The Editor’s choice October 2021
written by Jess G. Fiedorowicz, Editor-in-Chief, Journal of Psychosomatic Research, Professor and Senior Research Chair in Adult Psychiatry, University of Ottawa, Head and Chief of Mental Health, The Ottawa Hospital Scientist, Ottawa Hospital Research Institute, October 2021
The Editor’s Choice –
This quarter’s Editor’s Choice selection was selected from eight articles that had editorial manuscript ratings high enough to contend. This chosen article was selected to for both ease of discussion, given my own prior work in this area, as well as to send an editorial message about the potential merit of negative studies and the value in not spinning these into some positive post hoc result. We are quite wary of papers that appear as if they may be presenting some exploratory analysis as if it was hypothesis testing with some a priori statistical analysis plan or spinning some secondary finding into a primary result of focal point of the paper. We have no reservations about publishing negative studies and great discomfort at the idea of perpetuating what any Type I error that may result from these too common breeches of scientific integrity. Negative studies are important in the scientific literature and crucial to advancing the field. In the case of the current selection, the results bring additional clarity to the relationship between depressive symptoms and disorders and risk of cardiovascular disease.
Our Editor’s Choice entitled “Childhood-onset depression and arterial stiffness in young adulthood” by Emma Barinas-Mitchell and colleagues appears in the current October issue of the Journal of Psychosomatic Research (1). The study utilizes a prospective cohort of probands and siblings recruited between 1997 and 2006 from 23 child mental health facilities in Hungary. These individuals underwent extensive risk assessments for cardiovascular disease, including an assessment of carotid-femoral pulse wave velocity (PWV) between 2016 and 2019 at which time participants were a mean of 25 years old and an average of 15 years after their initial assessment for major depressive disorder. A total of 732 individuals underwent assessment of PWV: 294 probands, 269 unaffected siblings, and another 169 controls. PWV did not differ by group in either unadjusted or adjusted analyses. It was also not related to age of onset, number of episodes or percent of life depressed. The study did however find that those with childhood-onset depression had less physical activity, greater smoking, and a higher risk of obesity, even adjusting for parental history. The authors concluded any effects of depression on cardiovascular risk may be mediated by these behavioral and related risk factors in early adulthood and that any impact on arterial stiffness or other cardiovascular outcomes may occur later in life.
The results and conclusions drawn by Barinas-Mitchell et al. mirror that of some of my teams work on cardiovascular risk in bipolar disorder, which shows that vascular dysfunction and cardiovascular risk appears to develop over the long-term course of illness and in a dose-response to symptom burden (2). Nine years ago, we published a paper in the journal looking at PWV in bipolar disorder. In the portion of our sample below age 32 (median split) PWV values were consistent with age-based population norms, but in the older half of the sample, PWV deviated from these age-based norms and in proportion with burden of illness (3). With the entire sample age 32 or younger, the findings of Barinas-Mitchell et al. are consistent with this and other studies.
Negative studies like the featured article by Barinas-Mitchell et al. can provide valuable information and save the scientific community tremendous expense. We recently failed to take lessons learned from negative results into the design of a clinical trial. While we had previously shown an association between anxiety and vascular dysfunction in an older adult sample only amongst those with existing atherosclerotic vascular disease (4), we nonetheless embarked on a clinical trial of acceptance and commitment therapy for anxiety and secondarily looked at vascular outcomes in a young sample without cardiovascular disease. We have recently published the results of this trial, which showed improvements in anxiety, but not vascular function (5). The inclusion and exclusion criteria ideally should have selected for those with vascular disease or dysfunction. This design oversight further occurred despite both the associations with anxiety by Stillman et al. (4) and the potentially relevant findings mentioned above for bipolar disorder. Studies of interventions, proposed mediators, or surrogate outcomes need to appreciate timeline and pathways by which a given exposure may influence outcome. Studies such as our Editor’s Choice by Barinas-Mitchell and colleagues can provide important information for future studies, so long as any conclusions drawn from the results are appropriately heeded.
- Barinas-Mitchell E, Yang X, Matthews KA, Columbus ML, George CJ, Dosa E, et al. Childhood-onset depression and arterial stiffness in young adulthood. J Psychosom Res. 2021;148:110551.
- Fiedorowicz JG. Depression and cardiovascular disease: an update on how course of illness may influence risk. Curr Psychiatry Rep. 2014;16(10):492.
- Sodhi SK, Linder J, Chenard CA, Miller del D, Haynes WG, Fiedorowicz JG. Evidence for accelerated vascular aging in bipolar disorder. J Psychosom Res. 2012;73(3):175-9.
- Stillman AN, Moser DJ, Fiedorowicz J, Robinson HM, Haynes WG. Association of anxiety with resistance vessel dysfunction in human atherosclerosis. Psychosom Med. 2013;75(6):537-44.
- Fiedorowicz JG, Dindo L, Ajibewa T, Persons J, Marchman J, Holwerda SW, et al. One-day acceptance and commitment therapy (ACT) workshop improves anxiety but not vascular function or inflammation in adults with moderate to high anxiety levels in a randomized controlled trial. Gen Hosp Psychiatry. 2021;73:64-70.