Stimulated by Liao et al 2023.[1]
LGTD – longitudinal generation tracking database
key to acronyms
NHIRD – national health insurance research database (Taiwan)
aHR – adjusted hazard ratio
IL6 – interleukin 6
IL1β – interleukin 1β
TNF – tumour necrosis factor
ALB – albumin
VEGFA – vascular endothelial growth factor A
CRP – C-reactive protein
PTGS2 – prostaglandin-endoperoxide synthetase 2 (aka cyclooxygenase)
BDNF – brain-derived neurotropic factor
I guess what caught my eye in the title of this paper was the 19-year follow-up. It is another retrospective observational cohort study from Taiwan, but this time using the LGTD – a subset of the NHIRD. The LGTD 2000 comprises claims data from a random sample of 2 million patients from the NHIRD spanning the period from 2000 to 2018.
The authors searched for female patients from 13 to 50 years of age with a new diagnosis of dysmenorrhoea and at least 2 outpatient or inpatient claims for the condition between the start of 2000 and the end of 2017. The primary outcome was the incidence of depression in the follow-up period, which could be as long as 19 years. The incidence of depression is increased in patients with dysmenorrhoea and one review estimates the relative risk as 1.72.[2]
The authors tell us that a complete course of acupuncture treatment in Taiwan is considered to be 6 consecutive treatments, so the acupuncture cohort was defined by having at least 6 sessions after the diagnosis and the non-acupuncture cohort was defined by having no acupuncture. This resulted in 87k who had acupuncture and 100k who did not.
Individuals with a variety of gynaecological comorbidities or a prior history of depression were excluded, leaving around 55k in each cohort. Propensity score matching using the usual baseline comorbidities and relevant medications (oral contraceptives and NSAIDs) reduced the cohorts further to around 35k each.
After matching there were still significant differences between the cohorts, with the acupuncture cohort having slightly more individuals with migraine and substantially more with insomnia. Both conditions probably increase the risk of depression, so these imbalances in the cohort do not favour acupuncture, indeed, the risk of developing depression is likely to be more than doubled in individuals with insomnia.[3]
The interaction with migraine is not so clear. A recent Mendelian randomisation study confirms a causal link between major depression and increased risk of migraine, but not the reverse, at least in terms of the genetic markers of disease.[4]
The main result of this paper demonstrates a risk reduction associated with acupuncture of 64% (aHR 0.36). As we have seen before in these studies, this risk reduction seems to exceed the increased risk from the condition itself, suggesting that acupuncture might reduce your risk of depression even if you did not have dysmenorrhoea.
There was also a signal suggesting a dose response, with more acupuncture sessions being associated with a lower risk of depression. The confidence intervals were wide, so this is cannot be considered a definitive finding.
The authors also investigated possible mechanisms underlying their findings using a bioinformatics analysis of gene function. This is like a separate study in its own right and produced some fancy figures for their paper, although much of the analysis is beyond my abilities to criticise in any way. I will just have to take their word for it when they implicate the genes coding for following as being potentially involved in the interactions of acupuncture, dysmenorrhoea, and depression: IL6; IL1β; TNF; ALB; VEGFA; CRP; PTGS2; and BDNF.
References
1 Liao C-C, Lin C-L, Tsai F-J, et al. Acupuncture’s long-term impact on depression prevention in primary dysmenorrhea: A 19-year follow-up of a Taiwan cohort with neuroimmune insights. J Affect Disord. 2023;S0165-0327(23)01194-1.
2 Zhao S, Wu W, Kang R, et al. Significant Increase in Depression in Women With Primary Dysmenorrhea: A Systematic Review and Cumulative Analysis. Front Psychiatry. 2021;12:686514.
3 Li L, Wu C, Gan Y, et al. Insomnia and the risk of depression: a meta-analysis of prospective cohort studies. BMC Psychiatry. 2016;16:375.
4 Lv X, Xu B, Tang X, et al. The relationship between major depression and migraine: A bidirectional two-sample Mendelian randomization study. Front Neurol. 2023;14:1143060.
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