Genes, Stress, and Depression: Is There an Interaction?
What's Hot in Medicine; March/April 2011
by David W. Sharp
We have to dig deep in the citation rankings this time to uncover a novel topic, but before doing that an influenza update may be in order. Here in the U.K. influenza was in retreat by the end of January and the dominant virus was becoming B rather than the pandemic A H1N1 . Non-selective vaccination coverage has been targeted at the over-65s, but in future more thought may have to be given to children.
A survey of 70 deaths in the 0-18 years age group in a nine-month period in 2009-10 in England revealed that 21% of these children did not have a severe underlying illness (N. Sachedina, L.J. Donaldson, Lancet,376[9755]: 1846-52, 2010). These deaths outnumbered the toll of leukemia, and no single infectious disease had caused as many fatalities since meningococcal meningitis in 2001.
H1N1 influenza has been a hot topic for the mass media and the academic and professional press for almost two years now, with more than 2,300 pertinent papers indexed in the Thomson Reuters Web of Science® since the beginning of 2010. And for Science Watch, too: 7 of the top 25 papers in medicine this time are on pandemic H1N1 influenza.
Colorized negative stained transmission electron
micrograph (TEM) depicted some of the ultrastructural morphology of the
A/CA/4/09 swine flu virus.
One newcomer makes the current Top Ten. Reporting from Canada, Dr. Anand Kumar and colleagues (#10) describe details of 168 patients with confirmed or probable influenza A (H1N1) infection who were admitted to participating intensive-care units in a three-month period in 2009. Importantly, the mean age was only 32 years; 50 patients were children and 4 of those died.
The emergence of pandemic H1N1 indicates an important antigenic shift. All the same, might there be some pre-existing immunity? Dr. Kathy Hancock and her colleagues from the U.S. Centers for Disease Control and Prevention report that cross-reactive antibody responses to the pandemic virus are far more likely to be found in those born before 1950 than in the under-18s (K. Hancock, et al., New Engl. J. Med.,361[20]: 1945-52, 2009; currently at #24, with 30 citations in the current period and 123 overall).
Eight years ago Science published a paper indicating that the influence of stress in depression might by affected by variation (short or long alleles) in the promoter region of the serotonin transporter gene 5-HTPLPR. The Science paper, indicating a gene-environment interaction, was clearly important, and several groups have tried to replicate it.
In a meta-analysis of data available through March, 2009, Dr. Neil Risch and his colleagues (#17; JAMA,301[23]: 2462-71, 2009; total cites 154, latest count 35) identified 14 studies that met their criteria. These exercises are essentially statistical, but, in a way, a table summarizing the 13 attempts at replication says it all.
All five studies with more than 1,000 participants failed to replicate the finding; two others also failed, with findings in the opposite direction; there was partial replication in three; and replication in only three. Statistical analysis confirmed the absence of a significant interaction between genotype, stressful life events, and depression.
"Statistical analysis confirmed the absence of a significant interaction between genotype, stressful life events, and depression."
Two years have passed since Risch and colleagues’ data-collection point. Other investigations have appeared, including twin studies from the Netherlands and Australia, both non-replicative. Some commentators have noted that the way stress is measured may be important here. For example, there appear to be more replications when interviewing or more objective measures are used. Also, other lines of evidence should be considered, and one recent review concludes that "a broader approach based on evidence from different research fields and methodologies supports a 5-HTTLPR by stress interaction" (I.M. Wankerl, S. Wust S, C. Otte, Curr. Opin. Psychiatry,23[6]: 582-7, 2010).
What goes into a meta-analysis and what is excluded is vital. The deadline
in the study we have been examining (#17) is only eight months earlier than
that for another meta-analysis that appeared as this column was being
drafted (K. Karg, et al., Arch. Gen. Psychiatry,Epub, 3
January 2011), but the later one has 54 studies in it compared with 14.
This indicates, not a flurry of publishing activity in mid-2009, but a
different approach to study selection. The conclusion this time is that
there is "strong evidence" of an interaction between stress of all sorts,
depression and 5-HTTLPR. On we go.
A former deputy editor of The
Lancet, David W. Sharp, M.A. (Cambridge), is a
freelance writer living in Minchinhampton, Gloucestershire,
U.K.
What's Hot in Medicine | |||
---|---|---|---|
Rank | Paper |
Cites This Period Sep-Oct 10 |
Rank Last Period Jul-Aug 10 |
1 | Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team (F.S. Dawood, et al.), "Emergence of a novel swine-origin influenza A (H1N1) virus in humans," New Engl. J. Med., 360(25): 2605-15, 18 June 2009. [Writing group: Ctrs. for Disease Control & Prevent., Atlanta, GA] *458WR | 71 | 1 |
2 | F.H. Schröder, et al., "Screening and prostate-cancer mortality in a randomized European study," New Engl. J. Med., 360(13): 1320-8, 26 March 2009. [15 institutions worldwide] *423VP | 59 | 2 |
3 | P.C. Fong, et al., "Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers," New Engl. J. Med., 361(2): 123-34, 9 July 2009. [7 U.K.. and European institutions] *467OS | 57 | 6 |
4 | NICE-SUGAR Study Investigators (S. Finfer, et al.), "Intensive versus conventional glucose control in critically ill patients," New Engl. J. Med., 360(13): 1283-97, 26 March 2009. [Writing Committee: 4 Australian, New Zealand, and Canadian institutions] *423VP | 55 | † |
5 | W. Duckworth, et al., "Glucose control and vascular complications in veterans with type 2 diabetes," New Engl. J. Med., 360(2): 129-39, 8 January 2009. [11 U.S. institutions] *391UG | 45 | † |
6 | T.S. Mok, et al., "Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma," New Engl. J. Med., 361(10): 947-57, 3 September 2009. [14 institutions worldwide] *490EI | 45 | 3 |
7 | S.J. Connolly, et al., "Dabigatran versus warfarin in patients with atrial fibrillation," New Engl. J. Med., 361(2): 1139-51, 17 September 2009. [12 institutions worldwide] *494QA | 43 | 10 |
8 | A.S. Levey, et al., "A new equation to estimate glomerular filtration rate," Ann. Internal Med.,150(9): 604-12, 5 May 2009. [6 U.S. institutions] *443IQ | 43 | † |
9 | D.L. Ge, et al., "Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance," Nature, 461(7262): 399-401, 17 September 2009. [Duke U., Durham, NC; Schering-Plough Res. Inst., Kenilworth, NJ; Johns Hopkins U., Baltimore, MD] *494QB | 42 | † |
10 | A. Kumar, et al., "Critically ill patients with 2009 influenza A(H1N1) infection in Canada," JAMA, 302(17): 1872-9, 4 November 2009. [24 Canadian institutions] *514DU | 41 | † |
SOURCE: Thomson Reuters Hot Papers Database. Read the Legend. |
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