In Part 1 of this article, published in Current Psychiatry January 2020,1 I discussed how medical knowledge is growing faster than ever, and the challenge to keep up with the ever-growing body of information is greater than ever. I described a 3-step methodology I used to sort and evaluate published research that was ready for clinical application. This led me to select 12 top articles published between July 1, 2018 and June 30, 2019, chosen based on their clinical relevance/applicability. In Part 1 I discussed 6 of these 12 studies. In Part 2, I present brief descriptions of the remaining 6 papers chosen by this methodology. These studies are summarized in the Table.2-7 The order in which they appear in this article is arbitrary.
1. Han LKM, Aghajani M, Clark SL, et al. Epigenetic aging in major depressive disorder. Am J Psychiatry. 2018;175(8):774-782.
In light of the association of major depressive disorder (MDD) with an increased risk of aging-related diseases, Han et al2 examined whether MDD was associated with higher epigenetic aging in blood as measured by DNA methylation patterns. They also studied whether clinical characteristics of MDD had a further impact on these patterns, and whether the findings replicated in brain tissue. Many differentially methylated regions of our DNA tend to change as we age. Han et al2 used these age-sensitive differentially methylated regions to estimate chronological age, using DNA extracted from various tissues, including blood and brain.
Study design
- As a part of the Netherlands Study of Depression and Anxiety (NESDA), this study included 811 patients with MDD and 319 control participants with no lifetime psychiatric disorders and low depressive symptoms (Inventory of Depressive Symptomatology score <14).
- Diagnosis of MDD and clinical characteristics were assessed by questionnaires and psychiatric interviews. Childhood trauma was assessed using the NEMESIS childhood trauma interview, which included a structured inventory of trauma exposure during childhood.
- DNA methylation age was estimated using all methylation sites in the blood of 811 patients with MDD and 319 control participants. The residuals of the DNA methylation age estimates regressed on chronological age were calculated to indicate epigenetic aging.
- Analyses were adjusted for sociodemographic characteristics, lifestyle, and health status.
- Postmortem brain samples of 74 patients with MDD and 64 control participants were used for replication.
Outcomes
- Significantly higher epigenetic aging was observed in patients with MDD compared with control participants (Cohen’s d = 0.18), which suggests that patients with MDD are biologically older than their corresponding chronological age. There was a significant dose effect with increasing symptom severity in the overall sample.
- In the MDD group, epigenetic aging was positively and significantly associated with childhood trauma.
- The case-control difference was replicated in an independent analysis of postmortem brain samples.
Conclusion
- These findings suggest that patients with MDD and people with a history of childhood trauma may biologically age relatively faster than those without MDD or childhood trauma. These findings may represent a biomarker of aging and might help identify patients who may benefit from early and intensive interventions to reduce the physical comorbidities of MDD.
- This study raises the possibility that MDD may be causally related to epigenetic age acceleration. However, it only points out the associations; there are other possible explanations for this correlation, including the possibility that a shared risk factor accounts for the observed association.
2. Wu YC, Tseng PT, Tu YK, et al. Association of delirium response and safety of pharmacological interventions for the management and prevention of delirium: a network meta-analysis. JAMA Psychiatry. 2019;76(5):526-535.
Delirium is common and often goes underdiagnosed. It is particularly prevalent among hospitalized geriatric patients. Several medications have been suggested to have a role in treating or preventing delirium. However, it remains uncertain which medications provide the best response rate, the lowest rate of delirium occurrence, and the best tolerability. In an attempt to find answers to these questions, Wu et al3 reviewed studies that evaluated the use of various medications used for delirium.
Study design
- Researchers conducted a systematic review and network meta-analysis of randomized controlled trials (RCTs) that investigated various pharmacologic agents used to treat or prevent delirium.
- Fifty-eight RCTs were included in the analyses. Of these, 20 RCTs with a total of 1,435 participants compared the outcomes of treatments of delirium, and 38 RCTs with a total of 8,168 participants examined prevention.
- A network meta-analysis was performed to determine if an agent or combinations of agents were superior to placebo or widely used medications.
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