Elsevier

The Lancet Psychiatry

Volume 3, Issue 4, April 2016, Pages 342-349
The Lancet Psychiatry

Articles
Childhood maltreatment and unfavourable clinical outcomes in bipolar disorder: a systematic review and meta-analysis

https://doi.org/10.1016/S2215-0366(15)00544-1Get rights and content

Summary

Background

Bipolar disorder affects up to one in 25 individuals and identification of early risk indicators of negative outcomes could facilitate early detection of patients with greatest clinical needs and risk. We aimed to investigate the association between childhood maltreatment and key negative outcomes in patients with bipolar disorder.

Methods

For this systematic review and meta-analysis we searched MEDLINE, PsycINFO, and Embase to identify articles published before Jan 1, 2015, examining the association of maltreatment (physical, sexual, or emotional abuse, neglect, or family conflict) before age 18 years with clinical features and course of illness in bipolar disorder. Data were extracted from published reports and any missing information was requested from investigators. We did 12 independent random-effects meta-analyses to quantify the associations between childhood maltreatment and course of illness or clinical features.

Findings

We initially identified 527 records and after unsuitable studies were removed, our search yielded 148 publications of which 30 were used in the meta-analysis. Patients with bipolar disorder and history of childhood maltreatment had greater mania severity (six studies, 780 participants; odds ratio [OR] 2·02, 95% CI 1·21–3·39, p=0·008), greater depression severity (eight studies, 1007 participants; 1·57, 1·25–1·99, p=0·0001), greater psychosis severity (seven studies, 1494 participants; 1·49, 1·10–2·04, p=0·011), higher risk of comorbidity with post-traumatic stress disorder (eight studies, 2494 participants; 3·60, 2·45–5·30, p<0·0001), anxiety disorders (seven studies, 5091 participants; 1·90, 1·39–2·61, p<0·0001), substance misuse disorders (11 studies, 5469 participants; 1·84, 1·41–2·39, p<0·0001), alcohol misuse disorder (eight studies, 5040 participants; 1·44, 1·13–1·83, p=0·003), earlier age of bipolar disorder onset (14 studies, 5733 participants; 1·85, 1·43–2·40, p<0·0001), higher risk of rapid cycling (eight studies, 3010 participants; 1·89, 1·45–2·48, p<0·0001), greater number of manic episodes (seven studies, 3909 participants; 1·26, 1·09–1·47, p=0·003), greater number of depressive episodes (eight studies, 4025 participants; 1·38, 1·07–1·79, p=0·013), and higher risk of suicide attempt (13 studies, 3422 participants; 2·25, 1·88–2·70, p<0·0001) compared with those with bipolar disorder without childhood maltreatment. Overall, these associations were not explained by publication bias, undue effects of individual studies, or variation in study quality.

Interpretation

Childhood maltreatment predicts unfavourable clinical features and course of illness in patients with bipolar disorder.

Funding

None.

Introduction

Bipolar disorder is an impairing, progressive illness affecting up to one in 25 individuals.1, 2, 3, 4, 5 The diagnosis encompasses a full range of chronic mood disorders with heterogeneous clinical presentation and longitudinal course.6, 7 In this heterogeneous clinical group, identification of early risk indicators of negative outcome is essential to deliver stratified early interventions and to improve prognosis.6, 7

Previous research has identified measures of negative clinical outcome.7 Patients with bipolar disorder who have severe symptoms,8 comorbid anxiety disorders,9, 10 and substance or alcohol misuse disorders11 have the poorest clinical course as characterised by early onset of disease, rapid cycling, and a large number of manic and depressive episodes. In turn, patients with a poor course of illness are at increased risk of completed suicide (in 10–15% of people with bipolar disorder) and non-suicidal self-injury (20–60%), which are tragically prevalent in this population.12, 13, 14, 15

We did a meta-analysis to test whether a history of childhood maltreatment is associated with a heightened risk of the previously stated correlated measures of negative outcomes in patients with bipolar disorder and, thus, might be used as an early indicator of disease progression. A priori support for these associations was based on findings that maltreatment is highly prevalent, affecting up to 57% of patients with bipolar disorder,16 predicts a doubled risk of unfavourable course of illness in unipolar depression,17 is associated with biological abnormalities that could contribute to bipolar disorder progression (eg, systemic inflammation),18, 19, 20, 21, 22, 23 and has been connected to several of the previously stated outcomes in qualitative literature reviews.24, 25, 26 We used meta-analytical techniques to gain sufficient statistical power in the context of the comparative low prevalence of bipolar disorder, to quantitatively summarise the associations of childhood maltreatment with course of illness and clinical features in bipolar disorder in published studies, to examine the heterogeneity of findings in the published literature, and to test various possible sources of bias or artifacts.

Research in context

Evidence before this study

We searched MEDLINE, PsycINFO, and Embase databases for articles in English and published before Jan 1, 2015, that tested the association of childhood maltreatment with clinical features and course of illness in bipolar disorder, using the search terms “child* abuse”, “child* neglect”, “child* maltreatment”, “early abuse”, “early maltreatment”, “early neglect”, “sexual abuse”, “physical abuse”, “emotional abuse”, and “family conflict” in combination with “bipolar”, “mania/manic”, “hypomania/hypomanic”, “cyclothymia/cyclothymic”, and “manic depress*”. After excluding duplicates or unsuitable reports, we identified 30 studies that tested the association of a history of childhood maltreatment with 12 correlated clinical outcomes in patients with bipolar disorder.

Added value of this study

From our 12 independent meta-analyses, we showed that, compared with patients with bipolar disorder who did not experience childhood maltreatment, patients with bipolar disorder and a history of childhood maltreatment had greater mania severity, greater depression severity, greater psychosis severity, higher risk of comorbidity with post-traumatic stress disorder, anxiety disorders, substance misuse disorders, and alcohol misuse disorder, earlier age of bipolar disorder onset, higher risk of rapid cycling, greater number of manic episodes, greater number of depressive episodes, and higher risk of suicide attempt. Effect sizes varied across outcomes with odds ratios of 1·26 to 3·60. Overall, these associations were not accounted for by artifacts owing to publication bias, undue effect of individual studies, or variation in study quality.

Implications of all the available evidence

Results suggest that a history of childhood maltreatment can be used as an indicator for disease progression to identify patients with bipolar disorder who are at a higher risk of unfavourable clinical features and course of illness. Additional research is needed to test whether a history of childhood maltreatment can be used as an indicator for unfavourable treatment outcomes. Further research on the stratified, and possibly trans-diagnostic, biological abnormalities associated with a history of childhood maltreatment could uncover innovative treatment strategies.

Section snippets

Search strategy and selection criteria

We did a systematic review and meta-analysis in accordance with the PRISMA and MOOSE guidelines (appendix).

We searched MEDLINE, PsycINFO, and Embase databases for articles written in English and published before Jan 1, 2015, that tested the association of childhood maltreatment with clinical features and course of illness in bipolar disorder. We searched using the following terms: “child* abuse”, “child* neglect”, “child* maltreatment”, “early abuse”, “early maltreatment”, “early neglect”,

Results

We initially identified 527 records. After removal of unsuitable studies, our search yielded 148 publications, of which 30 were used in the meta-analysis (figure 1). A description of included studies16, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66 is in the appendix. We undertook 12 independent meta-analyses for each of the clinical outcomes in bipolar disorder; table 1 and figure 2 summarise these results. Individual forest

Discussion

Our meta-analysis showed that a history of childhood maltreatment in patients with bipolar disorder is associated with a heightened risk of severity of manic, depressive, and psychotic symptoms, risk of comorbid PTSD, anxiety, substance or alcohol misuse disorders, early age of bipolar disorder onset, risk of rapid cycling, number of manic and depressive episodes, and risk of suicide attempt. Overall, these associations were not accounted for by artifacts owing to publications bias, undue

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