Is a Specific Subtype of Childhood Trauma Driving the Association Between Childhood Trauma and Clinical Characteristics?
Multilevel regression analyses were performed to investigate whether specific underlying childhood trauma subtypes were driving the associations with clinical characteristics (Table 3). Only sexual abuse and emotional abuse were independently associated with earlier age at onset. Moreover, as shown in step 2, this association was still significant after gender was added into the model. Emotional and sexual abuse were independently associated with increased frequency of a history of suicide attempt and remained so after gender and duration of illness were introduced into the model. Sexual abuse was the only statistically significant predictor of rapid cycling. Sexual abuse was still associated with rapid cycling after gender and duration of illness were added into the model.
Table 3
CLICK FIGURE TO ENLARGE
We performed an additional post hoc analysis correcting for recruitment site, as the French sample had a slightly higher number of rapid-cycling subjects than the Norwegian sample, and the Norwegian sample had a slightly lower age at onset than the French sample. Reassuringly, after we corrected for recruitment site, sexual abuse was still significantly associated with rapid cycling (P = .006), and sexual abuse (P = .002) and emotional abuse (P = .002) were significantly associated with earlier age at onset (data not shown). Last, we performed a multivariate analysis controlling for alcohol and cannabis use, and our results remained the same.
DISCUSSION
Our study demonstrated robust associations between a more severe clinical presentation and childhood adverse events in a large, thoroughly described sample of bipolar disorder patients with the use of a broad range of childhood trauma variables, including neglect (both emotional and physical) and emotional, physical, and sexual abuse. Our results show that childhood traumatic events are associated with a more severe form of bipolar disorder characterized by earlier onset of the illness, greater prevalence of a history of suicide attempt, rapid cycling, greater proneness toward depression, and more cannabis use. We found a clear dose-response effect of abuse on all of these clinical variables, in the direction of an association of increased trauma with more severe clinical expression. The current findings also include gender differences, which have not been observed before.
Across clinical characteristics, our results demonstrate that the association of childhood trauma is stronger for abuse (emotional, physical, and sexual) than neglect (emotional and physical). The effect observed for neglect seems to be driven by an underlying effect of abuse, specifically emotional abuse. This suggests that the trauma probably must reach a certain level of intensity (abuse vs neglect and at least a moderate to severe intensity) to have an effect on the phenotype. Indeed, a unidirectional relation can be observed between abuse and neglect, with the abuse increasing the relative risk for being exposed to neglect (the inverse being false). For example, we observed a relationship between neglect and higher prevalence of at least 1 suicide attempt (P = .02); however, this effect disappeared when other types of trauma were entered into a multivariate model, and only emotional and sexual abuse remained significantly associated with suicide attempt.
Regarding the effect of individual specific subtypes of abuse, we found that sexual abuse was the strongest predictor of rapid cycling, while both emotional and sexual abuse were related to lower age at onset and to suicide attempts. There are some indications that physical abuse is associated more with psychosis, and emotional abuse, with bipolar disorder, while sexual abuse might be associated more with impulsivity dyscontrol.1,5 Sexual abuse does not seem to be strongly associated with psychosis,28 but rather with suicide attempt.29 Indeed, emotional abuse is increased in patients with bipolar disorder, also after correcting for other types of abuse, compared to healthy controls.1,5 It might be that emotional abuse is specifically linked to bipolar disorder based on possible links to emotional dysregulation, which is a core symptom of bipolar disorder. We could hypothesize that emotional abuse and sexual abuse are associated with development of emotional dysregulation, which may be an underlying core link between childhood trauma and increased symptomatology in bipolar disorder patients; the link could be mediated by intermediate dimensions such as increased affective dysregulation5 or impulsivity.30 We suggest further investigation of this in future studies.
Females reported greater frequency of trauma, as well as greater associations with clinical characteristics of bipolar disorder, than males. Females with childhood trauma showed stronger associations with earlier onset of illness, rapid cycling, suicide attempts, and more depressive episodes than males with trauma. We therefore performed additional analyses controlling for gender to rule out that female patients drove the association between childhood trauma and the development of more severe clinical characteristics in bipolar disorder. The results remained the same, indicating an additive effect of gender, as well as a significant gender-nonspecific effect of childhood trauma, on clinical characteristics in bipolar disorder.
Lastly, future research should investigate the mechanisms behind associations between childhood trauma and clinical symptomatology in bipolar disorder, such as the link between childhood trauma and substance abuse. As already mentioned, childhood trauma has been related to an increased risk of substance abuse,31 and patients with bipolar disorder show a higher frequency of substance abuse compared to the general population.32 In bipolar disorder, substance abuse is associated with increased sensitization and vulnerability to recurrent episodes, thus possibly driving illness progression.33 It would therefore be of interest to investigate if substance abuse is moderating the effect of childhood trauma on clinical characteristics in bipolar disorder. Moreover, we know that bipolar disorder is highly heritable; to further investigate how genetic variants may moderate the effect of childhood trauma on clinical expressions of bipolar disorder would be of great interest. Bipolar disorder is determined by both genetic and environmental risk factors, with interactions between factors remaining to be clarified.34 Some attempts have been made to explore such an issue in bipolar disorder with, for example, interactions between BDNF gene variants and early life stress on bipolar course.35 Future studies will focus on identifying how some genetic susceptibility factors are likely to moderate the effects of childhood trauma on the clinical expression of the disorder.
With regard to study limitations, first, data on childhood trauma were, as in most clinical studies of this phenomenon, obtained retrospectively, with the inherent weakness of retrospective reporting designs. However, the retrospective collection of childhood trauma data in patients with severe mental disorders has been found a valid and reliable source of information in previous studies.2 Our study fulfills the quality criteria of Fisher and Hosang,16 with the limitation that in the Norwegian sample no standardized assessment, but rather clinical judgment, was used to decide whether patients were in a suitable mood to reliably fill in the CTQ form; all patients from the French sample were systematically evaluated and defined as euthymic at time of assessment. Another limitation of using the CTQ is that it does not identify all types of traumas, such as childhood traumas due to early parental loss, divorce, natural disasters, house fires, and so on. As a result, these kinds of childhood traumas are left out of the multivariate analysis, yet may explain some of the dependent variables. Also, not assessing for these traumas may lead to misclassification of cases and noncases, with some who may have had 1 or more of these other traumas still being classified as not having an early trauma using the CTQ form. However, although the CTQ has its limitations, it is a well-used questionnaire in the literature, which improves the possibility of comparing findings across studies. We cannot rule out, though, that some patients may have experienced other types of traumas not assessed here.
Moreover, we have previously reported that in bipolar disorder, substance abuse is associated with increased sensitization and vulnerability to recurrent episodes, thus possibly driving illness progression.33 Substance abuse has also been linked to a possibly worse course of illness (increased risk of suicide, lower age at onset, rapid cycling).36–38 We also know that there is a high correlation between childhood trauma and substance use,39,40 and although we performed additional multivariate analyses controlling for lifetime cannabis and alcohol abuse, the association between substance abuse, childhood trauma, and bipolar symptomatology should be further investigated. It may also be that disorders comorbid with bipolar disorder, such as anxiety disorders, are driving some of the effects we see; for example, anxiety disorders have been associated with suicidality.41 Unfortunately, we do not have complete data on comorbid diagnoses and have therefore not included them as possible confounders in our analyses. Finally, clinical variables were assessed using the SCID-I or the DIGS. Reliability analysis comparing DIGS and DSM criteria has shown excellent reliability scores for bipolar disorders,19 indicating that use of the DIGS did not bias our results.
The main strength of this study is the large sample size, which provided the power to investigate gender differences, as well as made it possible to perform multilevel
Is a Specific Subtype of Childhood Trauma Driving the Association Between Childhood Trauma and Clinical Characteristics?
Multilevel regression analyses were performed to investigate whether specific underlying childhood trauma subtypes were driving the associations with clinical characteristics (Table 3). Only sexual abuse and emotional abuse were independently associated with earlier age at onset. Moreover, as shown in step 2, this association was still significant after gender was added into the model. Emotional and sexual abuse were independently associated with increased frequency of a history of suicide attempt and remained so after gender and duration of illness were introduced into the model. Sexual abuse was the only statistically significant predictor of rapid cycling. Sexual abuse was still associated with rapid cycling after gender and duration of illness were added into the model.
Table 3
CLICK FIGURE TO ENLARGE
We performed an additional post hoc analysis correcting for recruitment site, as the French sample had a slightly higher number of rapid-cycling subjects than the Norwegian sample, and the Norwegian sample had a slightly lower age at onset than the French sample. Reassuringly, after we corrected for recruitment site, sexual abuse was still significantly associated with rapid cycling (P = .006), and sexual abuse (P = .002) and emotional abuse (P = .002) were significantly associated with earlier age at onset (data not shown). Last, we performed a multivariate analysis controlling for alcohol and cannabis use, and our results remained the same.
DISCUSSION
Our study demonstrated robust associations between a more severe clinical presentation and childhood adverse events in a large, thoroughly described sample of bipolar disorder patients with the use of a broad range of childhood trauma variables, including neglect (both emotional and physical) and emotional, physical, and sexual abuse. Our results show that childhood traumatic events are associated with a more severe form of bipolar disorder characterized by earlier onset of the illness, greater prevalence of a history of suicide attempt, rapid cycling, greater proneness toward depression, and more cannabis use. We found a clear dose-response effect of abuse on all of these clinical variables, in the direction of an association of increased trauma with more severe clinical expression. The current findings also include gender differences, which have not been observed before.
Across clinical characteristics, our results demonstrate that the association of childhood trauma is stronger for abuse (emotional, physical, and sexual) than neglect (emotional and physical). The effect observed for neglect seems to be driven by an underlying effect of abuse, specifically emotional abuse. This suggests that the trauma probably must reach a certain level of intensity (abuse vs neglect and at least a moderate to severe intensity) to have an effect on the phenotype. Indeed, a unidirectional relation can be observed between abuse and neglect, with the abuse increasing the relative risk for being exposed to neglect (the inverse being false). For example, we observed a relationship between neglect and higher prevalence of at least 1 suicide attempt (P = .02); however, this effect disappeared when other types of trauma were entered into a multivariate model, and only emotional and sexual abuse remained significantly associated with suicide attempt.
Regarding the effect of individual specific subtypes of abuse, we found that sexual abuse was the strongest predictor of rapid cycling, while both emotional and sexual abuse were related to lower age at onset and to suicide attempts. There are some indications that physical abuse is associated more with psychosis, and emotional abuse, with bipolar disorder, while sexual abuse might be associated more with impulsivity dyscontrol.1,5 Sexual abuse does not seem to be strongly associated with psychosis,28 but rather with suicide attempt.29 Indeed, emotional abuse is increased in patients with bipolar disorder, also after correcting for other types of abuse, compared to healthy controls.1,5 It might be that emotional abuse is specifically linked to bipolar disorder based on possible links to emotional dysregulation, which is a core symptom of bipolar disorder. We could hypothesize that emotional abuse and sexual abuse are associated with development of emotional dysregulation, which may be an underlying core link between childhood trauma and increased symptomatology in bipolar disorder patients; the link could be mediated by intermediate dimensions such as increased affective dysregulation5 or impulsivity.30 We suggest further investigation of this in future studies.
Females reported greater frequency of trauma, as well as greater associations with clinical characteristics of bipolar disorder, than males. Females with childhood trauma showed stronger associations with earlier onset of illness, rapid cycling, suicide attempts, and more depressive episodes than males with trauma. We therefore performed additional analyses controlling for gender to rule out that female patients drove the association between childhood trauma and the development of more severe clinical characteristics in bipolar disorder. The results remained the same, indicating an additive effect of gender, as well as a significant gender-nonspecific effect of childhood trauma, on clinical characteristics in bipolar disorder.
Lastly, future research should investigate the mechanisms behind associations between childhood trauma and clinical symptomatology in bipolar disorder, such as the link between childhood trauma and substance abuse. As already mentioned, childhood trauma has been related to an increased risk of substance abuse,31 and patients with bipolar disorder show a higher frequency of substance abuse compared to the general population.32 In bipolar disorder, substance abuse is associated with increased sensitization and vulnerability to recurrent episodes, thus possibly driving illness progression.33 It would therefore be of interest to investigate if substance abuse is moderating the effect of childhood trauma on clinical characteristics in bipolar disorder. Moreover, we know that bipolar disorder is highly heritable; to further investigate how genetic variants may moderate the effect of childhood trauma on clinical expressions of bipolar disorder would be of great interest. Bipolar disorder is determined by both genetic and environmental risk factors, with interactions between factors remaining to be clarified.34 Some attempts have been made to explore such an issue in bipolar disorder with, for example, interactions between BDNF gene variants and early life stress on bipolar course.35 Future studies will focus on identifying how some genetic susceptibility factors are likely to moderate the effects of childhood trauma on the clinical expression of the disorder.
With regard to study limitations, first, data on childhood trauma were, as in most clinical studies of this phenomenon, obtained retrospectively, with the inherent weakness of retrospective reporting designs. However, the retrospective collection of childhood trauma data in patients with severe mental disorders has been found a valid and reliable source of information in previous studies.2 Our study fulfills the quality criteria of Fisher and Hosang,16 with the limitation that in the Norwegian sample no standardized assessment, but rather clinical judgment, was used to decide whether patients were in a suitable mood to reliably fill in the CTQ form; all patients from the French sample were systematically evaluated and defined as euthymic at time of assessment. Another limitation of using the CTQ is that it does not identify all types of traumas, such as childhood traumas due to early parental loss, divorce, natural disasters, house fires, and so on. As a result, these kinds of childhood traumas are left out of the multivariate analysis, yet may explain some of the dependent variables. Also, not assessing for these traumas may lead to misclassification of cases and noncases, with some who may have had 1 or more of these other traumas still being classified as not having an early trauma using the CTQ form. However, although the CTQ has its limitations, it is a well-used questionnaire in the literature, which improves the possibility of comparing findings across studies. We cannot rule out, though, that some patients may have experienced other types of traumas not assessed here.
Moreover, we have previously reported that in bipolar disorder, substance abuse is associated with increased sensitization and vulnerability to recurrent episodes, thus possibly driving illness progression.33 Substance abuse has also been linked to a possibly worse course of illness (increased risk of suicide, lower age at onset, rapid cycling).36–38 We also know that there is a high correlation between childhood trauma and substance use,39,40 and although we performed additional multivariate analyses controlling for lifetime cannabis and alcohol abuse, the association between substance abuse, childhood trauma, and bipolar symptomatology should be further investigated. It may also be that disorders comorbid with bipolar disorder, such as anxiety disorders, are driving some of the effects we see; for example, anxiety disorders have been associated with suicidality.41 Unfortunately, we do not have complete data on comorbid diagnoses and have therefore not included them as possible confounders in our analyses. Finally, clinical variables were assessed using the SCID-I or the DIGS. Reliability analysis comparing DIGS and DSM criteria has shown excellent reliability scores for bipolar disorders,19 indicating that use of the DIGS did not bias our results.
The main strength of this study is the large sample size, which provided the power to investigate gender differences, as well as made it possible to perform multilevel
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