Table I. Candidate gene findings for the neural circuitry and physiology of acute threat.
| Frontolimbic Neural Circuitrya | Physiologyb | |||||||
|---|---|---|---|---|---|---|---|---|
|
| ||||||||
| Gene | Common Name | Locationc | Published Reports |
Significant Findings |
Null Findings | Published Reports |
Significant Findings |
Null Findings |
| Serotonergic System | ||||||||
| SLC6A4 | Serotonin transporter | 17q11.2 | ||||||
| 5-HTTLPR | Serotonin transporter promoter polymorphismd | 37 | 2217,29,34,35, 37,40,44,49,52,59,65,71 | 1520,49 | 19 | 131,3,6,12,19,22,29,36,37,40,43,69,71 | 620,26,27,35,38,51 | |
| STPP | Serotonin transporter polyadenylation polymorphism | 0 | --- | --- | 1 | 126 | 0 | |
| TPH2 | Tryptophan hydroxylase 2 | 12q21.1 | 4 | 48,10,11,29 | 0 | 1 | 129 | 0 |
| MAOA | Monoamine oxidase A | Xp11.3 | 2 | 245,56 | 0 | 3 | 238,56 | 119 |
| HTR1A | Serotonin receptor 1A | 5p11.2-q13 | 2 | 218,64 | 0 | 1 | 14 | 0 |
| HTR3A | Serotonin receptor 3A | 11q23.1 | 0 | --- | --- | 1 | 121 | 0 |
| Dopaminergic System | ||||||||
| COMT | Catechol-O-methyltransferase | 22q11.21 | 7 | 714,16,32,40,59,60,70 | 0 | 8 | 71,33,40,43,47,50,69 | 151 |
| DAT1 (SLC6A3) | Dopamine transporter | 5p15.3 | 1 | 155 | 0 | 1 | 0 | 151 |
| DRD2 (D2R, D2DR) | Dopamine receptor D2 | 11q23 | 0 | --- | --- | 1 | 130 | 0 |
| DRD4 (D4DR) | Dopamine receptor D4 | 11p15.5 | 0 | --- | --- | 2 | 219,51 | 0 |
| Additional Genes | ||||||||
| ACCN2 (ASIC2) | Amiloride-sensitive cation channel 2 | 12q12 | 1 | 161 | 0 | 0 | --- | --- |
| ADCYAP1R1 | Receptor for adenylate cyclase-activating polypeptide 1 | 7p14 | 1 | 163 | 0 | 2 | 231,57 | 0 |
| ANKK1 (Taq1A)e | Ankyrin repeat and kinase domain containing 1 | 11q23.2 | 0 | --- | --- | 2 | 0 | 230,47 |
| AVPR1a | Arginine vasopressin receptor 1A | 12q14-q15 | 1 | 146 | 0 | 0 | --- | --- |
| BDNF | Brain-derived neurotrophic factor | 11p13 | 4 | 420,39,41,62 | 0 | 8 | 620,21,24,42,48,62 | 241,66 |
| CNR1 (CB1, CNR) | Cannabinoid receptor 1 | 6q14-q15 | 0 | --- | --- | 1 | 128 | 0 |
| CRHR1 | Corticotropin-releasing hormone (CRH) receptor 1 | 17q12-q22 | 0 | --- | --- | 1 | 127 | 0 |
| FAAH | Fatty-acid amide hydrolase | 1p35-p34 | 2 | 223,25 | 0 | 0 | --- | --- |
| GRIN2A | Glutamate receptor, ionotropic, N-Methyl D-Aspartate 2A | 16p13.2 | 1 | 19 | 0 | 1 | 0 | 19 |
| NPSR1 | Neuropeptide S receptor 1 | 7p14.3 | 4 | 413,15,54,68 | 0 | 3 | 215,22 | 154 |
| NPY | Neuropeptide Y | 7p15.1 | 1 | 172 | 0 | 0 | --- | --- |
| NRGN | Neurogranin | 11q24 | 1 | 153 | 0 | 1 | 0 | 153 |
| OPRL1 | Opiate receptor-like 1 | 20q13.33 | 1 | 12 | 0 | 1 | 12 | 0 |
| OXTR | Oxytocin receptor | 3p25 | 1 | 167 | 0 | 1 | 158 | 0 |
| PDYN | Prodynorphin | 20p13 | 1 | 15 | 0 | 1 | 15 | 0 |
| STMN1 | Stathmin 1 | 1p36.11 | 0 | --- | --- | 1 | 17 | 0 |
Note: Superscript numbers refer to the relevant citations in the References list.
a
Includes activation in the amygdala, hippocampus, anterior cingulate cortex, insula, and ventromedial prefrontal cortex.
b
Includes startle, skin conductance, and heart rate outcomes.
c
Location based on Entrez Gene database.
d
Twenty-five of the studies on 5-HTTLPR are reviewed in the Murphy et al.49 meta-analysis.
e
Initially believed to be located in DRD2, the Taq1A restriction fragment length polymorphism has since been located in ANKK1.