Figure 1
The metabolic pathway converting serotonin to melatonin involves the enzymes AANAT and ASMT (previously known as HIOMT). Although AANAT has been believed to control the rate-limiting step, recent studies [13] imply an effect of ASMT upon the metabolic conversion of serotonin to melatonin. The activity of both AANAT and ASMT might influence the concentration of N-acetylserotonin, which influences expression of TRKB (a BDNF receptor).
Table 1
Studies Included
| Study | Participants | N | % Male | Median age (range) | Diagnoses |
|---|---|---|---|---|---|
| Delayed sleep phase disorder | Cases and Controls | 768 | 33% | 35 (22-82) | DSPD or no DSPD |
| Sleep Clinic | Scripps sleep disorders patients | 853 | 65% | 57 (21-96) | Sleep apnea, DSPD, insomnia, etc. |
| MrOS | Volunteers, multi-center | 2540 | 100% | 76 (67-96) | Mixed diagnoses or none |
| SOF | Volunteers, multi-center | 1731 | 0% | 83 (79-99) | Mixed diagnoses or none |
| Bipolar disorder | VA clinic patients | 80 | 63% | 46 (21-67) | All had bipolar disorder |
Table 2
Association of ASMT rs4446909 with depression scales.
| Study | rs4446909 P | rs4446909 R2 | rs4446909 Beta |
|---|---|---|---|
| DSPD | 0.01 | 0.007 | -0.74 |
| Sleep Clinic | 0.10 | 0.004 | 0.40 |
| MrOS | 0.06 | 0.0003 | 0.02* |
| SOF | 0.26 | .0006 | 0.01* |
P: nominal values, corrected for genomic inflation, are for additive association of the minor allele of rs4446909 with the QIDS or GDS depression self-rating. Recessive models were not more significant.
R2: squared correlation representing percent variance explained by the association of the depression score and rs4446909, uncorrected for covariates.
Beta: for DSPD, a negative beta indicated that as the A allele decreases in amount (frequency), and G alleles increase, QIDS depression scores increase. The not-significant Beta's for the Sleep Clinic, MrOS, and SOF participants were in the opposite direction from the DSPD sample.
* Beta for the log transform of GDS+1 suggested a 2% increase in GDS score over the range of 1 to 16 per A allele.