The Lancet: Subverting Perception! The largest meta-analysis to date suggests that adults with major depressive disorder with childhood trauma benefit from aggressive treatment

*For medical professionals only

Childhood trauma, manifested as emotional or physical neglect up to age 18, or emotional, physical, or sexual abuse, is a common and major risk factor for the development and worsening of depressive disorder in adulthood [1].

Patients with depressive disorder with a history of childhood trauma typically have early onset, high recurrence rates, many comorbidities, and poor response to psychotherapy or pharmacotherapy [2], but childhood trauma is as high as approximately 46 percent in adults with depressive disorder and even higher in patients with chronic depressive disorder [3].

Previous studies have shown that a history of childhood trauma is associated with poor response to first-line treatment of depressive disorder [1].

This means that new personalized treatment for patients with major depressive disorder and a history of childhood trauma is urgent
.
However, the evidence for poor treatment outcomes in these populations is not clear and sufficient [4], and the conclusions of studies are inconsistent [5].

So, what is the impact of childhood trauma history on the efficacy and effectiveness of first-line treatment in adult patients with major depressive disorder? Do adults with major depressive disorder with a history of childhood trauma benefit from aggressive treatment? Also, Does the type of childhood trauma have an effect?

Recently, the research team of the meta-analysis of childhood trauma published important research results
in The Lancet Psychiatry.
This meta-analysis, the largest and most comprehensive study of the available evidence, showed that although patients with major depressive disorder with childhood trauma had more severe depressive symptoms before and after treatment, this population had similar benefits from acute treatment as patients with major depressive disorder without childhood trauma and showed similar dropout rates; In addition, different types of childhood trauma and treatment options, i.
e.
, psychotherapy or medication, presented consistent conclusions
in terms of findings.

Screenshot of the cover of the paper

Let's take a look at how this study is carried out
.

This review selected three literature databases, including PubMed, PsycINFO and Embase, to search the literature between 21 November 2013 and 16 March 2020 to determine English-language journal literature on the effects of childhood trauma and adult depressive disorder; In addition, full-text screening was performed from three source pools of randomized controlled trials (RCTs) [6-8], including randomized controlled trials and open trials, comparing the efficacy or effectiveness
of evidence-based medical treatments, psychotherapies, or co-interventions in adults with depressive disorders and childhood traumatic experiences.

The primary outcome of the study was change in depression severity from baseline to the end of the acute treatment period, expressed as standardised effect size (Hedges'g), and meta-analysed using a random-effects
model.

ADtaxi Memories Trip Vol.
05 Listen to Professor Henrik Zettberg of the Institute of Neuroscience and Physiology, University of Gothenburg, Sweden, to take you through the future of AD biomarkers

Twenty RCTs and nine open-label trials were included in the final meta-analysis, with 59% of the studies focusing on people with major depressive disorder and 38% on people
with chronic or treatment-resistant depressive disorder.

The study involved a total of 6830 participants, 62% of whom reported experiencing childhood trauma
.
The most common types of childhood trauma were emotional neglect (2198/3799, 58%) and emotional abuse (2494/4785, 52%), followed by physical abuse (1709/4023, 42%), physical neglect (1196/3024, 40%) and sexual abuse (1328/3815, 35%)
.
Of the 57 trial groups, 47% received psychotherapy, 37% received medication, 2% received combination therapy, and 14% were controls
.

The results showed a significant increase in depression severity at baseline in adults with childhood traumatic experience compared with adults with depressive disorder who did not experience trauma in childhood (g=0.
202, 95% CI: 0.
145 to 0.
258; P＜0.
001）
。 Symptom improvement was more pronounced in children with childhood trauma who received active treatment than in the control group who did not receive active treatment (g=0.
605, 95% CI: 0.
294 to 0.
916; P=0.
0015）
。 In addition, there was no significant difference in dropout rates among adults with depressive disorder with or without childhood traumatic experiences (RR = 1.
063, 95% CI = 0.
945 to 1.
195; P=0.
30）
。

Results of the meta-analysis (note: Egger's test was used to assess publication bias; † is the effect after shearing (if significant heterogeneity is observed, outliers are excluded); ‡Childhood trauma / No childhood trauma; § Baseline/post-treatment; ¶ Treatment group/control group; || withdrawal from the childhood trauma group/withdrawal from the no childhood trauma group; **RR（95% CI）； †† for corrected RR)

In addition, there was no significant difference in the improvement of depressive symptoms between adult depressive disorder patients with and without childhood trauma from baseline to acute treatment (g=0.
016, 95% CI: -0.
094-0.
125; P = 0.
77), that is, adult patients with depressive disorder with childhood traumatic experiences had more severe depressive symptoms before and after treatment, but compared with patients without a history of childhood trauma, they had significant and similar treatment effects, including psychotherapy and pharmacotherapy
.
There were also no significant differences
in the different types of childhood trauma.

Standardized (weighted) mean of depression severity at baseline and after treatment in patients with or without a history of childhood trauma

The study is bright in many ways, but it still has certain limitations
.

First, the statistical heterogeneity of the study was moderate to high, suggesting that there were other potential influencing factors
in the study in addition to those tested in this meta-analysis.
Second, due to methodological limitations and access to data [9], the study did not test for sex specificity or control for potential confounders, so meta-analysis of individual case data is necessary
.

In addition, because not all study authors were able to provide their raw data, this could lead to an increased likelihood of bias, and specific subgroups, such as trauma-focused therapy versus other psychological therapies or combination therapy versus monotherapy
, could not be examined in this study.
In addition, this meta-analysis focused on symptom improvement during acute treatment, but adult patients with depressive disorder with childhood traumatic experiences tend to have residual symptoms after treatment and a higher risk of recurrence, so they may benefit much
less from treatment in the long term than those without childhood trauma.

Finally, childhood trauma was retrospective in all included studies, considering differences in consistency between prospective and retrospective studies [10], and the generality of this study was limited to retrospective childhood trauma
.

Overall, the meta-analysis concluded that patients with a history of childhood trauma showed more severe depressive symptoms at baseline, highlighting the importance of
relevant history assessment early in treatment.
In addition, this meta-analysis concludes contrary to previous meta-analyses that depressive symptoms in adults with a history of childhood trauma improve significantly with
medication and psychotherapy.

Therefore, regardless of whether there is a history of childhood trauma, patients with major depressive disorder should receive medication and psychotherapy based on evidence-based medical evidence, and this conclusion also gives a reassurance to the clinical treatment of depressive disorder
.
In addition, it is recommended that childhood trauma as a risk factor
be addressed early in the treatment of depressive disorders.

References:

[1] Nelson J, Klumparendt A, Doebler P, Ehring T.
Childhood maltreatment and characteristics of adult depression: meta-analysis.
Br J Psychiatry 2017; 210: 96–104.

[2] Hovens JG, Wiersma JE, Giltay EJ, et al.
Childhood life events and childhood trauma in adult patients with depressive, anxiety and comorbid disorders vs.
controls.
Acta Psychiatr Scand 2010; 122: 66–74.

[3] Struck N, Krug A, Yuksel D, et al.
Childhood maltreatment and adult mental disorders: the prevalence of different types of maltreatment and associations with age of onset and severity of symptoms.
Psychiatry Res 2020; 293: 113398.

[4] Nanni V, Uher R, Danese A.
Childhood maltreatment predicts unfavorable course of illness and treatment outcome in depression: a meta-analysis.
Am J Psychiatry 2012; 169: 141–51.

[5] Heinonen E, Knekt P, Harkanen T, Virtala E, Lindfors O.
Childhood adversities as predictors of improvement in psychiatric symptoms and global functioning in solution-focused and short- and longterm psychodynamic psychotherapy during a 5-year follow-up.
J Affect Disord 2018; 235: 525–34.

[6] Cuijpers P, Karyotaki E, Ciharova M, et al.
A meta-analytic database of randomised trials on psychotherapies for depression.
2020.
https://osf.
io/825c6/ (accessed on Jan 27, 2020).

[7] Cipriani A, Furukawa TA, Salanti G, et al.
Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis.
Lancet 2018; 391: 1357–66.

[8] Vinkers CH, Lamberink HJ, Tijdink JK, et al.
The methodological quality of 176,620 randomized controlled trials published between 1966 and 2018 reveals a positive trend but also an urgent need for improvement.
PLoS Biol 2021; 19: e3001162.

[9] Cuijpers P, Griffin JW, Furukawa TA.
The lack of statistical power of subgroup analyses in meta-analyses: a cautionary note.
Epidemiol Psychiatr Sci 2021; 30: e78.

[10] Danese A, Widom CS.
Objective and subjective experiences of child maltreatment and their relationships with psychopathology.
Nat Hum Behav 2020; 4: 811–18.

Responsible editorYing Yuyan