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Serotonin transporter polymorphism, memory and hippocampal volume in the elderly: association and interaction with cortisol
O'Hara R, Schröder CM, Mahadevan R, Schatzberg AF, Lindley S, Fox S, Weiner M, Kraemer HC et al.. Molecular psychiatry, 2007-03-13
Topic: Brain proteins, microglia and lab models
The s allele variant of the serotonin transporter gene (5-HTT) has recently been observed to moderate the relationship of stress to depression and anxiety. To date no study has considered interactive effects of 5-HTT genotype, stress and hypothalamic-pituitary-adrenal (HPA) function on cognition in healthy, older adults, which may reflect developmental, functional or neurodegenerative effects of the serotonin transporter polymorphism. We investigated whether 5-HTT genotype interacts with cumulative life stress and HPA-axis measures of waking and diurnal cortisol slope to impact cognition in 154 non-depressed, older adults. Structural images of hippocampal volume were acquired on a subsample of 56 participants. The 5-HTT s allele was associated with both significantly lower delayed recall and higher waking cortisol levels. Presence of the s allele interacted with higher waking cortisol to negatively impact memory. We also observed a significant interaction of higher waking cortisol and the s allele on lower hippocampal volume. Smaller hippocampi and higher cortisol were associated with lower delayed recall only in s allele carriers. No impact or interactions of cumulative life stress with 5-HTT or cortisol were observed. This is the first investigation to identify an association of the 5-HTT s allele with poorer memory function in older adults. The interactive effects of the s allele and waking cortisol levels on reduced hippocampal volume and lower memory suggest that the negative effect of the serotonin polymorphism on memory is mediated by the HPA axis. Further, given the significant association of the s allele with higher waking cortisol in our investigation, future studies may be needed to evaluate the impact of the serotonin transporter polymorphism on any neuropsychiatric or behavioral outcome which is influenced by HPA axis function in older adults.
Key findings
- The 5-HTT s allele was associated with both significantly lower delayed recall and higher waking cortisol levels.
- We also observed a significant interaction of higher waking cortisol and the s allele on lower hippocampal volume.
- Smaller hippocampi and higher cortisol were associated with lower delayed recall only in s allele carriers.
- The interactive effects of the s allele and waking cortisol levels on reduced hippocampal volume and lower memory suggest that the negative effect of the serotonin polymorphism on memory is mediated by the HPA axis.
- Further, given the significant association of the s allele with higher waking cortisol in our investigation, future studies may be needed to evaluate the impact of the serotonin transporter polymorphism on any neuropsychiatric or behavioral outcome which is influenced by HPA axis function in older adults.
Study details
- Participants56
- Evidence strengthLow
How this study scored 47/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 27 of the 58 points we could judge it on, which is 47 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Molecular psychiatry) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2007 — within 20 year(s) of the newest study here |
| Sample size | 1 / 4 | 56 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 17353910) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 27 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 27 of the 58 points we could judge it on is 47 out of 100. |
| Total | 47 / 100 | — |
What each of these 20 components measures, and what this score is not →
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APA 7th
O'Hara, R., Schröder, C. M., Mahadevan, R., Schatzberg, A. F., Lindley, S., Fox, S., et al. (2007). Serotonin transporter polymorphism, memory and hippocampal volume in the elderly: association and interaction with cortisol. Molecular psychiatry. https://doi.org/10.1038/sj.mp.4001978
Vancouver
O'Hara R, Schröder CM, Mahadevan R, Schatzberg AF, Lindley S, Fox S, et al. Serotonin transporter polymorphism, memory and hippocampal volume in the elderly: association and interaction with cortisol. Molecular psychiatry. 2007. doi:10.1038/sj.mp.4001978. PMID: 17353910.
BibTeX
@article{ohara2007-17353910,
author = {O'Hara, R. and Schröder, C. M. and Mahadevan, R. and Schatzberg, A. F. and Lindley, S. and Fox, S. and Weiner, M. and Kraemer, H. C. and others},
title = {{Serotonin transporter polymorphism, memory and hippocampal volume in the elderly: association and interaction with cortisol}},
journal = {Molecular psychiatry},
year = {2007},
doi = {10.1038/sj.mp.4001978},
pmid = {17353910},
url = {https://doi.org/10.1038/sj.mp.4001978}
}