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Childhood traumatic experiences of patients with bipolar disorder type I and type II
Journal of Affective Disorders 175 (2015) 92–97
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Research report
Childhood traumatic experiences of patients with bipolar disorder type I and type II Delfina Janiri a,b,c, Gabriele Sani a,b,c, Emanuela Danese a,b, Alessio Simonetti a,b,c, Elisa Ambrosi a,b, Gloria Angeletti a,b,c, Denise Erbuto b, Carlo Caltagirone a,d, Paolo Girardi a,b,c, Gianfranco Spalletta a,n a
IRCCS Santa Lucia Foundation, Neuropsychiatry Laboratory, Department of Clinical and Behavioral Neurology, Rome, Italy NESMOS Department (Neurosciences, Mental Health, and Sensory Organs), Sapienza University of Rome, School of Medicine and Psychology, Sant'Andrea Hospital, Rome, Italy c Centro Lucio Bini, Rome, Italy d Department of Medicine of Systems, Tor Vergata University of Rome, Italy b
art ic l e i nf o
a b s t r a c t
Article history: Received 10 August 2014 Received in revised form 20 December 2014 Accepted 24 December 2014 Available online 31 December 2014
Background: Childhood trauma is an important environmental stressor associated with bipolar disorders (BD). It is still not clear if it is differently distributed between BD I and BD II. Therefore, the aim of this research was to investigate the distribution patterns of childhood trauma in BD I and BD II. In this perspective, we also studied the relationship between childhood trauma and suicidality. Methods: We assessed 104 outpatients diagnosed with BD I (n ¼58) or BD II (n ¼46) according to DSMIV-TR criteria and 103 healthy controls (HC) matched for age, sex and education level. History of childhood trauma was obtained using the Childhood Trauma Questionnaire (CTQ). Results: All patients with BD had had more severe traumatic childhood experiences than HC. Both BD I and BD II patients differed significantly from HC for trauma summary score and emotional abuse. BD I patients differed significantly from HC for sexual abuse, and BD II differed from HC for emotional neglect. BD I and BD II did not significantly differ for any type of trauma. Suicide attempts were linked to both emotional and sexual abuse in BD I and only to emotional abuse in BD II. Emotional abuse was an independent predictor of lifetime suicide attempts in BD patients. Limitations: The reliability of the retrospective assessment of childhood trauma experiences with the CTQ during adulthood may be influenced by uncontrolled recall bias. Conclusions: The assessment of childhood trauma, which has great clinical importance because of its strong link with suicidality, can unveil slight differences between BD subtypes and HC. & 2014 Elsevier B.V. All rights reserved.
Keywords: Childhood trauma Bipolar disorders Suicide
1. Introduction Life events can significantly influence the clinical presentation of mood disorders (Kraepelin, 1899; Post, 1992). In particular, several studies consistently show that childhood trauma is a relevant environmental stressor associated with bipolar disorders (BD) (Bücker et al., 2014; Garno et al., 2005; Romero et al., 2009). Even though childhood trauma is more frequent in BD patients, considered as an homogeneous group, than in healthy control (HC) subjects (Etain et al., 2010; Watson et al., 2013), it is still not clear whether its occurrence is differently distributed in BD I and BD II. n Correspondence to: IRCCS Santa Lucia Foundation, Neuropsychiatry Laboratory, Department of Clinical and Behavioral Neurology,Via Ardeatina, 306 00179 Rome, Italy. Tel./fax: þ 0039 06 51501575. E-mail address: [email protected] (G. Spalletta).
http://dx.doi.org/10.1016/j.jad.2014.12.055 0165-0327/& 2014 Elsevier B.V. All rights reserved.
Childhood trauma can influence clinical outcome by inducing earlier disease onset, a greater number of episodes, a rapid cycling course and suicide attempts and increasing the need for hospitalization. Finally, specific types of childhood trauma are associated with different clinical features, (Daruy‐Filho et al., 2011) like suicide attempts (Carballo et al., 2008; Leverich et al., 2002). Specifically, previous studies found that suicide attempts are associated with both sexual and emotional abuse (Garno et al., 2005; Etain et al., 2013). In this study our main aim was to investigate how different types of childhood trauma are associated with the two subtypes of BD. We also investigated their influence on suicidality. We predicted that distinct types of childhood trauma would be associated with suicide attempts in different types of BD. We also investigated whether diagnosis of BD I or BD II subtypes modifies the relationship between childhood trauma and suicidality. We predicted that the effect of
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childhood trauma on suicidality might be more important than the categorical distinction between BD subtypes.
2. Materials and method 2.1. Participants We assessed 104 outpatients who had been diagnosed with BD I (n ¼58) and BD II (n ¼46) according to the DSM-IV-TR criteria (American Psychiatric Association., 2000) at the IRCCS Santa Lucia Foundation in Rome, Italy. All patients were initially recruited at two sites: Sant'Andrea Hospital and Santa Lucia Foundation in Rome. Subjects were screened for DSM-IV-TR Axis I disorders and clinical diagnoses were confirmed using the Structured Clinical Interview for DSM-IV-TR axis I Disorders, patient edition (SCID-I/P) (First et al., 2002a), conducted by trained raters. In addition to a diagnosis of BD, inclusion criteria were; (i) no additional axis I and II diagnoses evaluated by the structured interview SCID I/P and SCID-II (First et al., 1997); (ii) at least five years of education; (iii) no history of substance abuse during the last one year period evaluated by the structured interview SCID I/P. Exclusion criteria were: (i) traumatic head injury with loss of consciousness; (ii) lifetime history of major medical or neurological disorders; (iii) suspected cognitive impairment based on a Mini-Mental State Examination (MMSE) (Folstein et al., 1975) score lower than 24, consistent with normative data of the Italian population (Measso et al., 1993). (iv) non-Italian language native speaker; (v) any potential brain abnormality and microvascular lesion apparent on conventional FLAIR-scans. The presence, severity, and location of vascular lesions was computed using the semiautomated method recently published by our group (Iorio et al., 2013). All patients had been under stable pharmacological treatment for at least six months. We recruited 103 healthy controls (HC) from the same geographical area. All HC were screened for a current or lifetime history of DSM-IV-TR Axis I and II disorders using the SCID-I/NP (First et al., 2002b) and SCID-II (First et al., 1997). For the aims of this study, they were also interviewed to determine whether they had suicidal behavior; none reported lifetime suicidal behavior. They were also assessed to verify whether any first-degree relative was affected by mood disorders or schizophrenia. If they had a positive family history they were excluded. Exclusion criteria were the same as those for the patient group. The study was approved and undertaken in accordance with the guidelines of the Santa Lucia Foundation Ethics Committee and in accordance with the Principles of Human Rights, as adopted by the World Medical Association at the 18th WMA General Assembly, Helsinki, Finland, June 1964 and subsequently amended at the 64th WMA General Assembly, Fortaleza, Brazil, October 2013. All participants gave their written informed consent to participate in the research after they had received a complete explanation of the study procedures. 2.2. Clinical assessment We used the short form of the Childhood Trauma Questionnaire (CTQ) to measure adverse childhood events. This is a 28item, retrospective, self-report questionnaire (Bernstein et al., 2003) that investigates traumatic experiences in childhood; there are five possible answers, which range from “never true” to “very often true” depending on the frequency of the events. The questionnaire assesses five types of trauma: emotional abuse, emotional neglect, physical abuse, physical neglect and sexual abuse. For each type of trauma scores range from 5 to 25. A summary score (ranging from 25 to 125) is also calculated. Higher scores indicate greater childhood mistreatment. The CTQ has been
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used in both non-clinical (Scher et al., 2001) and clinical populations (Martinotti et al., 2009; Uçok and Bikmaz, 2007). It has a high degree of reliability (Bernstein et al., 1994) and it was also recently used to assess patients with affective disorders (Etain et al., 2010; Garno et al., 2005; Polanczyk et al., 2009). Psychopathology was rated using the Young Mania Rating Scale (YMRS) for mania symptom severity (Young et al., 1978), the 17-item Hamilton Rating Scale for Depression (HAMD) for depression symptom severity (Hamilton, 1960) and the Hamilton Rating Scale for Anxiety (HAMA) for anxiety symptom severity (Hamilton, 1959); all investigated the week prior to the assessment. All HC scored under the cut-off on the HAMD, YMRS and HAMA. Clinical characteristics were collected during a clinical interview. Psychotic features were evaluated with two items (i.e., item 1 “Delusions” and item 3 “Hallucinations”) of the Positive and Negative Symptoms scale (PANSS) (Kay et al., 1987), which are related to the moment of the evaluation and to the entire life. Suicidal ideation and suicidal attempts were assessed with a semistructured questionnaire consisting of two parts, one related to the past 6 months and the other to the lifetime (to the entire life). Each part included three questions: “Have you ever seriously thought about committing suicide?” “Have you ever made a plan for committing suicide?” “Have you ever attempted suicide?”. Respondents had to answer only “Yes” or “No”. Attempters then had to answer questions about their attempts: “How many time did you attempt suicide?” and “Can you briefly describe how you attempted suicide?”. From their responses to the last question we classified attempts as violent suicide attempts (defenestration, hanging, use of knives or fire arms) or non violent suicide attempts and as serious suicide attempts (requiring medical attention) or non serious suicide attempts.
2.3. Statistical analyses We compared the three groups' (i.e. BD I, BD II and HC) sociodemographic and clinical characteristics on the basis of the chisquare test for nominal variables and one-way analysis of variance (ANOVA) followed by post-hoc Scheffé tests for continuous variables and by pairwise post-hoc analyses for nominal variables. For the aims of this study, we focused on the distribution patterns of childhood trauma subtypes in BD I and BD II. First, we conducted a series of one-way ANOVAs, followed by Scheffé posthoc tests, to compare means among groups. The level of significance was set at p o0.05 for the ANOVA comparative measurements. To minimize the likelihood of type I errors, the ANOVAs were preceded by overall multivariate analysis of variance (MANOVA) using all of the continuous variables considered in each of the analyses as dependent variables. Second, we investigated the relationship between suicidality and childhood trauma subtypes by considering the previously found distribution patterns. Therefore, after having split our sample by diagnosis, we used a series of one-way ANOVAs to detect differences in means between groups of patients with a history of suicide attempts and patients without a history of suicide attempts, with the level of significance set at po 0.05. Prior to the ANOVAs, we carried MANOVAs using all the continuous variables considered in each of the analyses as dependent variables. To better identify the variables that significantly differentiated BD patients who had or had not made lifetime suicide attempts (considered as the dependent variable), a multivariate logistic regression model was used to estimate the odds of independent variables that differed significantly at a p o0.05 level. We included the BD and childhood trauma subtypes as independent variables to investigate whether the distinction between different BD diagnoses modifies the relationship between CTQ and suicidality.
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Table 1 Sociodemographic and clinical characteristics of BD I, BD II and HC.
χ2
Characteristics
BP I (n¼ 58)
BP II (n¼ 46)
HC (n¼ 103)
F or
Age (years): mean 7(SD) Males: n (%) Educational Level (years): mean7 (SD) Duration of illness (years): mean 7(SD) Number of past episodes: mean 7 (SD) Number of past depressive episodes: mean 7 (SD) Presence of life time suicide attempts: n (%) Presence of life time psychotic symptoms: n (%) HAMD score: mean 7 (SD) YMRS score: mean 7 (SD) HAMA score: mean 7 (SD)
43.93 (13.55) 39 (67.24) 13.82 (3.42) 16.58 (13.06) 10.35 (12.57) 5.10 (5.97) 12 (20.69) 49 (84.48) 7.41 (5.89) 8.15 (9.28) 8.77 (6.88)
46.32 (13.69) 23 (50.00) 14.41 (3.32) 17.63 (12.27) 11.51 (10.07) 5.26 (4.40) 14 (30.43) 4 (8.69) 9.54 (6.63) 3.73 (3.48) 11.15 (6.58)
44.26 (15.68) 54 (52.42) 14.33 (3.52) – – –
0.40 4.18 0.49 0.17 0.19 0.02 1.29 58.96 2.99 9.35 3.17
– – – –
df
p
2 2 2 1 1 1 1 1 1 1 1
0.66 0.12 0.60 0.67 0.66 0.88 0.25 o .0001 0.08 0.0028 0.07
BD I ¼Patients with bipolar disorder type I; BD II ¼Patients with bipolar disorder type II; HC ¼ Healthy controls; SD ¼Standard deviation; df ¼Degrees of freedom; HAMD ¼Hamilton Depression Rating Scale; HAMA¼ Hamilton Anxiety Rating Scale; YMRS¼ Young Mania R Scale Table 2 Distribution patterns of childhood trauma subtypes in BD I and BD II.
Trauma summary score Emotional abuse Physical abuse Sexual abuse Emotional neglect Physical neglect
BD I Mean 7(SD)
BD II Mean 7 (SD)
HC Mean 7 (SD)
F#
df#
P#
HC vs BD I* (p)
HC vs BD II* (p)
BD I vs BD II* (p)
39.13 (12.12) 7.67 (3.67) 6.22 (2.59) 6.37 (2.91) 11.29 (5.44) 7.56 (2.76)
40.89 (10.75) 8.87 (4.40) 6.43 (3.06) 5.91 (1.76) 12.76 (4.95) 6.91 (1.96)
33.09 (7.34) 6.19 (2.10) 5.56 (1.43) 5.19 (0.81) 9.48 (4.49) 6.66 (3.64)
13.27 11.95 3.06 8.11 7.72 1.60
2 2 2 2 2 2
o 0.0001 o 0.0001 0.048 0.0004 0.0006 0.20
0.0009 0.02 0.19 0.0006 0.08 0.20
o 0.0001 o 0.0001 0.09 0.91 0.001 0.89
0.65 0.16 0.89 0.44 0.31 0.56
BD I¼ Patients with bipolar disorder type I; BD II ¼ Patients with bipolar disorder type II; HC ¼ Healthy controls; SD ¼ Standard deviation; df¼ Degrees of freedom. factorial ANOVA
#
n
Scheffé post hoc test
3. Results 3.1. Sociodemographic and clinical characteristics The three groups, i.e., BD I, BD II and HC, did not differ significantly for age, gender or educational level. At the time of clinical assessment patients with BD I obtained significantly higher YMRS scores than patients with BD II (see Table 1). Moreover, the two diagnostic subtypes did not differ for HAMD and HAMA. In the overall group of patients with a diagnosis of BD, 26 reported lifetime suicide attempts (BD I n ¼12, % ¼20.69; BD II n ¼14, % ¼30.43). The mean and the standard deviation (mean7 SD) for the number of suicide attempts in the BD I and the BD II group were 1.75 70.96 and 1.28 7 0.46. BD I and BD II did not significantly differ for the presence of lifetime suicide attempts (see Table 1). Moreover, the two BP subtypes did not differ for the number of suicide attempts. In the overall group of patients, 23 reported that their suicide attempts were serious (BD I n ¼11, % ¼ 91.66; BD II n ¼12, % ¼85.71) and 11 that they were violent (BD I n ¼7, %¼ 58.33; BD II n ¼4, % ¼28.57). BD I and BD II did not significantly differ for these characteristics. In the overall group of patients with a diagnosis of BD, 53 reported lifetime psychotic symptoms (BD I n¼49,%¼84.48; BD II n¼4, %¼ 8.69). Fifty two patients reported delusions (BD I n¼49, %¼ 84.48; BD II n¼3, %¼6.52) and 14 reported hallucinations (BD I: n¼12, %¼20.69; BD II: n¼ 2, %¼ 4.34). BD I differed significantly from BD II concerning the presence of lifetime psychotic symptoms (see Table 1) and for both delusions (χ2 ¼ 62.36; d.f.¼1; p¼ o.0001) and hallucinations (χ2 ¼ 5.88; d.f.¼1; p¼0.01).
experiences on BD diagnostic subtypes. Factorial ANOVAs indicated a main effect of diagnosis on all types of childhood trauma (see Table 2). In particular, a series of pairwise Scheffé post-hoc analyses clarified that both BD I and BD II differed significantly from HC regarding the trauma summary score and emotional abuse. Further, only BD I differed significantly from HC for sexual abuse and only BD II differed significantly from HC for emotional neglect. In all cases, patients with BD suffered more severe trauma experiences than HC (see Table 2). BD I and BD II patients did not significantly differ for any types of childhood trauma. 3.3. Relationship between childhood trauma and lifetime suicide attempts A preliminary MANOVA found a significant global effect (Wilk's Lambda ¼0.78, F¼5.49, df ¼5,98, p ¼0.0002) of childhood traumas on the presence of lifetime suicide attempts (categorized as YES/ NO). As shown Table 3, we found that: (i) the trauma summary score and emotional abuse were more severe in BD I and BD II patients with previous lifetime suicide attempts, and (ii) sexual abuse was more severe in BD I patients with previous lifetime suicide attempts. In the multivariate logistic regression only emotional abuse significantly predicted lifetime suicide attempts. Specifically, the odds (OR ¼ 1.31, 95%CI ¼1.10–1.57; p ¼0.0019) of belonging to the group of BD patients who attempted suicide explained 18.5% of the variance (R2) of the dependent variable.
4. Discussion 3.2. Distribution patterns of childhood trauma subtypes in BD I And BD II A preliminary MANOVA revealed a significant global effect (Wilks' Lambda¼0.82, F¼4.12, df¼ 10, p¼ o0.0001) of childhood trauma
This study was aimed at evaluating how different types of childhood trauma are associated with the two subtypes of BD disorder compared with HC. First, the results show that BD patients (divided into BD I and BD II) reported more childhood traumatic
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Table 3 Relationship between childhood trauma experiences and lifetime suicide attempts. BD I
Trauma summary score Emotional abuse Physical abuse Sexual abuse Physical Neglect Emotional neglect
BD II
Suicide attempts LT Mean (SD)
No Suicide attempts LT Mean (SD)
F
df
p
Suicide attempts LT Mean (SD)
No Suicide attempts LT Mean (SD)
F
df
p
46.83 (14.49) 10.25 (3.38) 7.33 (3.33) 7.91 (3.17) 8.91 (3.80) 12.41 (5.85)
37.13 (10.71) 7.00 (3.47) 5.93 (2.32) 5.97 (2.74) 7.21 (2.35) 11.00 (5.36)
6.71 8.42 2.85 4.45 3.76 0.64
1 1 1 1 1 1
0.01 0.0053 0.09 0.03 0.057 0.42
46.85 (12.44) 12.35 (5.04) 7.57 (4.68) 6.28 (1.68) 6.64 (1.69) 14.00 (5.81)
38.28 (8.94) 7.34 (3.09) 5.93 (1.90) 5.75 (1.79) 7.03 (2.08) 12.21 (4.52)
7.01 17.13 2.87 0.89 0.37 1.26
1 1 1 1 1 1
0.01 0.0002 0.09 0.34 0.54 0.26
BD I ¼patients with bipolar disorder type I; BD II ¼ patients with bipolar disorder type II; HC ¼ healthy controls; LT ¼life time; SD ¼standard deviation; df¼ degrees of freedom.
experiences than HC. The trauma summary score and emotional abuse characterized both BD subtypes compared to HC. Furthermore, sexual abuse was more frequent in BD I, but not in BD II, than in HC, whereas emotional neglect was more frequent in BD II, but not in BD I, than in HC. It is noteworthy that when the two BD subtypes were compared, they showed no significant differences in any type of childhood trauma. This is not surprising, because BD I and BD II belong to the same clinical entity. Childhood trauma per se is only one of many possible pathogenetic factors (Etain et al., 2008) and it is not strong enough to distinguish the two BD subtypes. In any case, with respect to HC, BD subtypes have different sensitivity to various types of childhood trauma. As pointed out in the bipolar spectrum hypothesis (Akiskal, 1996; Phelps et al., 2008), this different sensitivity can be explained by considering that although BD patients have the same disease their clinical and psychopathological characteristics are very different (for a review see Vieta and Suppes, 2008). Sometimes these differences are just “nuances” that can be observed only when they are directly compared with a completely independent group, such as the HC group. This may be the case of the “sensitity to childhood trauma” dimension. The evidence that emotional abuse is particularly linked to BD (Etain et al., 2010) is consistent with our finding that childhood experiences of emotional abuse characterized patients with both types of BD. Furthermore, it could be connected to real dysfunctional attitudes of parents or to inadequate emotional responses of patients. Already in the early 19th Century, Minkowski highlighted that in manic-depressive illness “synchronism” with life experiences was excessive and inappropriate (Minkoswski, 1927). Today, the existence of hypersensitivity to emotional stimuli in patients with BD is known (M’bailara et al., 2009; Mathieu et al., 2014), even in states of euthymia (Henry et al., 2008). Moreover, there is evidence that affective lability in patients with BD is associated with greater severity of childhood trauma, specifically with emotional abuse and neglect (Aas et al., 2014). In our sample, childhood experiences of emotional neglect (and possibly emotional abuse) are more frequent in patients diagnosed with BD II than in HC. It is interesting to note that interpersonal sensitivity, a characteristic linked to childhood abuse, has already been described as an important feature of BD II (Akiskal and Benazzi, 2005; Benazzi and Rihmer, 2000). In the future, longitudinal investigations should focus on the primary/secondary grading of the childhood emotional abuse/interpersonal sensitivity relationship. Several studies reported a link between the severity of sexual abuse and psychosis (Houston et al., 2008; Janssen et al., 2004; Read et al., 2005). It is interesting to note that in our sample BD I patients, who were significantly more psychotic than BD II, had more sexual abuse experiences compared to HC. In an attempt to explain the relationship between psychosis and sexual abuse some authors have suggested that affective symptoms, basically depression and anxiety,
may primarily mediate this association (Bebbington et al., 2011). Thus, future studies could use BD as a model to understand how psychotic symptoms are associated with early traumatic events. The presence of childhood trauma may be associated with increased severity of some clinical characteristics, depending on the different subtypes (for a review see Daruy‐Filho et al., 2011). Previous studies have stressed the clinical relevance of the relationship between childhood trauma in BD patients, which is considered a homogeneous entity, and suicide attempts (Carballo et al., 2008; Leverich et al., 2003, 2002). Suicide attempts are also associated with both sexual and emotional abuse (Etain et al., 2013) or with only sexual abuse (Garno et al., 2005). Our results indicate that patients reporting lifetime suicide attempts obtained a higher childhood trauma summary score than patients who made no attempts. Moreover, this is the first study in which the two representative groups of patients with BD I and BD II have been considered separately. We also clarified how this distinction is relevant in analyzing the effect of childhood trauma on suicidality, indicating that emotional abuse is relevant to suicidality in both BD types, but sexual abuse only in BD I. Despite this difference, results indicate that there may be a direct relationship between childhood trauma and suicidality. In fact, according to the logistic regression analysis emotional abuse is strongly linked to lifetime suicide attempts, independently of whether BD I or BD II is diagnosed. This finding suggests the importance of adopting a dimensional approach towards suicidality in BD (Sani et al.,2011). Particularly, emotional abuse is a significant predictor of presence of life time suicide attempts in BD. It is important to note that in our study emotional abuse characterized both BD subtypes. Thus, it can be speculated that the high risk of suicide attempts, which characterized both BD subtypes, might be mediated by this relationship. Further longitudinal studies are needed to clarify this point. Before presenting our conclusions, we must acknowledge some issues that might limit the generalizability of our results. Indeed, the reliability of the retrospective assessment of childhood trauma experiences, as assessed with the CTQ during adulthood, may be influenced by uncontrolled recall bias. Nevertheless, the CTQ is currently used in clinical populations (Bernstein et al., 1994; Martinotti et al., 2009; Uçok and Bikmaz, 2007), especially in patients with affective disorders (Etain et al., 2010; Garno et al., 2005; Polanczyk et al., 2009), and it is indicated as one of the best instruments for evaluating childhood trauma (Daruy‐Filho et al., 2011). Further, the potential influence of illness duration or number of episodes on our results cannot be completely ruled out. We did not, however, find any significant relationship between severity of childhood trauma experiences and these clinical variables. Moreover, we did not assess the CTQ only in euthymic patients and we found a significant correlation between HAMD score and CTQ summary total score (r ¼ 0.24 p¼ 0.011) and
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between HAMA and CTQ summary total score (r ¼0.25 p ¼0.007). This could be due to either a real recall bias or to the fact that childhood trauma can worsen the depressive condition. Future longitudinal studies should investigate their causal relationship. Finally, we did not find a significant correlation between the CTQ trauma summary score and the YMRS for mania symptom severity or any significant relationship between severity of childhood trauma and mood states. Another limitation of our study is that the sample was rather small and that suicidality was assessed using a semistructured questionnaire, not a validated questionnaire. In conclusion, the results of our study indicate the importance of assessing childhood trauma in BD patients. Indeed, this is important for both clinical and research purposes. First, it can unveil slight differences between BD subtypes that are normally difficult to identify. This potentially different sensitivity in the CTQ subscores is evident only in comparison with the HC group; therefore, further studies on the relationship between BD and childhood trauma should always include a HC group. Second, the relationship between suicidality and CTQ has obvious clinical relevance. Therefore, all BD patients who have undergone emotional abuse and all BD I patients who have undergone sexual abuse should be treated with particular attention because of their possible suicide behavior. Our results show that the assessment of early trauma should definitely be included in the clinical evaluation of patients with bipolar disorders. Future studies with prospective longitudinal designs could extend our observations.
Role of funding source Nothing declared.
Conflict of interest No conflict declared.
Acknowledgment: We wish to thank Drs. Georgios D. Kotzalidis and Pietro De Rossi for providing useful cues that allowed us to improve the manuscript.
References Aas, M., Aminoff, S.R., Vik Lagerberg, T., Etain, B., Agartz, I., Andreassen, O.A, Melle, I., 2014. Affective lability in patients with bipolar disorders is associated with high levels of childhood trauma. Psychiatry Res. 218, 252–255. Akiskal, H.S., 1996. The prevalent clinical spectrum of bipolar disorders: beyond DSM-IV. J. Clin. Psychopharmacol. 16, 4S–14S. Akiskal, H.S., Benazzi, F., 2005. Atypical depression: A variant of bipolar II or a bridge between unipolar and bipolar II? J. Affect. Disord. 84, 209–217. American Psychiatric Association, 2000. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (DSM-IV-TR). American Psychiatric Association, Washington. Bebbington, P., Jonas, S., Kuipers, E., King, M., Cooper, C., Brugha, T., Meltzer, H., McManus, S., Jenkins, R., 2011. Childhood sexual abuse and psychosis: data from a cross-sectional national psychiatric survey in England. Br. J. Psychiatry 199, 29–37. Benazzi, F., Rihmer, Z., 2000. Sensitivity and specificity of DSM-IV atypical features for bipolar II disorder diagnosis. Psychiatry Res. 93, 257–262. Bernstein, D.P., Fink, L., Handelsman, L., Foote, J., Lovejoy, M., Wenzel, K., Sapareto, E., Ruggiero, J., 1994. Initial reliability and validity of a new retrospective measure of child abuse and neglect. Am. J. Psychiatry 151, 1132–1136. Bernstein, D.P., Stein, J.A., Newcomb, M.D., Walker, E., Pogge, D., Ahluvalia, T., Stokes, J., Handelsman, L., Medrano, M., Desmond, D., Zule, W., 2003. Development and validation of a brief screening version of the Childhood Trauma Questionnaire. Child Abus. Negl. 27, 169–190. Bücker, J., Muralidharan, K., Torres, I.J., Su, W., Kozicky, J., Silveira, L.E., Bond, D.J., Honer, W.G., Kauer-Sant’anna, M., Lam, R.W., Yatham, L.N., 2014. Childhood maltreatment and corpus callosum volume in recently diagnosed patients with bipolar I disorder: data from the Systematic Treatment Optimization Program for Early Mania (STOP-EM). J. Psychiatr. Res. 48, 65–72. Carballo, J.J., Harkavy-Friedman, J., Burke, A.K., Sher, L., Baca-Garcia, E., Sullivan, G.M., Grunebaum, M.F., Parsey, R.V., Mann, J.J., Oquendo, M.A., 2008. Family history of suicidal behavior and early traumatic experiences: additive effect on suicidality and course of bipolar illness? J. Affect. Disord. 109, 57–63.
Daruy‐Filho, L., Brietzke, E., Lafer, B., Grassi-Oliveira, R., 2011. Childhood maltreatment and clinical outcomes of bipolar disorder. Acta Psychiatr. Scand. 124, 427–434. Etain, B., Aas, M., Andreassen, O.A., Lorentzen, S., Dieset, I., Gard, S., Kahn, J.-P., Bellivier, F., Leboyer, M., Melle, I., Henry, C., 2013. Childhood trauma is associated with severe clinical characteristics of bipolar disorders. J. Clin. Psychiatry 74, 991–998. Etain, B., Mathieu, F., Henry, C., Raust, A., Roy, I., Germain, A., Leboyer, M., Bellivier, F., 2010. Preferential association between childhood emotional abuse and bipolar disorder. J. Trauma. Stress 23, 376–383. Etain, B., Henry, C., Bellivier, F., Mathieu, F., Leboyer, M., 2008. Beyond genetics: childhood affective trauma in bipolar disorder. Bipolar Disord. 10 (8), 867–876. First, M., Gibbon, M., Spitzer, R., Williams, J., Benjamin, L., 1997. Structured Clinical Interview for DSM-IV Axis II Personality Disorders, (SCID-II). American Psychiatric Association, Washington, D.C.. First, M., Spitzer, R., Gibbon, M., Williams, J., 2002a. Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition. (SCID-I/P). Biometrics Research, New York State Psychiatric Institute, New York. First, M., Spitzer, R., Gibbon, M., Williams, J., 2002b. Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Non-patient Edition. (SCID-I/ NP). Biometrics Research, New York State Psychiatric Institute, New York. Folstein, M.F., Folstein, S.E., McHugh, P.R., 1975. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 12, 189–198. Garno, J.L., Goldberg, J.F., Ramirez, P.M., Ritzler, B.A., 2005. Impact of childhood abuse on the clinical course of bipolar disorder. Br. J. Psychiatry 186, 121–125. Hamilton, M., 1959. The assessment of anxiety states by rating. Br. J. Med. Psychol. 32, 50–55. Hamilton, M., 1960. A rating scale for depression. J. Neurol. Neurosurg. Psychiatry 23, 56–62. Henry, C., van den Bulke, D., Bellivier, F., Roy, I., Swendsen, J., M’ Baïlara, K., Siever, L.J., Leboyer, M., 2008. Affective lability and affect intensity as core dimensions of bipolar disorders during euthymic period. Psychiatry Res. 159, 1–6. Houston, J.E., Murphy, J., Adamson, G., Stringer, M., Shevlin, M., 2008. Childhood sexual abuse, early cannabis use, and psychosis: testing an interaction model based on the national comorbidity survey. Schizophr. Bull. 34, 580–585. Iorio, M., Spalletta, G., Chiapponi, C., Luccichenti, G., Cacciari, C., 2013. White matter hyperintensities segmentation: a new semi-automated method. Front. Aging Neurosci. 5, 1–9. Janssen, I., Krabbendam, L., Back, M., Hanssen, M., Vollebergh, W., de Graaf, R., van Os, J., 2004. Childhood abuse as a risk factor for psychotic experiences. Acta Psychiatr. Scand. 109, 38–45. Kay, S.R., Fiszbein, A., Opler, L.A., 1987. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr. Bull. 13 (2), 261–276. Kraepelin, E., 1899. Psychiatrie. Ein Lehrbuch für Studirende und Aerzte. 6. Auflage. II. Band. Klinische Psychiatrie. IX. Das manisch-depressive Irresein. X. Die Verrücktheit (Paranoia). Verlag von Johann Ambrosius Barth, Leipzig, pp. 359–454. Leverich, G.S., Altshuler, L.L., Frye, M.A., Suppes, T., Keck, P.E., McElroy, S.L., Denicoff, K.D., Obrocea, G., Nolen, W.A., Kupka, R., Walden, J., Grunze, H., Perez, S., Luckenbaugh, D.A., Post, R.M., 2003. Factors associated with suicide attempts in 648 patients with bipolar disorder in the Stanley Foundation Bipolar Network. J. Clin. Psychiatry 64, 506–515. Leverich, G.S., McElroy, S.L., Suppes, T., Keck, P.E., Denicoff, K.D., Nolen, W.A., Altshuler, L.L., Rush, A.J., Kupka, R., Frye, M.A., Autio, K.A., Post, R.M., 2002. Early physical and sexual abuse associated with an adverse course of bipolar illness. Biol. Psychiatry 51, 288–297. M’bailara, K., Demotes-Mainard, J., Swendsen, J., Mathieu, F., Leboyer, M., Henry, C., 2009. Emotional hyper-reactivity in normothymic bipolar patients. Bipolar Disord. 11, 63–69. Martinotti, G., Carli, V., Tedeschi, D., Di Giannantonio, M., Roy, a., Janiri, L., Sarchiapone, M., 2009. Mono- and polysubstance dependent subjects differ on social factors, childhood trauma, personality, suicidal behavior, and comorbid Axis I diagnoses. Addict. Behav. 34, 790–793. Mathieu, F., Etain, B., Daban, C., Raymond, R., Raust, a., Cochet, B., Gard, S., M'Bailara, K., Desage, a., Kahn, J.P., Wajsbrot-Elgrabli, O., Cohen, R.F., Azorin, J.M., Leboyer, M., Bellivier, F., Scott, J., Henry, C., 2014. Affect intensity measure in bipolar disorders: a multidimensional approach. J. Affect. Disord. 157, 8–13. Measso, G., Cavarzeran, F., Zappalà, G., Lebowitz, B.D., Crook, T.H., Pirozzolo, F.J., Amaducci, L.A., Massari, D., Grigoletto, F., 1993. The mini‐mental state examination: normative study of an Italian random sample. Dev. Neuropsychol. Minkoswski, E., 1927. La schizophrénie: Psychopathologie des schizoïdes et des schizophrènes. Payot, Paris. Phelps, J., Angst, J., Katzow, J., Sadler, J., 2008. Validity and utility of bipolar spectrum models. Bipolar Disord. 10, 179–193. Polanczyk, G., Caspi, A., Williams, B., Price, T.S., Danese, A., Sugden, K., Uher, R., Poulton, R., Moffitt, T.E., 2009. Protective effect of CRHR1 gene variants on the development of adult depression following childhood maltreatment: replication and extension. Arch. Gen. Psychiatry 66, 978–985. Post, R.M., 1992. Transduction of psychosocial stress into the neurobiology of recurrent affective disorder. Am. J. Psychiatry 149, 999–1010. Read, J., van Os, J., Morrison, a P., Ross, C.A., 2005. Childhood trauma, psychosis and schizophrenia: a literature review with theoretical and clinical implications. Acta Psychiatr. Scand. 112, 330–350. Romero, S., Birmaher, B., Axelson, D., Goldstein, T., Goldstein, B.I., Gill, M.K., Iosif, A.M., Strober, M.A., Hunt, J., Esposito-Smythers, C., Ryan, N.D., Leonard, H., Keller, M.,
D. Janiri et al. / Journal of Affective Disorders 175 (2015) 92–97
2009. Prevalence and correlates of physical and sexual abuse in children and adolescents with bipolar disorder. J. Affect. Disord. 112, 144–150. Sani, G., Tondo, L., Koukopoulos, A., Reginaldi, D., Kotzalidis, G., Koukopoulos, A.E., Manfredi, G., Mazzarini, L., Pacchiarotti, I., Simonetti, A., Ambrosi, E., Angeletti, G., Girardi, P., Tatarelli, R., 2011. Suicide in a large population of former psychiatric inpatients. Psychiatry Clin. Neurosci. 65, 286–295. Scher, C.D., Stein, M.B., Asmundson, G.J.G., Mccreary, D.R., Forde, D.R., 2001. The Childhood Trauma Questionnaire in a community sample: psychometric properties and normative data. J. Trauma. Stress 14, 843–857.
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Uçok, A., Bikmaz, S., 2007. The effects of childhood trauma in patients with firstepisode schizophrenia. Acta Psychiatr. Scand. 116, 371–377. Vieta, E., Suppes, T., 2008. Bipolar II disorder: Arguments for and against a distinct diagnostic entity. Bipolar Disord. 10, 163–178. Watson, S., Gallagher, P., Dougall, D., Porter, R., Moncrieff, J., Ferrier, I.N., Young, A.H., 2013. Childhood trauma in bipolar disorder. Aust. N.Z. J. Psychiatry 48, 564–570. Young, R.C., Biggs, J.T., Ziegler, V.E., Meyer, D.A., 1978. A rating scale for mania: reliability, validity and sensitivity. Br. J. Psychiatry 133, 429–435.
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Journal of Affective Disorders journal homepage: www.elsevier.com/locate/jad
Research report
Childhood traumatic experiences of patients with bipolar disorder type I and type II Delfina Janiri a,b,c, Gabriele Sani a,b,c, Emanuela Danese a,b, Alessio Simonetti a,b,c, Elisa Ambrosi a,b, Gloria Angeletti a,b,c, Denise Erbuto b, Carlo Caltagirone a,d, Paolo Girardi a,b,c, Gianfranco Spalletta a,n a
IRCCS Santa Lucia Foundation, Neuropsychiatry Laboratory, Department of Clinical and Behavioral Neurology, Rome, Italy NESMOS Department (Neurosciences, Mental Health, and Sensory Organs), Sapienza University of Rome, School of Medicine and Psychology, Sant'Andrea Hospital, Rome, Italy c Centro Lucio Bini, Rome, Italy d Department of Medicine of Systems, Tor Vergata University of Rome, Italy b
art ic l e i nf o
a b s t r a c t
Article history: Received 10 August 2014 Received in revised form 20 December 2014 Accepted 24 December 2014 Available online 31 December 2014
Background: Childhood trauma is an important environmental stressor associated with bipolar disorders (BD). It is still not clear if it is differently distributed between BD I and BD II. Therefore, the aim of this research was to investigate the distribution patterns of childhood trauma in BD I and BD II. In this perspective, we also studied the relationship between childhood trauma and suicidality. Methods: We assessed 104 outpatients diagnosed with BD I (n ¼58) or BD II (n ¼46) according to DSMIV-TR criteria and 103 healthy controls (HC) matched for age, sex and education level. History of childhood trauma was obtained using the Childhood Trauma Questionnaire (CTQ). Results: All patients with BD had had more severe traumatic childhood experiences than HC. Both BD I and BD II patients differed significantly from HC for trauma summary score and emotional abuse. BD I patients differed significantly from HC for sexual abuse, and BD II differed from HC for emotional neglect. BD I and BD II did not significantly differ for any type of trauma. Suicide attempts were linked to both emotional and sexual abuse in BD I and only to emotional abuse in BD II. Emotional abuse was an independent predictor of lifetime suicide attempts in BD patients. Limitations: The reliability of the retrospective assessment of childhood trauma experiences with the CTQ during adulthood may be influenced by uncontrolled recall bias. Conclusions: The assessment of childhood trauma, which has great clinical importance because of its strong link with suicidality, can unveil slight differences between BD subtypes and HC. & 2014 Elsevier B.V. All rights reserved.
Keywords: Childhood trauma Bipolar disorders Suicide
1. Introduction Life events can significantly influence the clinical presentation of mood disorders (Kraepelin, 1899; Post, 1992). In particular, several studies consistently show that childhood trauma is a relevant environmental stressor associated with bipolar disorders (BD) (Bücker et al., 2014; Garno et al., 2005; Romero et al., 2009). Even though childhood trauma is more frequent in BD patients, considered as an homogeneous group, than in healthy control (HC) subjects (Etain et al., 2010; Watson et al., 2013), it is still not clear whether its occurrence is differently distributed in BD I and BD II. n Correspondence to: IRCCS Santa Lucia Foundation, Neuropsychiatry Laboratory, Department of Clinical and Behavioral Neurology,Via Ardeatina, 306 00179 Rome, Italy. Tel./fax: þ 0039 06 51501575. E-mail address: [email protected] (G. Spalletta).
http://dx.doi.org/10.1016/j.jad.2014.12.055 0165-0327/& 2014 Elsevier B.V. All rights reserved.
Childhood trauma can influence clinical outcome by inducing earlier disease onset, a greater number of episodes, a rapid cycling course and suicide attempts and increasing the need for hospitalization. Finally, specific types of childhood trauma are associated with different clinical features, (Daruy‐Filho et al., 2011) like suicide attempts (Carballo et al., 2008; Leverich et al., 2002). Specifically, previous studies found that suicide attempts are associated with both sexual and emotional abuse (Garno et al., 2005; Etain et al., 2013). In this study our main aim was to investigate how different types of childhood trauma are associated with the two subtypes of BD. We also investigated their influence on suicidality. We predicted that distinct types of childhood trauma would be associated with suicide attempts in different types of BD. We also investigated whether diagnosis of BD I or BD II subtypes modifies the relationship between childhood trauma and suicidality. We predicted that the effect of
D. Janiri et al. / Journal of Affective Disorders 175 (2015) 92–97
childhood trauma on suicidality might be more important than the categorical distinction between BD subtypes.
2. Materials and method 2.1. Participants We assessed 104 outpatients who had been diagnosed with BD I (n ¼58) and BD II (n ¼46) according to the DSM-IV-TR criteria (American Psychiatric Association., 2000) at the IRCCS Santa Lucia Foundation in Rome, Italy. All patients were initially recruited at two sites: Sant'Andrea Hospital and Santa Lucia Foundation in Rome. Subjects were screened for DSM-IV-TR Axis I disorders and clinical diagnoses were confirmed using the Structured Clinical Interview for DSM-IV-TR axis I Disorders, patient edition (SCID-I/P) (First et al., 2002a), conducted by trained raters. In addition to a diagnosis of BD, inclusion criteria were; (i) no additional axis I and II diagnoses evaluated by the structured interview SCID I/P and SCID-II (First et al., 1997); (ii) at least five years of education; (iii) no history of substance abuse during the last one year period evaluated by the structured interview SCID I/P. Exclusion criteria were: (i) traumatic head injury with loss of consciousness; (ii) lifetime history of major medical or neurological disorders; (iii) suspected cognitive impairment based on a Mini-Mental State Examination (MMSE) (Folstein et al., 1975) score lower than 24, consistent with normative data of the Italian population (Measso et al., 1993). (iv) non-Italian language native speaker; (v) any potential brain abnormality and microvascular lesion apparent on conventional FLAIR-scans. The presence, severity, and location of vascular lesions was computed using the semiautomated method recently published by our group (Iorio et al., 2013). All patients had been under stable pharmacological treatment for at least six months. We recruited 103 healthy controls (HC) from the same geographical area. All HC were screened for a current or lifetime history of DSM-IV-TR Axis I and II disorders using the SCID-I/NP (First et al., 2002b) and SCID-II (First et al., 1997). For the aims of this study, they were also interviewed to determine whether they had suicidal behavior; none reported lifetime suicidal behavior. They were also assessed to verify whether any first-degree relative was affected by mood disorders or schizophrenia. If they had a positive family history they were excluded. Exclusion criteria were the same as those for the patient group. The study was approved and undertaken in accordance with the guidelines of the Santa Lucia Foundation Ethics Committee and in accordance with the Principles of Human Rights, as adopted by the World Medical Association at the 18th WMA General Assembly, Helsinki, Finland, June 1964 and subsequently amended at the 64th WMA General Assembly, Fortaleza, Brazil, October 2013. All participants gave their written informed consent to participate in the research after they had received a complete explanation of the study procedures. 2.2. Clinical assessment We used the short form of the Childhood Trauma Questionnaire (CTQ) to measure adverse childhood events. This is a 28item, retrospective, self-report questionnaire (Bernstein et al., 2003) that investigates traumatic experiences in childhood; there are five possible answers, which range from “never true” to “very often true” depending on the frequency of the events. The questionnaire assesses five types of trauma: emotional abuse, emotional neglect, physical abuse, physical neglect and sexual abuse. For each type of trauma scores range from 5 to 25. A summary score (ranging from 25 to 125) is also calculated. Higher scores indicate greater childhood mistreatment. The CTQ has been
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used in both non-clinical (Scher et al., 2001) and clinical populations (Martinotti et al., 2009; Uçok and Bikmaz, 2007). It has a high degree of reliability (Bernstein et al., 1994) and it was also recently used to assess patients with affective disorders (Etain et al., 2010; Garno et al., 2005; Polanczyk et al., 2009). Psychopathology was rated using the Young Mania Rating Scale (YMRS) for mania symptom severity (Young et al., 1978), the 17-item Hamilton Rating Scale for Depression (HAMD) for depression symptom severity (Hamilton, 1960) and the Hamilton Rating Scale for Anxiety (HAMA) for anxiety symptom severity (Hamilton, 1959); all investigated the week prior to the assessment. All HC scored under the cut-off on the HAMD, YMRS and HAMA. Clinical characteristics were collected during a clinical interview. Psychotic features were evaluated with two items (i.e., item 1 “Delusions” and item 3 “Hallucinations”) of the Positive and Negative Symptoms scale (PANSS) (Kay et al., 1987), which are related to the moment of the evaluation and to the entire life. Suicidal ideation and suicidal attempts were assessed with a semistructured questionnaire consisting of two parts, one related to the past 6 months and the other to the lifetime (to the entire life). Each part included three questions: “Have you ever seriously thought about committing suicide?” “Have you ever made a plan for committing suicide?” “Have you ever attempted suicide?”. Respondents had to answer only “Yes” or “No”. Attempters then had to answer questions about their attempts: “How many time did you attempt suicide?” and “Can you briefly describe how you attempted suicide?”. From their responses to the last question we classified attempts as violent suicide attempts (defenestration, hanging, use of knives or fire arms) or non violent suicide attempts and as serious suicide attempts (requiring medical attention) or non serious suicide attempts.
2.3. Statistical analyses We compared the three groups' (i.e. BD I, BD II and HC) sociodemographic and clinical characteristics on the basis of the chisquare test for nominal variables and one-way analysis of variance (ANOVA) followed by post-hoc Scheffé tests for continuous variables and by pairwise post-hoc analyses for nominal variables. For the aims of this study, we focused on the distribution patterns of childhood trauma subtypes in BD I and BD II. First, we conducted a series of one-way ANOVAs, followed by Scheffé posthoc tests, to compare means among groups. The level of significance was set at p o0.05 for the ANOVA comparative measurements. To minimize the likelihood of type I errors, the ANOVAs were preceded by overall multivariate analysis of variance (MANOVA) using all of the continuous variables considered in each of the analyses as dependent variables. Second, we investigated the relationship between suicidality and childhood trauma subtypes by considering the previously found distribution patterns. Therefore, after having split our sample by diagnosis, we used a series of one-way ANOVAs to detect differences in means between groups of patients with a history of suicide attempts and patients without a history of suicide attempts, with the level of significance set at po 0.05. Prior to the ANOVAs, we carried MANOVAs using all the continuous variables considered in each of the analyses as dependent variables. To better identify the variables that significantly differentiated BD patients who had or had not made lifetime suicide attempts (considered as the dependent variable), a multivariate logistic regression model was used to estimate the odds of independent variables that differed significantly at a p o0.05 level. We included the BD and childhood trauma subtypes as independent variables to investigate whether the distinction between different BD diagnoses modifies the relationship between CTQ and suicidality.
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D. Janiri et al. / Journal of Affective Disorders 175 (2015) 92–97
Table 1 Sociodemographic and clinical characteristics of BD I, BD II and HC.
χ2
Characteristics
BP I (n¼ 58)
BP II (n¼ 46)
HC (n¼ 103)
F or
Age (years): mean 7(SD) Males: n (%) Educational Level (years): mean7 (SD) Duration of illness (years): mean 7(SD) Number of past episodes: mean 7 (SD) Number of past depressive episodes: mean 7 (SD) Presence of life time suicide attempts: n (%) Presence of life time psychotic symptoms: n (%) HAMD score: mean 7 (SD) YMRS score: mean 7 (SD) HAMA score: mean 7 (SD)
43.93 (13.55) 39 (67.24) 13.82 (3.42) 16.58 (13.06) 10.35 (12.57) 5.10 (5.97) 12 (20.69) 49 (84.48) 7.41 (5.89) 8.15 (9.28) 8.77 (6.88)
46.32 (13.69) 23 (50.00) 14.41 (3.32) 17.63 (12.27) 11.51 (10.07) 5.26 (4.40) 14 (30.43) 4 (8.69) 9.54 (6.63) 3.73 (3.48) 11.15 (6.58)
44.26 (15.68) 54 (52.42) 14.33 (3.52) – – –
0.40 4.18 0.49 0.17 0.19 0.02 1.29 58.96 2.99 9.35 3.17
– – – –
df
p
2 2 2 1 1 1 1 1 1 1 1
0.66 0.12 0.60 0.67 0.66 0.88 0.25 o .0001 0.08 0.0028 0.07
BD I ¼Patients with bipolar disorder type I; BD II ¼Patients with bipolar disorder type II; HC ¼ Healthy controls; SD ¼Standard deviation; df ¼Degrees of freedom; HAMD ¼Hamilton Depression Rating Scale; HAMA¼ Hamilton Anxiety Rating Scale; YMRS¼ Young Mania R Scale Table 2 Distribution patterns of childhood trauma subtypes in BD I and BD II.
Trauma summary score Emotional abuse Physical abuse Sexual abuse Emotional neglect Physical neglect
BD I Mean 7(SD)
BD II Mean 7 (SD)
HC Mean 7 (SD)
F#
df#
P#
HC vs BD I* (p)
HC vs BD II* (p)
BD I vs BD II* (p)
39.13 (12.12) 7.67 (3.67) 6.22 (2.59) 6.37 (2.91) 11.29 (5.44) 7.56 (2.76)
40.89 (10.75) 8.87 (4.40) 6.43 (3.06) 5.91 (1.76) 12.76 (4.95) 6.91 (1.96)
33.09 (7.34) 6.19 (2.10) 5.56 (1.43) 5.19 (0.81) 9.48 (4.49) 6.66 (3.64)
13.27 11.95 3.06 8.11 7.72 1.60
2 2 2 2 2 2
o 0.0001 o 0.0001 0.048 0.0004 0.0006 0.20
0.0009 0.02 0.19 0.0006 0.08 0.20
o 0.0001 o 0.0001 0.09 0.91 0.001 0.89
0.65 0.16 0.89 0.44 0.31 0.56
BD I¼ Patients with bipolar disorder type I; BD II ¼ Patients with bipolar disorder type II; HC ¼ Healthy controls; SD ¼ Standard deviation; df¼ Degrees of freedom. factorial ANOVA
#
n
Scheffé post hoc test
3. Results 3.1. Sociodemographic and clinical characteristics The three groups, i.e., BD I, BD II and HC, did not differ significantly for age, gender or educational level. At the time of clinical assessment patients with BD I obtained significantly higher YMRS scores than patients with BD II (see Table 1). Moreover, the two diagnostic subtypes did not differ for HAMD and HAMA. In the overall group of patients with a diagnosis of BD, 26 reported lifetime suicide attempts (BD I n ¼12, % ¼20.69; BD II n ¼14, % ¼30.43). The mean and the standard deviation (mean7 SD) for the number of suicide attempts in the BD I and the BD II group were 1.75 70.96 and 1.28 7 0.46. BD I and BD II did not significantly differ for the presence of lifetime suicide attempts (see Table 1). Moreover, the two BP subtypes did not differ for the number of suicide attempts. In the overall group of patients, 23 reported that their suicide attempts were serious (BD I n ¼11, % ¼ 91.66; BD II n ¼12, % ¼85.71) and 11 that they were violent (BD I n ¼7, %¼ 58.33; BD II n ¼4, % ¼28.57). BD I and BD II did not significantly differ for these characteristics. In the overall group of patients with a diagnosis of BD, 53 reported lifetime psychotic symptoms (BD I n¼49,%¼84.48; BD II n¼4, %¼ 8.69). Fifty two patients reported delusions (BD I n¼49, %¼ 84.48; BD II n¼3, %¼6.52) and 14 reported hallucinations (BD I: n¼12, %¼20.69; BD II: n¼ 2, %¼ 4.34). BD I differed significantly from BD II concerning the presence of lifetime psychotic symptoms (see Table 1) and for both delusions (χ2 ¼ 62.36; d.f.¼1; p¼ o.0001) and hallucinations (χ2 ¼ 5.88; d.f.¼1; p¼0.01).
experiences on BD diagnostic subtypes. Factorial ANOVAs indicated a main effect of diagnosis on all types of childhood trauma (see Table 2). In particular, a series of pairwise Scheffé post-hoc analyses clarified that both BD I and BD II differed significantly from HC regarding the trauma summary score and emotional abuse. Further, only BD I differed significantly from HC for sexual abuse and only BD II differed significantly from HC for emotional neglect. In all cases, patients with BD suffered more severe trauma experiences than HC (see Table 2). BD I and BD II patients did not significantly differ for any types of childhood trauma. 3.3. Relationship between childhood trauma and lifetime suicide attempts A preliminary MANOVA found a significant global effect (Wilk's Lambda ¼0.78, F¼5.49, df ¼5,98, p ¼0.0002) of childhood traumas on the presence of lifetime suicide attempts (categorized as YES/ NO). As shown Table 3, we found that: (i) the trauma summary score and emotional abuse were more severe in BD I and BD II patients with previous lifetime suicide attempts, and (ii) sexual abuse was more severe in BD I patients with previous lifetime suicide attempts. In the multivariate logistic regression only emotional abuse significantly predicted lifetime suicide attempts. Specifically, the odds (OR ¼ 1.31, 95%CI ¼1.10–1.57; p ¼0.0019) of belonging to the group of BD patients who attempted suicide explained 18.5% of the variance (R2) of the dependent variable.
4. Discussion 3.2. Distribution patterns of childhood trauma subtypes in BD I And BD II A preliminary MANOVA revealed a significant global effect (Wilks' Lambda¼0.82, F¼4.12, df¼ 10, p¼ o0.0001) of childhood trauma
This study was aimed at evaluating how different types of childhood trauma are associated with the two subtypes of BD disorder compared with HC. First, the results show that BD patients (divided into BD I and BD II) reported more childhood traumatic
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Table 3 Relationship between childhood trauma experiences and lifetime suicide attempts. BD I
Trauma summary score Emotional abuse Physical abuse Sexual abuse Physical Neglect Emotional neglect
BD II
Suicide attempts LT Mean (SD)
No Suicide attempts LT Mean (SD)
F
df
p
Suicide attempts LT Mean (SD)
No Suicide attempts LT Mean (SD)
F
df
p
46.83 (14.49) 10.25 (3.38) 7.33 (3.33) 7.91 (3.17) 8.91 (3.80) 12.41 (5.85)
37.13 (10.71) 7.00 (3.47) 5.93 (2.32) 5.97 (2.74) 7.21 (2.35) 11.00 (5.36)
6.71 8.42 2.85 4.45 3.76 0.64
1 1 1 1 1 1
0.01 0.0053 0.09 0.03 0.057 0.42
46.85 (12.44) 12.35 (5.04) 7.57 (4.68) 6.28 (1.68) 6.64 (1.69) 14.00 (5.81)
38.28 (8.94) 7.34 (3.09) 5.93 (1.90) 5.75 (1.79) 7.03 (2.08) 12.21 (4.52)
7.01 17.13 2.87 0.89 0.37 1.26
1 1 1 1 1 1
0.01 0.0002 0.09 0.34 0.54 0.26
BD I ¼patients with bipolar disorder type I; BD II ¼ patients with bipolar disorder type II; HC ¼ healthy controls; LT ¼life time; SD ¼standard deviation; df¼ degrees of freedom.
experiences than HC. The trauma summary score and emotional abuse characterized both BD subtypes compared to HC. Furthermore, sexual abuse was more frequent in BD I, but not in BD II, than in HC, whereas emotional neglect was more frequent in BD II, but not in BD I, than in HC. It is noteworthy that when the two BD subtypes were compared, they showed no significant differences in any type of childhood trauma. This is not surprising, because BD I and BD II belong to the same clinical entity. Childhood trauma per se is only one of many possible pathogenetic factors (Etain et al., 2008) and it is not strong enough to distinguish the two BD subtypes. In any case, with respect to HC, BD subtypes have different sensitivity to various types of childhood trauma. As pointed out in the bipolar spectrum hypothesis (Akiskal, 1996; Phelps et al., 2008), this different sensitivity can be explained by considering that although BD patients have the same disease their clinical and psychopathological characteristics are very different (for a review see Vieta and Suppes, 2008). Sometimes these differences are just “nuances” that can be observed only when they are directly compared with a completely independent group, such as the HC group. This may be the case of the “sensitity to childhood trauma” dimension. The evidence that emotional abuse is particularly linked to BD (Etain et al., 2010) is consistent with our finding that childhood experiences of emotional abuse characterized patients with both types of BD. Furthermore, it could be connected to real dysfunctional attitudes of parents or to inadequate emotional responses of patients. Already in the early 19th Century, Minkowski highlighted that in manic-depressive illness “synchronism” with life experiences was excessive and inappropriate (Minkoswski, 1927). Today, the existence of hypersensitivity to emotional stimuli in patients with BD is known (M’bailara et al., 2009; Mathieu et al., 2014), even in states of euthymia (Henry et al., 2008). Moreover, there is evidence that affective lability in patients with BD is associated with greater severity of childhood trauma, specifically with emotional abuse and neglect (Aas et al., 2014). In our sample, childhood experiences of emotional neglect (and possibly emotional abuse) are more frequent in patients diagnosed with BD II than in HC. It is interesting to note that interpersonal sensitivity, a characteristic linked to childhood abuse, has already been described as an important feature of BD II (Akiskal and Benazzi, 2005; Benazzi and Rihmer, 2000). In the future, longitudinal investigations should focus on the primary/secondary grading of the childhood emotional abuse/interpersonal sensitivity relationship. Several studies reported a link between the severity of sexual abuse and psychosis (Houston et al., 2008; Janssen et al., 2004; Read et al., 2005). It is interesting to note that in our sample BD I patients, who were significantly more psychotic than BD II, had more sexual abuse experiences compared to HC. In an attempt to explain the relationship between psychosis and sexual abuse some authors have suggested that affective symptoms, basically depression and anxiety,
may primarily mediate this association (Bebbington et al., 2011). Thus, future studies could use BD as a model to understand how psychotic symptoms are associated with early traumatic events. The presence of childhood trauma may be associated with increased severity of some clinical characteristics, depending on the different subtypes (for a review see Daruy‐Filho et al., 2011). Previous studies have stressed the clinical relevance of the relationship between childhood trauma in BD patients, which is considered a homogeneous entity, and suicide attempts (Carballo et al., 2008; Leverich et al., 2003, 2002). Suicide attempts are also associated with both sexual and emotional abuse (Etain et al., 2013) or with only sexual abuse (Garno et al., 2005). Our results indicate that patients reporting lifetime suicide attempts obtained a higher childhood trauma summary score than patients who made no attempts. Moreover, this is the first study in which the two representative groups of patients with BD I and BD II have been considered separately. We also clarified how this distinction is relevant in analyzing the effect of childhood trauma on suicidality, indicating that emotional abuse is relevant to suicidality in both BD types, but sexual abuse only in BD I. Despite this difference, results indicate that there may be a direct relationship between childhood trauma and suicidality. In fact, according to the logistic regression analysis emotional abuse is strongly linked to lifetime suicide attempts, independently of whether BD I or BD II is diagnosed. This finding suggests the importance of adopting a dimensional approach towards suicidality in BD (Sani et al.,2011). Particularly, emotional abuse is a significant predictor of presence of life time suicide attempts in BD. It is important to note that in our study emotional abuse characterized both BD subtypes. Thus, it can be speculated that the high risk of suicide attempts, which characterized both BD subtypes, might be mediated by this relationship. Further longitudinal studies are needed to clarify this point. Before presenting our conclusions, we must acknowledge some issues that might limit the generalizability of our results. Indeed, the reliability of the retrospective assessment of childhood trauma experiences, as assessed with the CTQ during adulthood, may be influenced by uncontrolled recall bias. Nevertheless, the CTQ is currently used in clinical populations (Bernstein et al., 1994; Martinotti et al., 2009; Uçok and Bikmaz, 2007), especially in patients with affective disorders (Etain et al., 2010; Garno et al., 2005; Polanczyk et al., 2009), and it is indicated as one of the best instruments for evaluating childhood trauma (Daruy‐Filho et al., 2011). Further, the potential influence of illness duration or number of episodes on our results cannot be completely ruled out. We did not, however, find any significant relationship between severity of childhood trauma experiences and these clinical variables. Moreover, we did not assess the CTQ only in euthymic patients and we found a significant correlation between HAMD score and CTQ summary total score (r ¼ 0.24 p¼ 0.011) and
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between HAMA and CTQ summary total score (r ¼0.25 p ¼0.007). This could be due to either a real recall bias or to the fact that childhood trauma can worsen the depressive condition. Future longitudinal studies should investigate their causal relationship. Finally, we did not find a significant correlation between the CTQ trauma summary score and the YMRS for mania symptom severity or any significant relationship between severity of childhood trauma and mood states. Another limitation of our study is that the sample was rather small and that suicidality was assessed using a semistructured questionnaire, not a validated questionnaire. In conclusion, the results of our study indicate the importance of assessing childhood trauma in BD patients. Indeed, this is important for both clinical and research purposes. First, it can unveil slight differences between BD subtypes that are normally difficult to identify. This potentially different sensitivity in the CTQ subscores is evident only in comparison with the HC group; therefore, further studies on the relationship between BD and childhood trauma should always include a HC group. Second, the relationship between suicidality and CTQ has obvious clinical relevance. Therefore, all BD patients who have undergone emotional abuse and all BD I patients who have undergone sexual abuse should be treated with particular attention because of their possible suicide behavior. Our results show that the assessment of early trauma should definitely be included in the clinical evaluation of patients with bipolar disorders. Future studies with prospective longitudinal designs could extend our observations.
Role of funding source Nothing declared.
Conflict of interest No conflict declared.
Acknowledgment: We wish to thank Drs. Georgios D. Kotzalidis and Pietro De Rossi for providing useful cues that allowed us to improve the manuscript.
References Aas, M., Aminoff, S.R., Vik Lagerberg, T., Etain, B., Agartz, I., Andreassen, O.A, Melle, I., 2014. Affective lability in patients with bipolar disorders is associated with high levels of childhood trauma. Psychiatry Res. 218, 252–255. Akiskal, H.S., 1996. The prevalent clinical spectrum of bipolar disorders: beyond DSM-IV. J. Clin. Psychopharmacol. 16, 4S–14S. Akiskal, H.S., Benazzi, F., 2005. Atypical depression: A variant of bipolar II or a bridge between unipolar and bipolar II? J. Affect. Disord. 84, 209–217. American Psychiatric Association, 2000. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (DSM-IV-TR). American Psychiatric Association, Washington. Bebbington, P., Jonas, S., Kuipers, E., King, M., Cooper, C., Brugha, T., Meltzer, H., McManus, S., Jenkins, R., 2011. Childhood sexual abuse and psychosis: data from a cross-sectional national psychiatric survey in England. Br. J. Psychiatry 199, 29–37. Benazzi, F., Rihmer, Z., 2000. Sensitivity and specificity of DSM-IV atypical features for bipolar II disorder diagnosis. Psychiatry Res. 93, 257–262. Bernstein, D.P., Fink, L., Handelsman, L., Foote, J., Lovejoy, M., Wenzel, K., Sapareto, E., Ruggiero, J., 1994. Initial reliability and validity of a new retrospective measure of child abuse and neglect. Am. J. Psychiatry 151, 1132–1136. Bernstein, D.P., Stein, J.A., Newcomb, M.D., Walker, E., Pogge, D., Ahluvalia, T., Stokes, J., Handelsman, L., Medrano, M., Desmond, D., Zule, W., 2003. Development and validation of a brief screening version of the Childhood Trauma Questionnaire. Child Abus. Negl. 27, 169–190. Bücker, J., Muralidharan, K., Torres, I.J., Su, W., Kozicky, J., Silveira, L.E., Bond, D.J., Honer, W.G., Kauer-Sant’anna, M., Lam, R.W., Yatham, L.N., 2014. Childhood maltreatment and corpus callosum volume in recently diagnosed patients with bipolar I disorder: data from the Systematic Treatment Optimization Program for Early Mania (STOP-EM). J. Psychiatr. Res. 48, 65–72. Carballo, J.J., Harkavy-Friedman, J., Burke, A.K., Sher, L., Baca-Garcia, E., Sullivan, G.M., Grunebaum, M.F., Parsey, R.V., Mann, J.J., Oquendo, M.A., 2008. Family history of suicidal behavior and early traumatic experiences: additive effect on suicidality and course of bipolar illness? J. Affect. Disord. 109, 57–63.
Daruy‐Filho, L., Brietzke, E., Lafer, B., Grassi-Oliveira, R., 2011. Childhood maltreatment and clinical outcomes of bipolar disorder. Acta Psychiatr. Scand. 124, 427–434. Etain, B., Aas, M., Andreassen, O.A., Lorentzen, S., Dieset, I., Gard, S., Kahn, J.-P., Bellivier, F., Leboyer, M., Melle, I., Henry, C., 2013. Childhood trauma is associated with severe clinical characteristics of bipolar disorders. J. Clin. Psychiatry 74, 991–998. Etain, B., Mathieu, F., Henry, C., Raust, A., Roy, I., Germain, A., Leboyer, M., Bellivier, F., 2010. Preferential association between childhood emotional abuse and bipolar disorder. J. Trauma. Stress 23, 376–383. Etain, B., Henry, C., Bellivier, F., Mathieu, F., Leboyer, M., 2008. Beyond genetics: childhood affective trauma in bipolar disorder. Bipolar Disord. 10 (8), 867–876. First, M., Gibbon, M., Spitzer, R., Williams, J., Benjamin, L., 1997. Structured Clinical Interview for DSM-IV Axis II Personality Disorders, (SCID-II). American Psychiatric Association, Washington, D.C.. First, M., Spitzer, R., Gibbon, M., Williams, J., 2002a. Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition. (SCID-I/P). Biometrics Research, New York State Psychiatric Institute, New York. First, M., Spitzer, R., Gibbon, M., Williams, J., 2002b. Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Non-patient Edition. (SCID-I/ NP). Biometrics Research, New York State Psychiatric Institute, New York. Folstein, M.F., Folstein, S.E., McHugh, P.R., 1975. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 12, 189–198. Garno, J.L., Goldberg, J.F., Ramirez, P.M., Ritzler, B.A., 2005. Impact of childhood abuse on the clinical course of bipolar disorder. Br. J. Psychiatry 186, 121–125. Hamilton, M., 1959. The assessment of anxiety states by rating. Br. J. Med. Psychol. 32, 50–55. Hamilton, M., 1960. A rating scale for depression. J. Neurol. Neurosurg. Psychiatry 23, 56–62. Henry, C., van den Bulke, D., Bellivier, F., Roy, I., Swendsen, J., M’ Baïlara, K., Siever, L.J., Leboyer, M., 2008. Affective lability and affect intensity as core dimensions of bipolar disorders during euthymic period. Psychiatry Res. 159, 1–6. Houston, J.E., Murphy, J., Adamson, G., Stringer, M., Shevlin, M., 2008. Childhood sexual abuse, early cannabis use, and psychosis: testing an interaction model based on the national comorbidity survey. Schizophr. Bull. 34, 580–585. Iorio, M., Spalletta, G., Chiapponi, C., Luccichenti, G., Cacciari, C., 2013. White matter hyperintensities segmentation: a new semi-automated method. Front. Aging Neurosci. 5, 1–9. Janssen, I., Krabbendam, L., Back, M., Hanssen, M., Vollebergh, W., de Graaf, R., van Os, J., 2004. Childhood abuse as a risk factor for psychotic experiences. Acta Psychiatr. Scand. 109, 38–45. Kay, S.R., Fiszbein, A., Opler, L.A., 1987. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr. Bull. 13 (2), 261–276. Kraepelin, E., 1899. Psychiatrie. Ein Lehrbuch für Studirende und Aerzte. 6. Auflage. II. Band. Klinische Psychiatrie. IX. Das manisch-depressive Irresein. X. Die Verrücktheit (Paranoia). Verlag von Johann Ambrosius Barth, Leipzig, pp. 359–454. Leverich, G.S., Altshuler, L.L., Frye, M.A., Suppes, T., Keck, P.E., McElroy, S.L., Denicoff, K.D., Obrocea, G., Nolen, W.A., Kupka, R., Walden, J., Grunze, H., Perez, S., Luckenbaugh, D.A., Post, R.M., 2003. Factors associated with suicide attempts in 648 patients with bipolar disorder in the Stanley Foundation Bipolar Network. J. Clin. Psychiatry 64, 506–515. Leverich, G.S., McElroy, S.L., Suppes, T., Keck, P.E., Denicoff, K.D., Nolen, W.A., Altshuler, L.L., Rush, A.J., Kupka, R., Frye, M.A., Autio, K.A., Post, R.M., 2002. Early physical and sexual abuse associated with an adverse course of bipolar illness. Biol. Psychiatry 51, 288–297. M’bailara, K., Demotes-Mainard, J., Swendsen, J., Mathieu, F., Leboyer, M., Henry, C., 2009. Emotional hyper-reactivity in normothymic bipolar patients. Bipolar Disord. 11, 63–69. Martinotti, G., Carli, V., Tedeschi, D., Di Giannantonio, M., Roy, a., Janiri, L., Sarchiapone, M., 2009. Mono- and polysubstance dependent subjects differ on social factors, childhood trauma, personality, suicidal behavior, and comorbid Axis I diagnoses. Addict. Behav. 34, 790–793. Mathieu, F., Etain, B., Daban, C., Raymond, R., Raust, a., Cochet, B., Gard, S., M'Bailara, K., Desage, a., Kahn, J.P., Wajsbrot-Elgrabli, O., Cohen, R.F., Azorin, J.M., Leboyer, M., Bellivier, F., Scott, J., Henry, C., 2014. Affect intensity measure in bipolar disorders: a multidimensional approach. J. Affect. Disord. 157, 8–13. Measso, G., Cavarzeran, F., Zappalà, G., Lebowitz, B.D., Crook, T.H., Pirozzolo, F.J., Amaducci, L.A., Massari, D., Grigoletto, F., 1993. The mini‐mental state examination: normative study of an Italian random sample. Dev. Neuropsychol. Minkoswski, E., 1927. La schizophrénie: Psychopathologie des schizoïdes et des schizophrènes. Payot, Paris. Phelps, J., Angst, J., Katzow, J., Sadler, J., 2008. Validity and utility of bipolar spectrum models. Bipolar Disord. 10, 179–193. Polanczyk, G., Caspi, A., Williams, B., Price, T.S., Danese, A., Sugden, K., Uher, R., Poulton, R., Moffitt, T.E., 2009. Protective effect of CRHR1 gene variants on the development of adult depression following childhood maltreatment: replication and extension. Arch. Gen. Psychiatry 66, 978–985. Post, R.M., 1992. Transduction of psychosocial stress into the neurobiology of recurrent affective disorder. Am. J. Psychiatry 149, 999–1010. Read, J., van Os, J., Morrison, a P., Ross, C.A., 2005. Childhood trauma, psychosis and schizophrenia: a literature review with theoretical and clinical implications. Acta Psychiatr. Scand. 112, 330–350. Romero, S., Birmaher, B., Axelson, D., Goldstein, T., Goldstein, B.I., Gill, M.K., Iosif, A.M., Strober, M.A., Hunt, J., Esposito-Smythers, C., Ryan, N.D., Leonard, H., Keller, M.,
D. Janiri et al. / Journal of Affective Disorders 175 (2015) 92–97
2009. Prevalence and correlates of physical and sexual abuse in children and adolescents with bipolar disorder. J. Affect. Disord. 112, 144–150. Sani, G., Tondo, L., Koukopoulos, A., Reginaldi, D., Kotzalidis, G., Koukopoulos, A.E., Manfredi, G., Mazzarini, L., Pacchiarotti, I., Simonetti, A., Ambrosi, E., Angeletti, G., Girardi, P., Tatarelli, R., 2011. Suicide in a large population of former psychiatric inpatients. Psychiatry Clin. Neurosci. 65, 286–295. Scher, C.D., Stein, M.B., Asmundson, G.J.G., Mccreary, D.R., Forde, D.R., 2001. The Childhood Trauma Questionnaire in a community sample: psychometric properties and normative data. J. Trauma. Stress 14, 843–857.
97
Uçok, A., Bikmaz, S., 2007. The effects of childhood trauma in patients with firstepisode schizophrenia. Acta Psychiatr. Scand. 116, 371–377. Vieta, E., Suppes, T., 2008. Bipolar II disorder: Arguments for and against a distinct diagnostic entity. Bipolar Disord. 10, 163–178. Watson, S., Gallagher, P., Dougall, D., Porter, R., Moncrieff, J., Ferrier, I.N., Young, A.H., 2013. Childhood trauma in bipolar disorder. Aust. N.Z. J. Psychiatry 48, 564–570. Young, R.C., Biggs, J.T., Ziegler, V.E., Meyer, D.A., 1978. A rating scale for mania: reliability, validity and sensitivity. Br. J. Psychiatry 133, 429–435.