBI Gene 1644] {aka AADC}, ASPM (assembly factor for spindle microtubules) [NCBI Gene 259266] {aka ASP, Calmbp1, MCPH5}, TH (tyrosine hydroxylase) [NCBI Gene 7054] {aka DYT14, DYT5b, TYH}, DRD4 (dopamine receptor D4) [NCBI Gene 1815] {aka D4DR}, CAMK2G (calcium/calmodulin dependent protein kinase II gamma) [NCBI Gene 818] {aka CAMK, CAMK-II, CAMKG, MRD59}, PPP1R1B (protein phosphatase 1 regulatory inhibitor subunit 1B) [NCBI Gene 84152] {aka DARPP-32, DARPP32}, COMT (catechol-O-methyltransferase) [NCBI Gene 1312] {aka HEL-S-98n}, BMAL1 (basic helix-loop-helix ARNT like 1) [NCBI Gene 406] {aka ARNTL, ARNTL1, BMAL1c, JAP3, MOP3, PASD3}
- **Diseases:** connectivity deficits (MESH:D009461), microcephaly (MESH:D008831), Parkinson's disease (MESH:D010300), bipolar I disorder (MESH:D001714), metabolic diseases (MESH:D008659), amyotrophic lateral sclerosis (MESH:D000690), cancer (MESH:D009369), psychosis (MESH:D011618), insomnia (MESH:D007319), emotional dysregulation (MESH:D021081), binge eating disorder (MESH:D056912), Huntington's disease (MESH:D006816), pain (MESH:D010146), borderline personality disorder (MESH:D001883), mood disorders (MESH:D019964), mental health disorders (OMIM:603663), addictive behaviors (MESH:D000437), schizophrenia (MESH:D012559), anxiety (MESH:D001007), anorexia nervosa (MESH:D000856), depression (MESH:D003866), disordered eating behaviors (MESH:D001068), deficits in multiple cognitive functions (MESH:D003072), intestinal disorders (MESH:D007410), ASD (MESH:D001321), obsessive-compulsive disorder (MESH:D009771), OUD (MESH:D009293), colitis (MESH:D003092), major depressive disorder (MESH:D003865), addiction (MESH:D019966), autism spectrum disorder (MESH:D000067877), irritable bowel disorder (MESH:D043183), ADHD (MESH:D001289), neuropsychiatric disorders (MESH:D001523), gastrointestinal disturbances (MESH:D005767), reward deficiency (MESH:D007153), bulimia nervosa (MESH:D052018)
- **Chemicals:** histamine (MESH:D006632), 3,4-dihydroxyphen ethylamine (MESH:D004298), phenethylamine (MESH:C029261), DOPA (MESH:D004295), L-tyrosine (MESH:D014443), adrenaline (MESH:D004837), Val (MESH:D014633), catecholamine (MESH:D002395), O2 (MESH:D010100), amine (MESH:D000588), GABA (MESH:D005680), tetrahydrobiopterin (MESH:C003402), iron (MESH:D007501), calcium (MESH:D002118), L-3,4-dihydroxyphenylalanine (MESH:D007980), Fe2+ (-), methionine (MESH:D008715), serotonin (MESH:D012701), noradrenaline (MESH:D009638)
- **Species:** Pan troglodytes (chimpanzee, species) [taxon 9598], Homo sapiens (human, species) [taxon 9606]
- **Mutations:** Val158Met, rs3758653, rs1800497

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12311831/full.md

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12311831/full.md

## References

72 references — full list in the complete paper: https://tomesphere.com/paper/PMC12311831/full.md

---
Source: https://tomesphere.com/paper/PMC12311831