Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎
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Brief report
Affective lability in patients with bipolar disorders is associated with high levels of childhood trauma Monica Aas a,b,n, Sofie R. Aminoff b,c, Trine Vik Lagerberg b, Bruno Etain d,e,f,g, Ingrid Agartz a,h, Ole A. Andreassen a,b,g, Ingrid Melle a,b a
NORMENT, Institute of Clinical Medicine, University of Oslo, Norway Psychosis Research Unit, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway c Department of Specialized Inpatient Treatment, Akershus University Hospital, Norway d AP-HP, Hôpital H. Mondor – A. Chenevier, Pôle de Psychiatry, Créteil 94000, France e Inserm, U955, Créteil 94000, France f Fondation Fondamental, Créteil, France g ENBREC, European Network of Bipolar Research Expert Centres (ENBREC), Paris, France h Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway b
art ic l e i nf o
a b s t r a c t
Article history: Received 2 September 2013 Received in revised form 25 March 2014 Accepted 28 March 2014
This study aimed to investigate associations between a history of childhood trauma and levels of affective lability in bipolar patients compared to controls. Forty-two patients and 14 controls were assessed using the Affective Lability Scale (ALS) and the Childhood Trauma Questionnaire (CTQ). Affective Lability Score was significantly associated with scores on the Childhood Trauma Questionnaire. A multivariate regression model indicated a relationship between childhood trauma scores and differences in affective lability between patients and controls. & 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Childhood Trauma Questionnaire (CTQ) Affective Lability Scale (ALS) Bipolar disorders
1. Introduction Affective lability is a core feature of several mental disorders, including bipolar disorders (Goodman et al., 2003; Aminoff et al., 2012). Affective lability is defined as frequent and intense fluctuations in affect in response to both pleasant and unpleasant events, and can be measured with the Affective Lability Scale (ALS). Studies of bipolar disorders suggest heightened affective lability and intensity both in manic and mixed episodes (Henry et al., 2003), as well as trait affective lability in euthymic states (Henry et al., 2008). Previous research has linked childhood trauma, and specifically emotional abuse, to later affective lability in personality disorders (Goodman et al., 2003). Regarding bipolar disorders, one large study (n ¼202) showed that childhood trauma is associated with higher scores on the ALS, with the strongest association for emotional abuse (Etain et al., 2008). Childhood trauma has been linked to increased amygdala activation (van Harmelen et al., n Corresponding author at: NORMENT, KG Jebsen Psychosis Research Centre, TOP study group, Division of Mental Health and Addiction, Institute of Clinical Medicine, Bygg 49, Ullevål sykehus, PO Box 4956, Nydalen, 0424 Oslo, Norway. E-mail address: [email protected] (M. Aas).
2013), a brain region important for fear and emotions (Gallagher and Chiba, 1996; Aas et al., 2012b), supporting a relationship of childhood trauma with possible changes in emotional regulation. Childhood trauma has also been linked to changes in the prefrontal cortex that possibly affects the control of the emotiondriven impulses (Marquez et al., 2013). Thus childhood trauma may be related to changes in emotional regulation by increased emotional stimuli from the amygdala (particularly negative stimuli), combined with reduced control of these emotions by the prefrontal cortex. Several studies have found that severe mental disorders, such as bipolar disorders, are characterized by an increased level of reports of childhood trauma experiences compared to the general population (Etain et al., 2013; Aas et al., 2013). In bipolar disorders an increased level of childhood trauma is also associated with a more rapid cycling course, suicide attempts, more mood episodes and earlier age at onset (Daruy-Filho et al., 2011; Etain et al., 2008, 2012, 2013). This study is the first to investigate if childhood trauma, as measured by the Childhood Trauma Questionnaire (CTQ), mediates higher levels of Affective Liability Scores (ALS) in patients with bipolar disorders compared to controls. This is important for the further understanding of the mechanisms behind bipolar
http://dx.doi.org/10.1016/j.psychres.2014.03.046 0165-1781/& 2014 Elsevier Ireland Ltd. All rights reserved.
Please cite this article as: Aas, M., et al., Affective lability in patients with bipolar disorders is associated with high levels of childhood trauma. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.03.046i
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disorders that will hopefully also contribute to patients' treatment in the long-term. Based on our relatively small sample size with the limitations that follows, we aim to investigate the above in this brief report, which should be investigated further in a larger independent sample. Our hypotheses are as follows: (1) Patients will have significantly higher scores on the ALS and the CTQ compared to controls; (2) the total score on the ALS will be positively correlated with the total score on the CTQ, with the strongest correlation for emotional abuse; (3) childhood trauma will be associated with higher ALS scores in patients compared to controls.
2. Methods 2.1. Participants Participants were recruited consecutively from psychiatric units (outpatient and inpatient) in four major hospitals in Oslo as part of the larger Thematically Organized Psychosis (TOP) Research study. For the present study, 42 DSM-IVdiagnosed patients were recruited between 2007 and spring 2013, all of whom had a diagnosis of bipolar disorders (37 bipolar I disorder, two bipolar NOS, and three bipolar II); patients' age mean 7 S.D. was 30.8 7 10.6; 55% of the same were females. Twenty nine (64%) of the patients had experienced at least one psychotic episode. 14 persons without severe mental disorders or ongoing illicit drug abuse were recruited from the same geographical areas as healthy control subjects (Controls' age mean 7S.D.: 29.4 7 7.6; 37% females). This is an ongoing study, and the collection of CTQ from control subjects started later than the collection of CTQ from patients, explaining the larger N in patients compared to controls. Exclusion criteria for all groups were an unstable or uncontrolled medical condition that interferes with brain function, and age outside the range of 18–65 years. It is an ongoing debate whether borderline personality disorder (BPD) belongs to the bipolar spectrum (Coulston et al., 2012). In our study, however, we only included patients who met DSM-IV SCID 1 diagnostic criteria for bipolar disorder, independent of any possible personality disorders they may also have had. Moreover, controls did not have any current axis one disorders. The Regional Committee for Medical Research Ethics, and the Norwegian Data Inspectorate approved the study. All participants gave written informed consent. 2.2. Clinical assessment Clinical assessment was carried out by trained psychiatrists and clinical psychologists. Diagnosis was based on the Structured Clinical Interview for DSMIV Axis I disorders (SCID-I). Diagnostic reliability was found to be satisfactory (Ringen et al., 2008) with overall agreement for DSM-IV diagnostic categories of 82% and the overall κ 0.77 (95% CI: 0.60–0.94). Current positive and negative symptoms were rated using the Positive and Negative Syndrome Scale (PANSS) (Kay et al. 1987). Inter-rater reliability was acceptable with intra-class correlation coefficients (Shrout and Fleiss, 1979) for PANSS subscales ranging from 0.71 to 0.73. Participants were defined as currently psychotic if they scored 4 or higher on any one of the following PANSS items: P1, P3, P5, P6, and G9. Use of medication at the time of testing was determined through clinical interview and medical charts. In the patient group, 29 patients (69%) used one or more antipsychotics; 13 patients (31%) used anti-depressants, and 20 patients (48%) used at least one type of mood stabilizers. 2.3. Affective Lability Scale (ALS) Affective lability was measured using the Norwegian version of the Affective Lability Scale (ALS) (Harvey et al., 1989). The ALS includes 54 questions, rated from 0 to 3, and is divided into six sections that examine affective variations between euthymia on the one hand, and depression, elation, anger and anxiety on the other, and that also examine the affective variations between anxiety and depression, and between depression and elation. The total score is the sum of the question's scores divided by 54, thus ranging from 0 to 3, a score closer to 3 indicating greater affective lability.
with five items rated on a five-point Likert scale from 1 (never true) to 5 (very often true).
2.5. Statistical analyses Data were analyzed using the Predictive Analytic software (PASW), Version 18 (formerly SPSS Statistics). Continuous variables were presented as mean 7 standard deviation. As ALS and CTQ were not normally distributed we used non-parametric tests (Spearman's correlation and Mann–Whitney test), when comparing patients and controls on these clinical measures. For the mediation analysis, ALS and CTQ were log transformed before entered into the parametric logistic regression analysis. We also applied the principles for mediation analysis by Baron and Kenny (Baron and Kenny, 1986). As the dependent variable was dichotomous (patients versus controls), logistic regression was performed and Nagelkerke r2 was used to indicate the power of explanation of the model (Nagelkerke, 1991). Lastly, to avoid type 1 error, we corrected for number of childhood sub-groups (physical, sexual and emotional abuse, as well as physical and emotional neglect), using a significance level of 0.01 compared to a standard level of r 0.05. As this was a hypothesis driven study, with a priori ideas on directions, we decided this was sufficient without the potential of losing important data.
3. Results The patient group had a significantly higher CTQ total score compared to the control group (40.44 712.50 versus 29.75 74.29; Mann–Whitney test: z ¼ 2.85, p ¼0.004). Patients also had a significantly higher ALS total score compared to controls (1.01 70.72 versus 0.287 0.33; Mann–Whitney test: z¼ 3.75, p o0.001). Independent sample t-test was conducted comparing ALS scores in patients taking medication (anti-psychotic medication, antidepressants, or mood stabilizers), to patients not taking medication; no significant difference in ALS scores were observed between the groups (f¼ 0.001, t¼0.72, d.f.¼39, p¼0.47). In the patient group, ALS was significantly and positively correlated (Spearman's correlation, [rho]) with CTQ total score (r ¼0.40, p ¼0.009). Moreover, the most significant correlations were observed for emotional abuse (r ¼0.41, p ¼0.007), and emotional neglect (r ¼0.39, p¼ 0.01). No significant associations were shown in the control group only (r o 0.26; p 40.10). Lastly, logistic regression showed that ALS (entered as an independent variable) was significantly associated with the participant group (patients/ control; [Nagelkerke r2 ¼0.36, d.f. ¼1, p ¼0.004]). When both CTQ total score and ALS total score were added into the model as independent variables in the same multivariate regression
Table 1 Correlation between Affective Liability Scale (ALS) total score and childhood trauma. N
Affective Lability Scale (ALS) total score
Patients Physical abuse Sexual abuse Emotional abuse Emotional neglect Physical neglect
42 42 42 42 42
r ¼ 0.33; p¼ 0.035 r ¼ 0.33; p¼ 0.030 r ¼ 0.41; p¼ 0.007n r ¼ 0.39; p ¼0.01n r ¼ 0.18; p ¼0.27
Controls Physical abuse Sexual abuse Emotional abuse Emotional neglect Physical neglect
14 14 14 13 13
r o 0.01; p4 0.9 r ¼ 0.07; p¼ 0.81 r ¼ 0.09; p ¼0.75 r ¼ 0.17; p¼ 0.59 r ¼ 0.26; p ¼0.39
2.4. Childhood Trauma Questionnaire (CTQ) Traumatic events in childhood were rated using a Norwegian version of the Childhood Trauma Questionnaire (CTQ) (Bernstein et al., 2003; Aas et al., 2012a). This is a self-report questionnaire with 28-items (Bernstein et al., 2003), yielding scores on the following five subscales: trauma, emotional abuse, physical abuse, sexual abuse, physical neglect, and emotional neglect. Each subscale is measured
Spearman's correlation (rho); childhood trauma was based on the Childhood Trauma Questionnaire (CTQ) with data divided into sub-groups of scores ranging from 5 to 25; Affective Liability Scale (ALS) total score was based on 54 sub-items from the Affective Liability Scale added together (score ranging from 0 to 143/54); p values: bold ¼ pr 0.05. n
Significant after correction for multiple testing.
Please cite this article as: Aas, M., et al., Affective lability in patients with bipolar disorders is associated with high levels of childhood trauma. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.03.046i
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4.1. Limitations Although there were no significant correlations between medication and ALS scores, we cannot rule out that medication may have influenced our patients' scores on the ALS. Data on childhood trauma were obtained retrospectively with the inherent weakness of retrospective designs. However, the retrospective collection of childhood trauma in patients with severe mental disorders has been found to be a valid and reliable source in obtaining information in previous studies (Fisher et al., 2011). Also our relatively small sample size (patients, n¼ 42; controls, n ¼14) should be taken into consideration, and larger studies should be conducted to further investigate the relationship between childhood trauma, affective lability, and other clinical characteristics of bipolar disorders. Future studies should also investigate pathophysiological mechanisms underlying affective lability in bipolar disorder and the role of childhood trauma.
Role of funding source
Fig. 1. Affective Lability Score (ALS) and CTQ total score. Spearman's correlation: r ¼0.40, p ¼ 0.009. CTQ ¼ Childhood Trauma Questionnaire.
analysis, the model improved (Nagelkerke r2 ¼0.41), and the association level between ALS and subject group dropped (d. f. ¼1, p ¼0.04). The above indicates a relationship between childhood trauma scores and differences in affective lability scores between patients and controls (Table 1, Fig. 1). Seven of the patients presented current psychotic symptoms from the PANSS. Reassuringly when follow-up analysis was conducted excluding patients with a current psychotic episode, the relationship between childhood trauma and ALS score remained, indicating that our findings above were independent of current psychotic symptomatology. Moreover, our results remained the same also when excluding cases with current depressive symptoms (4 Z on PANSS).
4. Discussion Our data demonstrate significant positive associations between scores on the Affective Lability Scale (ALS) and childhood trauma, as measured by the Childhood Trauma Questionnaire (CTQ). This was shown particularly in patients with bipolar disorders with the strongest associations for emotional abuse, followed by emotional neglect. Further, the multivariate regression model indicated a relationship between childhood trauma scores and differences in affective lability scores between patients and controls. Our findings replicate previous studies showing an association between mood instability as measured by the ALS and reports of childhood trauma (Etain et al., 2008; Goodman et al., 2003), with the strongest association for emotional abuse. We have previously shown in a large sample of bipolar patients (n ¼587) that childhood trauma, and specifically emotional abuse, is associated with clinical expression in bipolar disorders, such as rapid cycling course, lifetime history of at least on suicide attempt, as well as number of mood episodes (Etain et al. 2013). Based upon emotional instability being associated with suicide attempts (PalmierClaus et al., 2012), as well as the relationship between rapid cycling and emotional instability (MacKinnon and Pies, 2006), further studies should investigate the relationship between affective lability, childhood trauma and other clinical expressions of bipolar disorders. This should be investigated in larger, and ideally prospective, studies.
This study was funded by grants from the Eastern Norway Health Authority (#2004123, #2006258) and the Research Council of Norway (#167153/V50).
Conflict of interest statement The authors declare that they have no conflict of interest concerning this manuscript.
Acknowledgments We thank the patients who took part in the study and the TOP study researchers who contributed to the data collection. Reference Aas, M., Djurovic, S., Athanasiu, L., Steen, N.E., Agartz, I., Lorentzen, S., Sundet, K., Andreassen, O.A., Melle, I., 2012a. Serotonin transporter gene polymorphism, childhood trauma, and cognition in patients with psychotic disorders. Schizophrenia Bulletin 38, 15–22. Aas, M., Etain, B., Bellivier, F., Henry, C., Lagerberg, T., Ringen, A., Agartz, I., Gard, S., Kahn, J.P., Leboyer, M., Andreassen, O.A., Melle, I., 2013. Additive effects of childhood abuse and cannabis abuse on clinical expressions of bipolar disorders. Psychological Medicine, 1–10. Aas, M., Navari, S., Gibbs, A., Mondelli, V., Fisher, H.L., Morgan, C., Morgan, K., Maccabe, J., Reichenberg, A., Zanelli, J., Fearon, P., Jones, P.B., Murray, R.M., Pariante, C.M., Dazzan, P., 2012b. Is there a link between childhood trauma, cognition, and amygdala and hippocampus volume in first-episode psychosis? Schizophrenia Research 137, 73–79. Aminoff, S.R., Jensen, J., Lagerberg, T.V., Hellvin, T., Sundet, K., Andreassen, O.A., Melle, I., 2012. An association between affective lability and executive functioning in bipolar disorder. Psychiatry Research 198, 58–61. Baron, R.M., Kenny, D.A., 1986. The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. Journal of Personality and Social Psychology 51, 1173–1182. 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 Abuse and Neglect 27, 169–190. Coulston, C.M., Tanious, M., Mulder, R.T., Porter, R.J., Malhi, G.S., 2012. Bordering on bipolar: the overlap between borderline personality and bipolarity. Australian and New Zealand Journal of Psychiatry 46, 506–521. Daruy-Filho, L., Brietzke, E., Lafer, B., Grassi-Oliveira, R., 2011. Childhood maltreatment and clinical outcomes of bipolar disorder. Acta Psychiatrica Scandinavica 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. Journal of Clinical Psychiatry 74, 991–998. Etain, B., Henry, C., Bellivier, F., Mathieu, F., Leboyer, M., 2008. Beyond genetics: childhood affective trauma in bipolar disorder. Bipolar Disorder 10, 867–876.
Please cite this article as: Aas, M., et al., Affective lability in patients with bipolar disorders is associated with high levels of childhood trauma. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.03.046i
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Etain, B., Mathieu, F., Liquet, S., Raust, A., Cochet, B., Richard, J.R., Gard, S., Zanouy, L., Kahn, J.P., Cohen, R.F., Bougerol, T., Henry, C., Leboyer, M., Bellivier, F., 2012. Clinical features associated with trait-impulsiveness in euthymic bipolar disorder patients. Journal of Affective Disorders 144, 240–247. Fisher, H.L., Craig, T.K., Fearon, P., Morgan, K., Dazzan, P., Lappin, J., Hutchinson, G., Doody, G.A., Jones, P.B., McGuffin, P., Murray, R.M., Leff, J., Morgan, C., 2011. Reliability and comparability of psychosis patients' retrospective reports of childhood abuse. Schizophrenia Bulletin 37, 546–553. Gallagher, M., Chiba, A.A., 1996. The amygdala and emotion. Current Opinion in Neurobiology 6, 221–227. Goodman, M., Weiss, D.S., Koenigsberg, H., Kotlyarevsky, V., New, A.S., Mitropoulou, V., Silverman, J.M., O'Flynn, K., Siever, L.J., 2003. The role of childhood trauma in differences in affective instability in those with personality disorders. CNS Spectrums 8, 763–770. Harvey, P.D., Greenberg, B.R., Serper, M.R., 1989. The affective lability scales: development, reliability, and validity. Journal of Clinical Psychology 45, 786–793. Henry, C., Swendsen, J., Van den Bulke, D., Sorbara, F., Demotes-Mainard, J., Leboyer, M., 2003. Emotional hyper-reactivity as a fundamental mood characteristic of manic and mixed states. European Psychiatry 18, 124–128. Henry, C., Van den Bulke, D., Bellivier, F., Roy, I., Swendsen, J., M'Bailara, K., Siever, L.J., Leboyer, M., 2008. Affective lability and affect intensity as core dimensions of bipolar disorders during euthymic period. Psychiatry Research 159, 1–6. Kay, S.R., Fiszbein, A., Opler, L.A., 1987. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261–276.
Marquez, C., Poirier, G.L., Cordero, M.I., Larsen, M.H., Groner, A., Marquis, J., Magistretti, P.J., Trono, D., Sandi, C., 2013. Peripuberty stress leads to abnormal aggression, altered amygdala and orbitofrontal reactivity and increased prefrontal MAOA gene expression. Transl. Psychiatry 3, e216. MacKinnon, D.F., Pies, R., 2006. Affective instability as rapid cycling: theoretical and clinical implications for borderline personality and bipolar spectrum disorders. Bipolar Disorder 8, 1–14. Nagelkerke, N.J.D., 1991. A note on a general definition of the coefficient of determination. Biometrika. Palmier-Claus, J.E., Taylor, P.J., Varese, F., Pratt, D., 2012. Does unstable mood increase risk of suicide? Theory, research and practice. Journal of Affective Disorders 143, 5–15. Ringen, P.A., Lagerberg, T.V., Birkenaes, A.B., Engen, J., Faerden, A., Jonsdottir, H., Nesvag, R., Friis, S., Opjordsmoen, S., Larsen, F., Melle, I., Andreassen, O.A., 2008. Differences in prevalence and patterns of substance use in schizophrenia and bipolar disorder. Psychological Medicine 38, 1241–1249. Shrout, P.E., Fleiss, J.L., 1979. Intraclass correlations: uses in assessing rater reliability. Schizophrenia Bulletin 86, 420–428. van Harmelen, A.L., van Tol, M.J., Demenescu, L.R., van der Wee, N.J., Veltman, D.J., Aleman, A., van Buchem, M.A., Spinhoven, P., Penninx, B.W., Elzinga, B.M., 2013. Enhanced amygdala reactivity to emotional faces in adults reporting childhood emotional maltreatment. Social Cognitive and Affective Neuroscience 8, 362–369.
Please cite this article as: Aas, M., et al., Affective lability in patients with bipolar disorders is associated with high levels of childhood trauma. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.03.046i
Contents lists available at ScienceDirect
Psychiatry Research journal homepage: www.elsevier.com/locate/psychres
Brief report
Affective lability in patients with bipolar disorders is associated with high levels of childhood trauma Monica Aas a,b,n, Sofie R. Aminoff b,c, Trine Vik Lagerberg b, Bruno Etain d,e,f,g, Ingrid Agartz a,h, Ole A. Andreassen a,b,g, Ingrid Melle a,b a
NORMENT, Institute of Clinical Medicine, University of Oslo, Norway Psychosis Research Unit, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway c Department of Specialized Inpatient Treatment, Akershus University Hospital, Norway d AP-HP, Hôpital H. Mondor – A. Chenevier, Pôle de Psychiatry, Créteil 94000, France e Inserm, U955, Créteil 94000, France f Fondation Fondamental, Créteil, France g ENBREC, European Network of Bipolar Research Expert Centres (ENBREC), Paris, France h Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway b
art ic l e i nf o
a b s t r a c t
Article history: Received 2 September 2013 Received in revised form 25 March 2014 Accepted 28 March 2014
This study aimed to investigate associations between a history of childhood trauma and levels of affective lability in bipolar patients compared to controls. Forty-two patients and 14 controls were assessed using the Affective Lability Scale (ALS) and the Childhood Trauma Questionnaire (CTQ). Affective Lability Score was significantly associated with scores on the Childhood Trauma Questionnaire. A multivariate regression model indicated a relationship between childhood trauma scores and differences in affective lability between patients and controls. & 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Childhood Trauma Questionnaire (CTQ) Affective Lability Scale (ALS) Bipolar disorders
1. Introduction Affective lability is a core feature of several mental disorders, including bipolar disorders (Goodman et al., 2003; Aminoff et al., 2012). Affective lability is defined as frequent and intense fluctuations in affect in response to both pleasant and unpleasant events, and can be measured with the Affective Lability Scale (ALS). Studies of bipolar disorders suggest heightened affective lability and intensity both in manic and mixed episodes (Henry et al., 2003), as well as trait affective lability in euthymic states (Henry et al., 2008). Previous research has linked childhood trauma, and specifically emotional abuse, to later affective lability in personality disorders (Goodman et al., 2003). Regarding bipolar disorders, one large study (n ¼202) showed that childhood trauma is associated with higher scores on the ALS, with the strongest association for emotional abuse (Etain et al., 2008). Childhood trauma has been linked to increased amygdala activation (van Harmelen et al., n Corresponding author at: NORMENT, KG Jebsen Psychosis Research Centre, TOP study group, Division of Mental Health and Addiction, Institute of Clinical Medicine, Bygg 49, Ullevål sykehus, PO Box 4956, Nydalen, 0424 Oslo, Norway. E-mail address: [email protected] (M. Aas).
2013), a brain region important for fear and emotions (Gallagher and Chiba, 1996; Aas et al., 2012b), supporting a relationship of childhood trauma with possible changes in emotional regulation. Childhood trauma has also been linked to changes in the prefrontal cortex that possibly affects the control of the emotiondriven impulses (Marquez et al., 2013). Thus childhood trauma may be related to changes in emotional regulation by increased emotional stimuli from the amygdala (particularly negative stimuli), combined with reduced control of these emotions by the prefrontal cortex. Several studies have found that severe mental disorders, such as bipolar disorders, are characterized by an increased level of reports of childhood trauma experiences compared to the general population (Etain et al., 2013; Aas et al., 2013). In bipolar disorders an increased level of childhood trauma is also associated with a more rapid cycling course, suicide attempts, more mood episodes and earlier age at onset (Daruy-Filho et al., 2011; Etain et al., 2008, 2012, 2013). This study is the first to investigate if childhood trauma, as measured by the Childhood Trauma Questionnaire (CTQ), mediates higher levels of Affective Liability Scores (ALS) in patients with bipolar disorders compared to controls. This is important for the further understanding of the mechanisms behind bipolar
http://dx.doi.org/10.1016/j.psychres.2014.03.046 0165-1781/& 2014 Elsevier Ireland Ltd. All rights reserved.
Please cite this article as: Aas, M., et al., Affective lability in patients with bipolar disorders is associated with high levels of childhood trauma. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.03.046i
M. Aas et al. / Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎
2
disorders that will hopefully also contribute to patients' treatment in the long-term. Based on our relatively small sample size with the limitations that follows, we aim to investigate the above in this brief report, which should be investigated further in a larger independent sample. Our hypotheses are as follows: (1) Patients will have significantly higher scores on the ALS and the CTQ compared to controls; (2) the total score on the ALS will be positively correlated with the total score on the CTQ, with the strongest correlation for emotional abuse; (3) childhood trauma will be associated with higher ALS scores in patients compared to controls.
2. Methods 2.1. Participants Participants were recruited consecutively from psychiatric units (outpatient and inpatient) in four major hospitals in Oslo as part of the larger Thematically Organized Psychosis (TOP) Research study. For the present study, 42 DSM-IVdiagnosed patients were recruited between 2007 and spring 2013, all of whom had a diagnosis of bipolar disorders (37 bipolar I disorder, two bipolar NOS, and three bipolar II); patients' age mean 7 S.D. was 30.8 7 10.6; 55% of the same were females. Twenty nine (64%) of the patients had experienced at least one psychotic episode. 14 persons without severe mental disorders or ongoing illicit drug abuse were recruited from the same geographical areas as healthy control subjects (Controls' age mean 7S.D.: 29.4 7 7.6; 37% females). This is an ongoing study, and the collection of CTQ from control subjects started later than the collection of CTQ from patients, explaining the larger N in patients compared to controls. Exclusion criteria for all groups were an unstable or uncontrolled medical condition that interferes with brain function, and age outside the range of 18–65 years. It is an ongoing debate whether borderline personality disorder (BPD) belongs to the bipolar spectrum (Coulston et al., 2012). In our study, however, we only included patients who met DSM-IV SCID 1 diagnostic criteria for bipolar disorder, independent of any possible personality disorders they may also have had. Moreover, controls did not have any current axis one disorders. The Regional Committee for Medical Research Ethics, and the Norwegian Data Inspectorate approved the study. All participants gave written informed consent. 2.2. Clinical assessment Clinical assessment was carried out by trained psychiatrists and clinical psychologists. Diagnosis was based on the Structured Clinical Interview for DSMIV Axis I disorders (SCID-I). Diagnostic reliability was found to be satisfactory (Ringen et al., 2008) with overall agreement for DSM-IV diagnostic categories of 82% and the overall κ 0.77 (95% CI: 0.60–0.94). Current positive and negative symptoms were rated using the Positive and Negative Syndrome Scale (PANSS) (Kay et al. 1987). Inter-rater reliability was acceptable with intra-class correlation coefficients (Shrout and Fleiss, 1979) for PANSS subscales ranging from 0.71 to 0.73. Participants were defined as currently psychotic if they scored 4 or higher on any one of the following PANSS items: P1, P3, P5, P6, and G9. Use of medication at the time of testing was determined through clinical interview and medical charts. In the patient group, 29 patients (69%) used one or more antipsychotics; 13 patients (31%) used anti-depressants, and 20 patients (48%) used at least one type of mood stabilizers. 2.3. Affective Lability Scale (ALS) Affective lability was measured using the Norwegian version of the Affective Lability Scale (ALS) (Harvey et al., 1989). The ALS includes 54 questions, rated from 0 to 3, and is divided into six sections that examine affective variations between euthymia on the one hand, and depression, elation, anger and anxiety on the other, and that also examine the affective variations between anxiety and depression, and between depression and elation. The total score is the sum of the question's scores divided by 54, thus ranging from 0 to 3, a score closer to 3 indicating greater affective lability.
with five items rated on a five-point Likert scale from 1 (never true) to 5 (very often true).
2.5. Statistical analyses Data were analyzed using the Predictive Analytic software (PASW), Version 18 (formerly SPSS Statistics). Continuous variables were presented as mean 7 standard deviation. As ALS and CTQ were not normally distributed we used non-parametric tests (Spearman's correlation and Mann–Whitney test), when comparing patients and controls on these clinical measures. For the mediation analysis, ALS and CTQ were log transformed before entered into the parametric logistic regression analysis. We also applied the principles for mediation analysis by Baron and Kenny (Baron and Kenny, 1986). As the dependent variable was dichotomous (patients versus controls), logistic regression was performed and Nagelkerke r2 was used to indicate the power of explanation of the model (Nagelkerke, 1991). Lastly, to avoid type 1 error, we corrected for number of childhood sub-groups (physical, sexual and emotional abuse, as well as physical and emotional neglect), using a significance level of 0.01 compared to a standard level of r 0.05. As this was a hypothesis driven study, with a priori ideas on directions, we decided this was sufficient without the potential of losing important data.
3. Results The patient group had a significantly higher CTQ total score compared to the control group (40.44 712.50 versus 29.75 74.29; Mann–Whitney test: z ¼ 2.85, p ¼0.004). Patients also had a significantly higher ALS total score compared to controls (1.01 70.72 versus 0.287 0.33; Mann–Whitney test: z¼ 3.75, p o0.001). Independent sample t-test was conducted comparing ALS scores in patients taking medication (anti-psychotic medication, antidepressants, or mood stabilizers), to patients not taking medication; no significant difference in ALS scores were observed between the groups (f¼ 0.001, t¼0.72, d.f.¼39, p¼0.47). In the patient group, ALS was significantly and positively correlated (Spearman's correlation, [rho]) with CTQ total score (r ¼0.40, p ¼0.009). Moreover, the most significant correlations were observed for emotional abuse (r ¼0.41, p ¼0.007), and emotional neglect (r ¼0.39, p¼ 0.01). No significant associations were shown in the control group only (r o 0.26; p 40.10). Lastly, logistic regression showed that ALS (entered as an independent variable) was significantly associated with the participant group (patients/ control; [Nagelkerke r2 ¼0.36, d.f. ¼1, p ¼0.004]). When both CTQ total score and ALS total score were added into the model as independent variables in the same multivariate regression
Table 1 Correlation between Affective Liability Scale (ALS) total score and childhood trauma. N
Affective Lability Scale (ALS) total score
Patients Physical abuse Sexual abuse Emotional abuse Emotional neglect Physical neglect
42 42 42 42 42
r ¼ 0.33; p¼ 0.035 r ¼ 0.33; p¼ 0.030 r ¼ 0.41; p¼ 0.007n r ¼ 0.39; p ¼0.01n r ¼ 0.18; p ¼0.27
Controls Physical abuse Sexual abuse Emotional abuse Emotional neglect Physical neglect
14 14 14 13 13
r o 0.01; p4 0.9 r ¼ 0.07; p¼ 0.81 r ¼ 0.09; p ¼0.75 r ¼ 0.17; p¼ 0.59 r ¼ 0.26; p ¼0.39
2.4. Childhood Trauma Questionnaire (CTQ) Traumatic events in childhood were rated using a Norwegian version of the Childhood Trauma Questionnaire (CTQ) (Bernstein et al., 2003; Aas et al., 2012a). This is a self-report questionnaire with 28-items (Bernstein et al., 2003), yielding scores on the following five subscales: trauma, emotional abuse, physical abuse, sexual abuse, physical neglect, and emotional neglect. Each subscale is measured
Spearman's correlation (rho); childhood trauma was based on the Childhood Trauma Questionnaire (CTQ) with data divided into sub-groups of scores ranging from 5 to 25; Affective Liability Scale (ALS) total score was based on 54 sub-items from the Affective Liability Scale added together (score ranging from 0 to 143/54); p values: bold ¼ pr 0.05. n
Significant after correction for multiple testing.
Please cite this article as: Aas, M., et al., Affective lability in patients with bipolar disorders is associated with high levels of childhood trauma. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.03.046i
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4.1. Limitations Although there were no significant correlations between medication and ALS scores, we cannot rule out that medication may have influenced our patients' scores on the ALS. Data on childhood trauma were obtained retrospectively with the inherent weakness of retrospective designs. However, the retrospective collection of childhood trauma in patients with severe mental disorders has been found to be a valid and reliable source in obtaining information in previous studies (Fisher et al., 2011). Also our relatively small sample size (patients, n¼ 42; controls, n ¼14) should be taken into consideration, and larger studies should be conducted to further investigate the relationship between childhood trauma, affective lability, and other clinical characteristics of bipolar disorders. Future studies should also investigate pathophysiological mechanisms underlying affective lability in bipolar disorder and the role of childhood trauma.
Role of funding source
Fig. 1. Affective Lability Score (ALS) and CTQ total score. Spearman's correlation: r ¼0.40, p ¼ 0.009. CTQ ¼ Childhood Trauma Questionnaire.
analysis, the model improved (Nagelkerke r2 ¼0.41), and the association level between ALS and subject group dropped (d. f. ¼1, p ¼0.04). The above indicates a relationship between childhood trauma scores and differences in affective lability scores between patients and controls (Table 1, Fig. 1). Seven of the patients presented current psychotic symptoms from the PANSS. Reassuringly when follow-up analysis was conducted excluding patients with a current psychotic episode, the relationship between childhood trauma and ALS score remained, indicating that our findings above were independent of current psychotic symptomatology. Moreover, our results remained the same also when excluding cases with current depressive symptoms (4 Z on PANSS).
4. Discussion Our data demonstrate significant positive associations between scores on the Affective Lability Scale (ALS) and childhood trauma, as measured by the Childhood Trauma Questionnaire (CTQ). This was shown particularly in patients with bipolar disorders with the strongest associations for emotional abuse, followed by emotional neglect. Further, the multivariate regression model indicated a relationship between childhood trauma scores and differences in affective lability scores between patients and controls. Our findings replicate previous studies showing an association between mood instability as measured by the ALS and reports of childhood trauma (Etain et al., 2008; Goodman et al., 2003), with the strongest association for emotional abuse. We have previously shown in a large sample of bipolar patients (n ¼587) that childhood trauma, and specifically emotional abuse, is associated with clinical expression in bipolar disorders, such as rapid cycling course, lifetime history of at least on suicide attempt, as well as number of mood episodes (Etain et al. 2013). Based upon emotional instability being associated with suicide attempts (PalmierClaus et al., 2012), as well as the relationship between rapid cycling and emotional instability (MacKinnon and Pies, 2006), further studies should investigate the relationship between affective lability, childhood trauma and other clinical expressions of bipolar disorders. This should be investigated in larger, and ideally prospective, studies.
This study was funded by grants from the Eastern Norway Health Authority (#2004123, #2006258) and the Research Council of Norway (#167153/V50).
Conflict of interest statement The authors declare that they have no conflict of interest concerning this manuscript.
Acknowledgments We thank the patients who took part in the study and the TOP study researchers who contributed to the data collection. Reference Aas, M., Djurovic, S., Athanasiu, L., Steen, N.E., Agartz, I., Lorentzen, S., Sundet, K., Andreassen, O.A., Melle, I., 2012a. Serotonin transporter gene polymorphism, childhood trauma, and cognition in patients with psychotic disorders. Schizophrenia Bulletin 38, 15–22. Aas, M., Etain, B., Bellivier, F., Henry, C., Lagerberg, T., Ringen, A., Agartz, I., Gard, S., Kahn, J.P., Leboyer, M., Andreassen, O.A., Melle, I., 2013. Additive effects of childhood abuse and cannabis abuse on clinical expressions of bipolar disorders. Psychological Medicine, 1–10. Aas, M., Navari, S., Gibbs, A., Mondelli, V., Fisher, H.L., Morgan, C., Morgan, K., Maccabe, J., Reichenberg, A., Zanelli, J., Fearon, P., Jones, P.B., Murray, R.M., Pariante, C.M., Dazzan, P., 2012b. Is there a link between childhood trauma, cognition, and amygdala and hippocampus volume in first-episode psychosis? Schizophrenia Research 137, 73–79. Aminoff, S.R., Jensen, J., Lagerberg, T.V., Hellvin, T., Sundet, K., Andreassen, O.A., Melle, I., 2012. An association between affective lability and executive functioning in bipolar disorder. Psychiatry Research 198, 58–61. Baron, R.M., Kenny, D.A., 1986. The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. Journal of Personality and Social Psychology 51, 1173–1182. 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 Abuse and Neglect 27, 169–190. Coulston, C.M., Tanious, M., Mulder, R.T., Porter, R.J., Malhi, G.S., 2012. Bordering on bipolar: the overlap between borderline personality and bipolarity. Australian and New Zealand Journal of Psychiatry 46, 506–521. Daruy-Filho, L., Brietzke, E., Lafer, B., Grassi-Oliveira, R., 2011. Childhood maltreatment and clinical outcomes of bipolar disorder. Acta Psychiatrica Scandinavica 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. Journal of Clinical Psychiatry 74, 991–998. Etain, B., Henry, C., Bellivier, F., Mathieu, F., Leboyer, M., 2008. Beyond genetics: childhood affective trauma in bipolar disorder. Bipolar Disorder 10, 867–876.
Please cite this article as: Aas, M., et al., Affective lability in patients with bipolar disorders is associated with high levels of childhood trauma. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.03.046i
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Etain, B., Mathieu, F., Liquet, S., Raust, A., Cochet, B., Richard, J.R., Gard, S., Zanouy, L., Kahn, J.P., Cohen, R.F., Bougerol, T., Henry, C., Leboyer, M., Bellivier, F., 2012. Clinical features associated with trait-impulsiveness in euthymic bipolar disorder patients. Journal of Affective Disorders 144, 240–247. Fisher, H.L., Craig, T.K., Fearon, P., Morgan, K., Dazzan, P., Lappin, J., Hutchinson, G., Doody, G.A., Jones, P.B., McGuffin, P., Murray, R.M., Leff, J., Morgan, C., 2011. Reliability and comparability of psychosis patients' retrospective reports of childhood abuse. Schizophrenia Bulletin 37, 546–553. Gallagher, M., Chiba, A.A., 1996. The amygdala and emotion. Current Opinion in Neurobiology 6, 221–227. Goodman, M., Weiss, D.S., Koenigsberg, H., Kotlyarevsky, V., New, A.S., Mitropoulou, V., Silverman, J.M., O'Flynn, K., Siever, L.J., 2003. The role of childhood trauma in differences in affective instability in those with personality disorders. CNS Spectrums 8, 763–770. Harvey, P.D., Greenberg, B.R., Serper, M.R., 1989. The affective lability scales: development, reliability, and validity. Journal of Clinical Psychology 45, 786–793. Henry, C., Swendsen, J., Van den Bulke, D., Sorbara, F., Demotes-Mainard, J., Leboyer, M., 2003. Emotional hyper-reactivity as a fundamental mood characteristic of manic and mixed states. European Psychiatry 18, 124–128. Henry, C., Van den Bulke, D., Bellivier, F., Roy, I., Swendsen, J., M'Bailara, K., Siever, L.J., Leboyer, M., 2008. Affective lability and affect intensity as core dimensions of bipolar disorders during euthymic period. Psychiatry Research 159, 1–6. Kay, S.R., Fiszbein, A., Opler, L.A., 1987. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261–276.
Marquez, C., Poirier, G.L., Cordero, M.I., Larsen, M.H., Groner, A., Marquis, J., Magistretti, P.J., Trono, D., Sandi, C., 2013. Peripuberty stress leads to abnormal aggression, altered amygdala and orbitofrontal reactivity and increased prefrontal MAOA gene expression. Transl. Psychiatry 3, e216. MacKinnon, D.F., Pies, R., 2006. Affective instability as rapid cycling: theoretical and clinical implications for borderline personality and bipolar spectrum disorders. Bipolar Disorder 8, 1–14. Nagelkerke, N.J.D., 1991. A note on a general definition of the coefficient of determination. Biometrika. Palmier-Claus, J.E., Taylor, P.J., Varese, F., Pratt, D., 2012. Does unstable mood increase risk of suicide? Theory, research and practice. Journal of Affective Disorders 143, 5–15. Ringen, P.A., Lagerberg, T.V., Birkenaes, A.B., Engen, J., Faerden, A., Jonsdottir, H., Nesvag, R., Friis, S., Opjordsmoen, S., Larsen, F., Melle, I., Andreassen, O.A., 2008. Differences in prevalence and patterns of substance use in schizophrenia and bipolar disorder. Psychological Medicine 38, 1241–1249. Shrout, P.E., Fleiss, J.L., 1979. Intraclass correlations: uses in assessing rater reliability. Schizophrenia Bulletin 86, 420–428. van Harmelen, A.L., van Tol, M.J., Demenescu, L.R., van der Wee, N.J., Veltman, D.J., Aleman, A., van Buchem, M.A., Spinhoven, P., Penninx, B.W., Elzinga, B.M., 2013. Enhanced amygdala reactivity to emotional faces in adults reporting childhood emotional maltreatment. Social Cognitive and Affective Neuroscience 8, 362–369.
Please cite this article as: Aas, M., et al., Affective lability in patients with bipolar disorders is associated with high levels of childhood trauma. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.03.046i
