Childhood trauma and mixed episodes are associated with poor response to lithium in bipolar disorders

Étain, Bruno; Lajnef, Mohamed; Brichant‐Petitjean, Clara; Geoffroy, Pierre Alexis; Henry, Chantal; Gard, Sébastien; Kahn, Jean‐Pierre; Leboyer, Marion; Young, Allan H.; Bellivier, Frank

doi:10.1111/acps.12684

Cited by 46 publications

(53 citation statements)

References 55 publications

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“…Insulin resistance was found to be associated with poor response to lithium in one study, in keeping with the studies showing an association with BMI . While we did not consider childhood trauma as a ‘clinical’ predictor of treatment response, one included study examined this among other features . This study suggested physical abuse was an independent predictor of poor lithium response after accounting for many clinical characteristics.…”

Section: Resultssupporting

confidence: 71%

A systematic review and meta‐analysis of clinical predictors of lithium response in bipolar disorder

Hui¹,

Kandola²,

Shen³

et al. 2019

Acta Psychiatr Scand

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Objective To determine clinical predictors of lithium response in bipolar disorder. Methods Systematic review of studies examining clinical predictors of lithium response was conducted. Meta‐analyses were performed when ≥2 studies examined the same potential predictor. Results A total of 71 studies, including over 12 000 patients, identified six predictors of good response: mania‐depression‐interval sequence [odds ratio (OR): 4.27; 95% CI: 2.61, 6.97; P < 0.001], absence of rapid cycling (OR for rapid cycling: 0.30; 95% CI: 0.17, 0.53; P < 0.001), absence of psychotic symptoms (OR for psychotic symptoms: 0.52; 95% CI: 0.34, 0.79; P = 0.002), family history of bipolar disorder (OR: 1.61; 95% CI: 1.03, 2.52; P = 0.036), shorter prelithium illness duration [standardised mean difference (SMD): −0.26; 95% CI: −0.41, −0.12; P < 0.001] and later age of onset (SMD: 0.17; 95% CI: 0.02, 0.36; P = 0.029). Additionally, higher body mass index was associated with poor response in two studies (SMD: −0.61; 95% CI: −0.90, −0.32; P < 0.001). There was weak evidence for number of episodes prior to lithium treatment (SMD: −0.42; 95% CI: −0.84, −0.01; P = 0.046), number of hospitalisations before lithium (SMD: −0.40; 95% CI: −0.81, 0.01; P = 0.055) and family history of lithium response (OR: 10.28; 95% CI: 0.66, 161.26; P = 0.097). Conclusions The relative importance of these clinical characteristics should be interpreted with caution because of potential biases and confounding.

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Section: Resultssupporting

confidence: 71%

A systematic review and meta‐analysis of clinical predictors of lithium response in bipolar disorder

Hui¹,

Kandola²,

Shen³

et al. 2019

Acta Psychiatr Scand

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“…Childhood maltreatment might lead to greater instability through a resistance to mood stabilizers, especially when a lower response to lithium has been reported to be associated with childhood maltreatment . 22 Childhood maltreatment might also lead to a greater risk of rapid cycling, through more depressive episodes (mediation effect), that are more likely to be then treated with antidepressants which are a classical risk factor for rapid cycling in BD. 34 For those cases with high genetic risk, the association between childhood maltreatment and a more unstable clinical profile (greater risk for rapid cycling) is lost.…”

Section: Discussionmentioning

confidence: 99%

“…Several clinical variables were collected during the clinical assessment and selected a priori: age at onset, number of episodes (based on manic and depressive episodes), lifetime presence of mixed episode, of psychotic features during mood episodes, of rapid cycling, of substance abuse disorder and of suicide attempt. These clinical variables were selected for the following reasons: (a) they are indicators of the complexity and/or severity of the clinical expression of BD; and (b) they have been associated with childhood trauma in two previous study from our groups and a recent meta‐analysis …”

Section: Methodsmentioning

confidence: 99%

“…The study sample comes from Norway and France, as described in previous publications. 19,20 All participants in the study were These clinical variables were selected for the following reasons: (a) they are indicators of the complexity and/or severity of the clinical expression of BD; and (b) they have been associated with childhood trauma in two previous study from our groups 20,22 and a recent meta-analysis. 8 The two sites used the same definition of age at onset as the age when the subject first met DSM-IV criteria for a major depressive, manic, hypomanic or mixed episode.…”

Section: Clinical Assessmentmentioning

confidence: 99%

See 1 more Smart Citation

Childhood maltreatment and polygenic risk in bipolar disorders

et al. 2019

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Background Childhood maltreatment is a well‐known risk factor for developing a more severe and complex form of bipolar disorders (BD). However, knowledge is scarce about the interactions between childhood maltreatment and underlying genetic vulnerability on the clinical expression of BD. Method We assigned a BD‐polygenic risk score (BD‐PRS), calculated from the Psychiatric Genomics Consortium, to each individual in a sample of 402 cases with BD. The lifetime clinical expression of BD was characterized using structured interviews and patients completed the Childhood Trauma Questionnaire (CTQ) to assess the severity of childhood maltreatment. Results Cases who reported more severe childhood maltreatment had a lower BD‐PRS (rho = −0.12, P = .01), especially when considering emotional abuse (rho = −0.16, P = .001). An interaction between BD‐PRS and childhood maltreatment was observed for the risk of rapid cycling (P = .01). No further interactions between BD‐PRS and childhood maltreatment were observed for other clinical characteristics (age at onset, suicide attempts, number of mood episodes, mixed features, substance use disorders and psychotic symptoms). Conclusion Our study is the first to show that less genetic risk may be needed to develop a more unstable form of BD when exposed to childhood maltreatment. Our study supports childhood trauma as an independent risk factor for BD.

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“…21 Childhood maltreatment also markedly increases the severity of the expression of BD, leading to earlier, more suicidal and recurrent forms of the disorder 22 , and lower response to conventional mood stabilizers. 23 Childhood maltreatment also interacts with cannabis use during adolescence to increase the severity of the clinical expression of BD. 24,25 Childhood trauma might lead to BD by modifying amygdala volume and prefrontolimbic functional connectivity.…”

mentioning

confidence: 99%