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Emotional hyperreactivity as a core dimension of manic and mixed states
Psychiatry Research 197 (2012) 227–230
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Emotional hyperreactivity as a core dimension of manic and mixed states Katia M'Bailara a, b,⁎, Thierry Atzeni a, Francesc Colom c, Joel Swendsen d, Sébastien Gard b, Alain Desage b, Chantal Henry e, f, g a
Laboratory of Psychology, EA4139, University Bordeaux Segalen, 3ter Place de la Victoire, Bordeaux, France Hospital Charles Perrens, 121 rue de la Béchade, Bordeaux, France c Bipolar Disorders Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Spain d CNRS 5231, University Bordeaux Segalen, 146 rue Léo Saignat, Bordeaux, France e AP-HP, Henri Mondor-Albert Chenevier Hospitals, Department of Psychiatry, Creteil, F-94000, France f INSERM, U 955, IMRB, Department of Genetics, Psychiatric Genetics, Creteil, F-94000, France g University of Paris, Paris 12, France b
a r t i c l e
i n f o
Article history: Received 7 February 2011 Received in revised form 30 August 2011 Accepted 1 December 2011 Keywords: Bipolar disorders Mania Mixed states Emotional hyperreactivity
a b s t r a c t Despite its obvious importance in mood disorders, characterization of emotional reactivity has been neglected in bipolar disorders. Concerning manic states and the current classification, the main criterion is the presence of an elevated or expansive mood. In contrast to this characteristic and often prolonged mood state, emotional reactivity refers to a brief evoked response to salient emotional stimuli. The goal of this study was to assess the intensity of emotional responses triggered by viewing slides in bipolar patients with manic or mixed states. Our hypothesis was that all emotional responses are exacerbated, whatever the valence of the stimuli. We compared 33 patients with manic or mixed states with 33 matched euthymic patients and 33 healthy control subjects. Arousal and attribution of valence were assessed while subjects viewed slides taken from the International Affective Picture System (positive, neutral and negative slides). Patients with manic or mixed states reported a higher arousal when viewing all types of slides in comparison with the other groups. Concerning attribution of valence, patients with manic or mixed states assessed neutral slides as more pleasant. When bipolar patients with manic and mixed states are placed in front of positive, neutral and negative slides, the slides trigger a higher intensity of emotions, whatever the valence of the emotional stimuli. These results strengthen the importance of emotional hyperreactivity as a core dimension in manic and mixed states in bipolar disorder. © 2012 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Despite its obvious importance in mood disorders, the characterization of emotional reactivity has been neglected in the spectrum of bipolar disorders. The main criterion for bipolar disorder is the occurrence of a durable mood disturbance: sadness during depressive episodes and elevated or expansive mood in manic states. In contrast to this lengthy duration of a mood state, emotional reactivity refers to a brief evoked response to salient emotional stimuli (Henry et al., in press). Generally, moods and emotions have been seen as interconnected, with the idea that moods may potentiate correspondingly valenced emotions. Thus, sad mood is thought to exacerbate emotional reactivity when subjects are exposed to negative stimuli, and euphoria is thought to trigger more intensive responses when subjects are confronted with positive stimuli. However, the data do not support this hypothesis (Rottenberg et al., 2005). Moreover, most manic states not only exhibit euphoric ⁎ Corresponding author at: Laboratory of Psychology, EA4139, University Bordeaux Segalen, 3ter place de la Victoire, Bordeaux, France. Tel.: +33 5 57 57 30 27; fax: +33 1 57 57 19 77. E-mail address: [email protected] (K. M'Bailara). 0165-1781/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.psychres.2011.12.003
mood but also a characteristically high lability of affect states. Beyond the euphoric response, an unresolved issue is the ability of patients to respond to external stimuli. This issue is critical because the level of adaptation of an individual depends on his or her ability to respond to environmental stimuli. Mood in manic episodes is characterized by high lability in most patients. Goodwin and Jamison (Goodwin and Jamison, 2007) found that the most frequent emotions during the manic state were irritability (71%), followed by euphoria (63%), expansiveness (60%), mood lability (49%) and depression (46%). Factor analyses assessing the dimensions involved in manic states revealed the presence of a depressed component in most manic episodes, regardless of whether they were pure or mixed states (Cassidy et al., 1998; Dilsaver et al., 1999; Azorin et al., 2000; Swann et al., 2001; Rossi et al., 2001; Gonzalez-Pinto et al., 2003; Suppes et al., 2005; Sato et al., 2002). Given this high variability in the tonality of mood, it is important to understand what happens in terms of emotional reactivity. In a previous study, we showed that patients with a manic or mixed state reported experiencing emotions more intensely than usual (Henry et al., 2003). The aim of this experiment was to study emotional response (arousal and attribution of valence) triggered by positive, negative
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or neutral slides in manic and mixed states in bipolar patients and to compare responses to those in euthymic bipolar patients and control subjects. Our hypothesis was that all emotional responses would be exaggerated in manic and mixed states, whatever the valence of the stimuli. 2. Method 2.1. Participants and clinical assessment The sample included 99 subjects who were subdivided as follows: 33 were bipolar patients during a phase of remission (euthymic group), 33 had a manic (n = 16), hypomanic (n = 10) or mixed (n = 7) episode as defined by DSM-IV (for convenience, all these patients are referred to as the manic group, see Section 4 for more details), and 33 were control subjects. All subjects were assessed by a trained psychologist using the Diagnostic Interview for Genetic Studies (DIGS) to provide DSM-IV diagnoses (Nurnberger et al., 1994), and the severity of depressive and manic symptoms was quantified using the Montgomery and Åsberg Depression Rating Scale (MADRS) (Montgomery and Asberg, 1979) as well as the Bech-Rafaelsen Mania Rating Scale (MAS) (Bech et al., 1978). The euthymic bipolar group included patients who did not meet DSM-IV criteria for a full episode at the time of evaluation and who had a MADRS score below 12 and a MAS score below 4. The control group, which was recruited by advertising, included participants without any psychiatric axis I disorder. The investigation was approved by the ethics committee of the University Hospital Center (Toulouse, France) for clinical research. All subjects provided written informed consent to participate. 2.2. Experimental design Emotional response was evaluated by inducing emotions through emotional visual stimuli. Participants were placed in a room with filtered light in front of a computer screen (1 m) on which a series of 18 slides (6 positive, 6 neutral and 6 negative) from the International Affective Picture System (IAPS) (Lang et al., 1995) was presented randomly. The set consisted of a succession of six trios, each trio consisting of a positive slide, a neutral slide, and a negative slide. The order of the slides within the set was counterbalanced, so there were six different orders of presentation. Each slide was presented for 10 s, followed by a dark gray screen, which was also presented for 10 s. The subjects were asked to evaluate valence and arousal for each slide using the SelfAssessment of Manikin (SAM) (Lang et al., 1995), a 9-point visual analog scale. Arousal describes the intensity of emotion triggered by slides, and valence the pleasantness or hedonic value (Stickel et al., 2009). Regarding valence, low scores were indicative of unpleasant slides, and high scores were indicative of pleasant slides. For arousal, low scores were indicative of low intensity of emotion, and high scores were indicative of strong emotion. 2.3. Statistical analysis Analyses were carried out with the Statistical Package for the Social Sciences (SPSS, version 14 for Windows). The χ2 test was used to compare categorical qualitative data. Analysis of variance (ANOVA) was used to compare averages of quantitative continuous variables. Post hoc Tukey HSD (honestly significant difference) tests for pairwise comparisons were used to determine whether there was any significant difference among groups in terms of valence and arousal evaluation. Although there is empirical evidence that ANOVA is quite robust regarding violation of the assumption of normality (Schmider et al., 2010) and departures from the assumption of homogeneity of variance (Grissom, 2000), we systematically checked the results of the ANOVA using appropriate nonparametric tests (Kruskal–Wallis H and Mann–Whitney U tests) in case of significant deviations from normal distribution and heterogeneity of variance. The normality of distribution of each variable was assessed using a normal probability plot and the Shapiro–Wilk test. The homogeneity of variance was assessed using Levene's test. For all tests, significance was set at p b 0.05, two-tailed.
3. Results
p b 0.001, η2 = 0.75. Posthoc analyses using Tukey's HSD revealed that on the MADRS, the manic group (mean = 10.42, S.D. = 5.77) differed significantly from the euthymic (mean = 1.6, S.D. = 2.91) and control (mean = 0.18, S.D. = 0.72) groups. The pattern was the same for the MAS, with a mean of 14.9 (S.D. = 6.6) for manic, 0.9 (S.D. = 1.4) for euthymic, and 0.2 (S.D. = 0.6) for control subjects. There was no statistical difference between euthymic and control groups regarding these two scales. 3.2. Valence evaluation There was no group effect concerning the assessment of positive, F b 1 and negative slides, F b 1 (Fig. 1). There was a group effect only for the assessment of neutral slides, F(2, 96) = 9.2, p > 0.01, η 2 = 0.16. Post-hoc analyses using Tukey's HSD (see Table 1) revealed that the mean scores of the manic (mean= 5.3, S.D. = 1.3) and euthymic (mean = 4.7, S.D. = 1,1) groups were statistically different from those of the controls (mean = 4.0, S.D. = 1.3). Manic and euthymic patients expressed a more pleasant valence for neutral slides than controls. 3.3. Arousal evaluation There was a group effect for the evaluation of all types of slides (Fig. 2). We found differences for positive (F(2, 96) = 9.7, p b 0.001, η 2 = 0.17), neutral (F(2, 96) = 16.1, p b 0.001, η 2 = 0.25) and negative (F(2, 96) = 5.8, p b 0.001, η 2 = 0.11) slides. The manic group showed higher mean arousal scores than the euthymic and control groups. Mean arousal scores for manic, euthymic and control subjects were, respectively, 5.5 (S.D. = 1.7), 4.0 (S.D. = 2), and 3.8 (S.D. = 1.4) for positive stimuli; 3.7 (S.D. = 2.3), 2.1 (S.D. = 1.7), and 1.3 (S.D. = 1.2) for neutral stimuli; and 6.3 (S.D. = 1.6), 4.9 (S.D. = 1.8), and 5.3 (S.D. = 1.7) for negative stimuli. All differences between manic and euthymic groups were significant (see Table 1). The manic group also differed significantly from the control group with regard to positive and neutral stimuli (see Table 1) and showed a strong tendency toward a difference for negative stimuli (p = 0.056, d = 0.59). A series of complementary analyses was performed to rule out the possibility that some of our results could stem from initial differences between mixed states, manic states and hypomanic patients. Oneway ANOVAs were performed to assess whether there were differences in the evaluation of arousal and valence among the three groups of patients. Regarding the evaluation of valence, there was
** **
8
(Hypo)manic patients Euthymic patients
6
Controls subjects 4
3.1. Analysis of sample characteristics 2
We conducted analyses concerning sociodemographic variables and mood states on the three groups. There was no significant difference between the groups regarding age, F(2, 96) = 0.06, and all groups were similar regarding the proportion of men and women (χ2 =0.3, d.f. = 1, p = 0.6) and marital status (χ² = 0.9, d.f. = 2, p = 0.6). Manic patients were more symptomatic than euthymic bipolar patients and controls. The group effect was statistically significant both for the MADRS, F(2, 96) =72.08, p b 0.001, η2 = 0.60, and the MAS, F(2, 96) = 145.28,
0 positive valence
neutral valence
negative valence
Fig. 1. Level of valence and arousal for manic or mixed states, euthymic bipolar patients and control subjects according to the types of slides. **Differences between manic or mixed states and the other groups, p b 0.01.
K. M'Bailara et al. / Psychiatry Research 197 (2012) 227–230 Table 1 Results of pairwise comparisons (Tukey HSD) between each group for valence and arousal for the assessment of positive, neutral and negative slides. Emotional response
Pairwise comparisons
Manicb/ euthymic Manic/control Euthymic/ control Neutral Manic/euthymic Manic/control Euthymic/ control Negative Manic/euthymic Manic/control Euthymic/ control Positive Manic/ euthymic Manic/control Euthymic/ control Neutral Manic/ euthymic Manic/control Euthymic/ control Negative Manic/ euthymic Manic/control Euthymic/ control
Valence Positive
Arousal
a b
Mean 95% CI difference LBa
p
d
− 0.49 0.86 0.79
0.14
0.01 − 0.176
− 0.67 0.69 0.99 − 0.85 0.5 0.81
0.01 0.16
0.54 1.288 0.747
− 0.18 1.26 0.18 0.57 2.01 0.001⁎⁎⁎ 0.03 1.47 0.039⁎
0.45 0.99 0.64
0.015 0.02 0.005
− 0.56 0.59 0.99 − 0.55 0.59 0.99 − 0.57 0.58 0.99
0.01 0.02 0.01
1.525
0.51 2.54 0.001⁎⁎⁎ 0.82
1.702 0.177
0.69 2.71 0.001⁎⁎⁎ 1.07 − 0.83 1.19 0.91 0.1
1.606
0.55 2.66 0.001⁎⁎⁎ 0.79
2.489 0.883
1.43 3.55 0.001⁎⁎⁎ 1.34 − 0.17 1.94 0.12 0.6
0.985 − 0.409
0.39 2.4
0.01⁎⁎
− 0.02 1.99 0.06 − 1.41 0.59 0.6
0.8 0.59 0.23
LB = lower bound, UB = upper bound. Manic : group including patients with manic or mixed states. ⁎ p b .05. ⁎⁎ p b .01. ⁎⁎⁎ p b .001.
no significant effect of the type of manic patients concerning the assessment of positive slides, F(2, 30) = 0.89, η 2 = 0.06; neutral slides, F(2, 30) = 0.51, η 2 = 0.001; and negative slides, F(2, 30) = 2.29, p = 0.08, η 2 = 0.18. Concerning arousal, there were also no significant differences among the three groups of manic patients concerning the assessment of positive slides, F(2, 30) = 0.82, η 2 = 0.05; neutral slides, F(2, 30) = 1.26, p = 0.29, η 2 = 0.08; and negative slides, F(2, 30) = 1.65, p = 0.21, η 2 = 0.10. Post-hoc analyses using Tukey's HSD test revealed no significant difference at an alpha-corrected level
8
** **
** ** **
6
4
2
0 positive arousal
neutral arousal
of 0.05 between the three groups of manic patients on any kind of stimuli either for valence or arousal evaluation. 4. Discussion
UBa
0.186
1.394
229
negative arousal
Fig. 2. Level of valence and arousal for manic or mixed states, euthymic bipolar patients and control subjects according to the types of slides. **Differences between manic or mixed states and the other groups, p b 0.01.
Using an emotional induction protocol, we found that patients with manic or mixed states attributed the correct valence compared with the responses of euthymic and normal control groups when slides were positive or negative, but they considered neutral slides as more pleasant. Concerning the second dimension of emotion, manic patients reported higher arousal compared with euthymic subjects whatever the valence of the slides — positive, neutral or negative. The same pattern was observed for positive and neutral slides when manic patients were compared with normal controls, and there was a trend for patients with manic or mixed states to experience higher arousal than controls for negative slides. The standardized effect size (d = 0.59) shows that the assessment of negative stimuli by patients in manic or mixed states was nearly half a standard deviation higher than the assessment made by controls, which seems considerable. The explanation for the failure of the apparent difference to reach the level of statistical significance could reflect a lack of statistical power due to the small size of our samples. To our knowledge, this is the first study using an emotioninduction protocol to investigate emotional reactivity among bipolar patients with manic or mixed states compared with euthymic bipolar patients and controls. However, a previous study using a self-report scale showed that all patients with manic or mixed states felt emotions more intensely (Henry et al., 2003). Thereafter, we validated a scale to explore thymic states using a dimensional approach (Henry et al., 2007a,b,c, 2008). Among the dimensions assessed, the MATHYS scale explored the variation of emotional reactivity during bipolar mood episodes, and showed that manic and mixed states were characterized by an emotional hyperreactivity, meaning that patients in these states report feeling emotions with an unusual intensity (Henry et al., 2007a, b,c). Classically, manic patients are considered to be more reactive to positive emotional stimuli, so they are more interested in pleasurable activities. However, this classic view of manic states is now challenged because most manic states display at least emotional lability and, most of the time, dysphoric features (Goodwin and Jamison, 2007). Dysphoric manic episodes have been shown to be associated with an elevated risk of suicidality (Goldberg et al., 1999). Therefore, manic episodes cannot be considered only as euphoric states where patients are consistently involved in pleasant activities. Functional brain imaging studies provide information about the mechanisms underlying this emotional reactivity. There have been very few functional magnetic resonance imaging (fMRI) studies of bipolar mania, likely due in part to the difficulty of scanning these subjects. However, most of the studies that used activation paradigms to target the amygdala, the main structure involved in emotional processes, have shown significantly increased activity in manic patients compared with healthy subjects (Chen, 2003; Altshuler et al., 2005). This overactivation could be due to a reduced VLPF (ventrolateral prefrontal cortex) regulation exerting an inhibitory action (Foland et al., 2008). Thus, brain-imaging may help in the identification of pathophysiological processes underlying abnormal emotional reactivity in manic episodes. To our knowledge, only one study has assessed the activation of the amygdala in manic patients as a function of the valence of the stimuli. Bermpohl et al. (2009) explored the response of the amygdala to affective stimuli in manic and healthy control subjects using slides extracted from the IAPS. Manic patients had a higher response in the left amygdala during the viewing of positive versus neutral slides. In that study, however, the pattern of response was the same for positive and negative slides in manic patients, even though the response was slightly lower for the latter. This lack of a significant
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difference could be due to the relatively small sample size (n = 10 subjects in each group). Our results also show that manic patients attribute a more pleasant valence to neutral slides. This suggests that they are more optimistic in the manner in which they perceive the environment when it is not perfectly codified. It does not mean, however, that they are less reactive to negative events. This pilot study adds more weight to the various sets of evidence (clinical, experimental and brain imaging) indicating that global emotional hyperreactivity is a characteristic of manic and mixed states. Amplification of the emotional response is involved in all types of stimulation. This amplified emotional response could represent the common characteristics of manic and mixed states (Lyon et al., 1999; Henry et al., 2003, Henry et al., 2007a,b,c; Elliott et al., 2004; Besnier et al., 2011). However, the difference could stem from the global tonality of affects, which are more positive in the first case and darker in mixed states. This investigation now needs to be performed in a larger group of patients to take into account the intensity of manic and depressive symptoms. Moreover, it would be pertinent to include objective components of the emotional response such as variations in skin conductance and heart rate, in order to obtain a plausible and exhaustive explanatory model of emotional hyperreactivity. However, recording these variables requires a large sample of patients since pharmaceutical treatments may confound the results. Our data also suggest that subjects in the manic and mixed groups regarded neutral slides in a more favorable light than control and euthymic bipolar patients. This in itself is a noteworthy finding, as it indicates that euphoria and irritability are not the only triggers in manic, hypomanic or mixed patients. These findings also show that neutral stimuli can trigger many emotions. Emotional reactivity is an efficient concept for clinicians because it can provide diagnostic assistance. Indeed, many manic, hypomanic and mixed patients cannot recognize themselves in the classical DSM-IV criteria (euphoria or irritability), and few patients complain about their emotional hyperreactivity when stimuli presented to them are positive or negative. The present findings might therefore help clinicians to improve their diagnostic procedure. They are also interesting for patients in that they provide better understanding of their own state and help them to recognize it as pathological. Role of funding source This work was funded by the “programme hospitalier de la recherche clinique” (PHRC, 2003). Katia M'bailara received a grant from the French Ministry of Research. Francesc Colom is grateful for the support and funding of the Spanish Ministry of Health, Instituto de Salud Carlos III, CIBER-SAM. Dr. Colom is also funded by the Spanish Ministry of Science and Innovation, Instituto Carlos III, through a “Miguel Servet” postdoctoral contract (CP08/00140) and a FIS (PS09/01044). Acknowledgments We received the support of the foundation FondaMental. References Altshuler, L., Bookheimer, S., Proenza, M.A., Townsend, J., Sabb, F., Firestine, A., Cohen, M.S., 2005. Increased amygdala activation during mania: a functional magnetic resonance imaging study. American Journal of Psychiatry 162, 1211–1213. Azorin, J.M., Hantouche, E.G., Akiskal, H.S., Bourgeois, M.L., Allilaire, J.F., Sechter, D., Châtenet-Duchêne, L., 2000. Structure factorielle du syndrome maniaque: revue de la littérature et résultats de l'étude française ‘EPIMAN’. Annales Médico-Psychologiques 158, 279–289. Bech, P., Rafaelsen, O.J., Kramp, P., Bolwig, T.G., 1978. The mania rating scale: scale construction and inter-observer agreement. Neuropharmacology 17, 430–431.
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Emotional hyperreactivity as a core dimension of manic and mixed states Katia M'Bailara a, b,⁎, Thierry Atzeni a, Francesc Colom c, Joel Swendsen d, Sébastien Gard b, Alain Desage b, Chantal Henry e, f, g a
Laboratory of Psychology, EA4139, University Bordeaux Segalen, 3ter Place de la Victoire, Bordeaux, France Hospital Charles Perrens, 121 rue de la Béchade, Bordeaux, France c Bipolar Disorders Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Spain d CNRS 5231, University Bordeaux Segalen, 146 rue Léo Saignat, Bordeaux, France e AP-HP, Henri Mondor-Albert Chenevier Hospitals, Department of Psychiatry, Creteil, F-94000, France f INSERM, U 955, IMRB, Department of Genetics, Psychiatric Genetics, Creteil, F-94000, France g University of Paris, Paris 12, France b
a r t i c l e
i n f o
Article history: Received 7 February 2011 Received in revised form 30 August 2011 Accepted 1 December 2011 Keywords: Bipolar disorders Mania Mixed states Emotional hyperreactivity
a b s t r a c t Despite its obvious importance in mood disorders, characterization of emotional reactivity has been neglected in bipolar disorders. Concerning manic states and the current classification, the main criterion is the presence of an elevated or expansive mood. In contrast to this characteristic and often prolonged mood state, emotional reactivity refers to a brief evoked response to salient emotional stimuli. The goal of this study was to assess the intensity of emotional responses triggered by viewing slides in bipolar patients with manic or mixed states. Our hypothesis was that all emotional responses are exacerbated, whatever the valence of the stimuli. We compared 33 patients with manic or mixed states with 33 matched euthymic patients and 33 healthy control subjects. Arousal and attribution of valence were assessed while subjects viewed slides taken from the International Affective Picture System (positive, neutral and negative slides). Patients with manic or mixed states reported a higher arousal when viewing all types of slides in comparison with the other groups. Concerning attribution of valence, patients with manic or mixed states assessed neutral slides as more pleasant. When bipolar patients with manic and mixed states are placed in front of positive, neutral and negative slides, the slides trigger a higher intensity of emotions, whatever the valence of the emotional stimuli. These results strengthen the importance of emotional hyperreactivity as a core dimension in manic and mixed states in bipolar disorder. © 2012 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Despite its obvious importance in mood disorders, the characterization of emotional reactivity has been neglected in the spectrum of bipolar disorders. The main criterion for bipolar disorder is the occurrence of a durable mood disturbance: sadness during depressive episodes and elevated or expansive mood in manic states. In contrast to this lengthy duration of a mood state, emotional reactivity refers to a brief evoked response to salient emotional stimuli (Henry et al., in press). Generally, moods and emotions have been seen as interconnected, with the idea that moods may potentiate correspondingly valenced emotions. Thus, sad mood is thought to exacerbate emotional reactivity when subjects are exposed to negative stimuli, and euphoria is thought to trigger more intensive responses when subjects are confronted with positive stimuli. However, the data do not support this hypothesis (Rottenberg et al., 2005). Moreover, most manic states not only exhibit euphoric ⁎ Corresponding author at: Laboratory of Psychology, EA4139, University Bordeaux Segalen, 3ter place de la Victoire, Bordeaux, France. Tel.: +33 5 57 57 30 27; fax: +33 1 57 57 19 77. E-mail address: [email protected] (K. M'Bailara). 0165-1781/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.psychres.2011.12.003
mood but also a characteristically high lability of affect states. Beyond the euphoric response, an unresolved issue is the ability of patients to respond to external stimuli. This issue is critical because the level of adaptation of an individual depends on his or her ability to respond to environmental stimuli. Mood in manic episodes is characterized by high lability in most patients. Goodwin and Jamison (Goodwin and Jamison, 2007) found that the most frequent emotions during the manic state were irritability (71%), followed by euphoria (63%), expansiveness (60%), mood lability (49%) and depression (46%). Factor analyses assessing the dimensions involved in manic states revealed the presence of a depressed component in most manic episodes, regardless of whether they were pure or mixed states (Cassidy et al., 1998; Dilsaver et al., 1999; Azorin et al., 2000; Swann et al., 2001; Rossi et al., 2001; Gonzalez-Pinto et al., 2003; Suppes et al., 2005; Sato et al., 2002). Given this high variability in the tonality of mood, it is important to understand what happens in terms of emotional reactivity. In a previous study, we showed that patients with a manic or mixed state reported experiencing emotions more intensely than usual (Henry et al., 2003). The aim of this experiment was to study emotional response (arousal and attribution of valence) triggered by positive, negative
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or neutral slides in manic and mixed states in bipolar patients and to compare responses to those in euthymic bipolar patients and control subjects. Our hypothesis was that all emotional responses would be exaggerated in manic and mixed states, whatever the valence of the stimuli. 2. Method 2.1. Participants and clinical assessment The sample included 99 subjects who were subdivided as follows: 33 were bipolar patients during a phase of remission (euthymic group), 33 had a manic (n = 16), hypomanic (n = 10) or mixed (n = 7) episode as defined by DSM-IV (for convenience, all these patients are referred to as the manic group, see Section 4 for more details), and 33 were control subjects. All subjects were assessed by a trained psychologist using the Diagnostic Interview for Genetic Studies (DIGS) to provide DSM-IV diagnoses (Nurnberger et al., 1994), and the severity of depressive and manic symptoms was quantified using the Montgomery and Åsberg Depression Rating Scale (MADRS) (Montgomery and Asberg, 1979) as well as the Bech-Rafaelsen Mania Rating Scale (MAS) (Bech et al., 1978). The euthymic bipolar group included patients who did not meet DSM-IV criteria for a full episode at the time of evaluation and who had a MADRS score below 12 and a MAS score below 4. The control group, which was recruited by advertising, included participants without any psychiatric axis I disorder. The investigation was approved by the ethics committee of the University Hospital Center (Toulouse, France) for clinical research. All subjects provided written informed consent to participate. 2.2. Experimental design Emotional response was evaluated by inducing emotions through emotional visual stimuli. Participants were placed in a room with filtered light in front of a computer screen (1 m) on which a series of 18 slides (6 positive, 6 neutral and 6 negative) from the International Affective Picture System (IAPS) (Lang et al., 1995) was presented randomly. The set consisted of a succession of six trios, each trio consisting of a positive slide, a neutral slide, and a negative slide. The order of the slides within the set was counterbalanced, so there were six different orders of presentation. Each slide was presented for 10 s, followed by a dark gray screen, which was also presented for 10 s. The subjects were asked to evaluate valence and arousal for each slide using the SelfAssessment of Manikin (SAM) (Lang et al., 1995), a 9-point visual analog scale. Arousal describes the intensity of emotion triggered by slides, and valence the pleasantness or hedonic value (Stickel et al., 2009). Regarding valence, low scores were indicative of unpleasant slides, and high scores were indicative of pleasant slides. For arousal, low scores were indicative of low intensity of emotion, and high scores were indicative of strong emotion. 2.3. Statistical analysis Analyses were carried out with the Statistical Package for the Social Sciences (SPSS, version 14 for Windows). The χ2 test was used to compare categorical qualitative data. Analysis of variance (ANOVA) was used to compare averages of quantitative continuous variables. Post hoc Tukey HSD (honestly significant difference) tests for pairwise comparisons were used to determine whether there was any significant difference among groups in terms of valence and arousal evaluation. Although there is empirical evidence that ANOVA is quite robust regarding violation of the assumption of normality (Schmider et al., 2010) and departures from the assumption of homogeneity of variance (Grissom, 2000), we systematically checked the results of the ANOVA using appropriate nonparametric tests (Kruskal–Wallis H and Mann–Whitney U tests) in case of significant deviations from normal distribution and heterogeneity of variance. The normality of distribution of each variable was assessed using a normal probability plot and the Shapiro–Wilk test. The homogeneity of variance was assessed using Levene's test. For all tests, significance was set at p b 0.05, two-tailed.
3. Results
p b 0.001, η2 = 0.75. Posthoc analyses using Tukey's HSD revealed that on the MADRS, the manic group (mean = 10.42, S.D. = 5.77) differed significantly from the euthymic (mean = 1.6, S.D. = 2.91) and control (mean = 0.18, S.D. = 0.72) groups. The pattern was the same for the MAS, with a mean of 14.9 (S.D. = 6.6) for manic, 0.9 (S.D. = 1.4) for euthymic, and 0.2 (S.D. = 0.6) for control subjects. There was no statistical difference between euthymic and control groups regarding these two scales. 3.2. Valence evaluation There was no group effect concerning the assessment of positive, F b 1 and negative slides, F b 1 (Fig. 1). There was a group effect only for the assessment of neutral slides, F(2, 96) = 9.2, p > 0.01, η 2 = 0.16. Post-hoc analyses using Tukey's HSD (see Table 1) revealed that the mean scores of the manic (mean= 5.3, S.D. = 1.3) and euthymic (mean = 4.7, S.D. = 1,1) groups were statistically different from those of the controls (mean = 4.0, S.D. = 1.3). Manic and euthymic patients expressed a more pleasant valence for neutral slides than controls. 3.3. Arousal evaluation There was a group effect for the evaluation of all types of slides (Fig. 2). We found differences for positive (F(2, 96) = 9.7, p b 0.001, η 2 = 0.17), neutral (F(2, 96) = 16.1, p b 0.001, η 2 = 0.25) and negative (F(2, 96) = 5.8, p b 0.001, η 2 = 0.11) slides. The manic group showed higher mean arousal scores than the euthymic and control groups. Mean arousal scores for manic, euthymic and control subjects were, respectively, 5.5 (S.D. = 1.7), 4.0 (S.D. = 2), and 3.8 (S.D. = 1.4) for positive stimuli; 3.7 (S.D. = 2.3), 2.1 (S.D. = 1.7), and 1.3 (S.D. = 1.2) for neutral stimuli; and 6.3 (S.D. = 1.6), 4.9 (S.D. = 1.8), and 5.3 (S.D. = 1.7) for negative stimuli. All differences between manic and euthymic groups were significant (see Table 1). The manic group also differed significantly from the control group with regard to positive and neutral stimuli (see Table 1) and showed a strong tendency toward a difference for negative stimuli (p = 0.056, d = 0.59). A series of complementary analyses was performed to rule out the possibility that some of our results could stem from initial differences between mixed states, manic states and hypomanic patients. Oneway ANOVAs were performed to assess whether there were differences in the evaluation of arousal and valence among the three groups of patients. Regarding the evaluation of valence, there was
** **
8
(Hypo)manic patients Euthymic patients
6
Controls subjects 4
3.1. Analysis of sample characteristics 2
We conducted analyses concerning sociodemographic variables and mood states on the three groups. There was no significant difference between the groups regarding age, F(2, 96) = 0.06, and all groups were similar regarding the proportion of men and women (χ2 =0.3, d.f. = 1, p = 0.6) and marital status (χ² = 0.9, d.f. = 2, p = 0.6). Manic patients were more symptomatic than euthymic bipolar patients and controls. The group effect was statistically significant both for the MADRS, F(2, 96) =72.08, p b 0.001, η2 = 0.60, and the MAS, F(2, 96) = 145.28,
0 positive valence
neutral valence
negative valence
Fig. 1. Level of valence and arousal for manic or mixed states, euthymic bipolar patients and control subjects according to the types of slides. **Differences between manic or mixed states and the other groups, p b 0.01.
K. M'Bailara et al. / Psychiatry Research 197 (2012) 227–230 Table 1 Results of pairwise comparisons (Tukey HSD) between each group for valence and arousal for the assessment of positive, neutral and negative slides. Emotional response
Pairwise comparisons
Manicb/ euthymic Manic/control Euthymic/ control Neutral Manic/euthymic Manic/control Euthymic/ control Negative Manic/euthymic Manic/control Euthymic/ control Positive Manic/ euthymic Manic/control Euthymic/ control Neutral Manic/ euthymic Manic/control Euthymic/ control Negative Manic/ euthymic Manic/control Euthymic/ control
Valence Positive
Arousal
a b
Mean 95% CI difference LBa
p
d
− 0.49 0.86 0.79
0.14
0.01 − 0.176
− 0.67 0.69 0.99 − 0.85 0.5 0.81
0.01 0.16
0.54 1.288 0.747
− 0.18 1.26 0.18 0.57 2.01 0.001⁎⁎⁎ 0.03 1.47 0.039⁎
0.45 0.99 0.64
0.015 0.02 0.005
− 0.56 0.59 0.99 − 0.55 0.59 0.99 − 0.57 0.58 0.99
0.01 0.02 0.01
1.525
0.51 2.54 0.001⁎⁎⁎ 0.82
1.702 0.177
0.69 2.71 0.001⁎⁎⁎ 1.07 − 0.83 1.19 0.91 0.1
1.606
0.55 2.66 0.001⁎⁎⁎ 0.79
2.489 0.883
1.43 3.55 0.001⁎⁎⁎ 1.34 − 0.17 1.94 0.12 0.6
0.985 − 0.409
0.39 2.4
0.01⁎⁎
− 0.02 1.99 0.06 − 1.41 0.59 0.6
0.8 0.59 0.23
LB = lower bound, UB = upper bound. Manic : group including patients with manic or mixed states. ⁎ p b .05. ⁎⁎ p b .01. ⁎⁎⁎ p b .001.
no significant effect of the type of manic patients concerning the assessment of positive slides, F(2, 30) = 0.89, η 2 = 0.06; neutral slides, F(2, 30) = 0.51, η 2 = 0.001; and negative slides, F(2, 30) = 2.29, p = 0.08, η 2 = 0.18. Concerning arousal, there were also no significant differences among the three groups of manic patients concerning the assessment of positive slides, F(2, 30) = 0.82, η 2 = 0.05; neutral slides, F(2, 30) = 1.26, p = 0.29, η 2 = 0.08; and negative slides, F(2, 30) = 1.65, p = 0.21, η 2 = 0.10. Post-hoc analyses using Tukey's HSD test revealed no significant difference at an alpha-corrected level
8
** **
** ** **
6
4
2
0 positive arousal
neutral arousal
of 0.05 between the three groups of manic patients on any kind of stimuli either for valence or arousal evaluation. 4. Discussion
UBa
0.186
1.394
229
negative arousal
Fig. 2. Level of valence and arousal for manic or mixed states, euthymic bipolar patients and control subjects according to the types of slides. **Differences between manic or mixed states and the other groups, p b 0.01.
Using an emotional induction protocol, we found that patients with manic or mixed states attributed the correct valence compared with the responses of euthymic and normal control groups when slides were positive or negative, but they considered neutral slides as more pleasant. Concerning the second dimension of emotion, manic patients reported higher arousal compared with euthymic subjects whatever the valence of the slides — positive, neutral or negative. The same pattern was observed for positive and neutral slides when manic patients were compared with normal controls, and there was a trend for patients with manic or mixed states to experience higher arousal than controls for negative slides. The standardized effect size (d = 0.59) shows that the assessment of negative stimuli by patients in manic or mixed states was nearly half a standard deviation higher than the assessment made by controls, which seems considerable. The explanation for the failure of the apparent difference to reach the level of statistical significance could reflect a lack of statistical power due to the small size of our samples. To our knowledge, this is the first study using an emotioninduction protocol to investigate emotional reactivity among bipolar patients with manic or mixed states compared with euthymic bipolar patients and controls. However, a previous study using a self-report scale showed that all patients with manic or mixed states felt emotions more intensely (Henry et al., 2003). Thereafter, we validated a scale to explore thymic states using a dimensional approach (Henry et al., 2007a,b,c, 2008). Among the dimensions assessed, the MATHYS scale explored the variation of emotional reactivity during bipolar mood episodes, and showed that manic and mixed states were characterized by an emotional hyperreactivity, meaning that patients in these states report feeling emotions with an unusual intensity (Henry et al., 2007a, b,c). Classically, manic patients are considered to be more reactive to positive emotional stimuli, so they are more interested in pleasurable activities. However, this classic view of manic states is now challenged because most manic states display at least emotional lability and, most of the time, dysphoric features (Goodwin and Jamison, 2007). Dysphoric manic episodes have been shown to be associated with an elevated risk of suicidality (Goldberg et al., 1999). Therefore, manic episodes cannot be considered only as euphoric states where patients are consistently involved in pleasant activities. Functional brain imaging studies provide information about the mechanisms underlying this emotional reactivity. There have been very few functional magnetic resonance imaging (fMRI) studies of bipolar mania, likely due in part to the difficulty of scanning these subjects. However, most of the studies that used activation paradigms to target the amygdala, the main structure involved in emotional processes, have shown significantly increased activity in manic patients compared with healthy subjects (Chen, 2003; Altshuler et al., 2005). This overactivation could be due to a reduced VLPF (ventrolateral prefrontal cortex) regulation exerting an inhibitory action (Foland et al., 2008). Thus, brain-imaging may help in the identification of pathophysiological processes underlying abnormal emotional reactivity in manic episodes. To our knowledge, only one study has assessed the activation of the amygdala in manic patients as a function of the valence of the stimuli. Bermpohl et al. (2009) explored the response of the amygdala to affective stimuli in manic and healthy control subjects using slides extracted from the IAPS. Manic patients had a higher response in the left amygdala during the viewing of positive versus neutral slides. In that study, however, the pattern of response was the same for positive and negative slides in manic patients, even though the response was slightly lower for the latter. This lack of a significant
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difference could be due to the relatively small sample size (n = 10 subjects in each group). Our results also show that manic patients attribute a more pleasant valence to neutral slides. This suggests that they are more optimistic in the manner in which they perceive the environment when it is not perfectly codified. It does not mean, however, that they are less reactive to negative events. This pilot study adds more weight to the various sets of evidence (clinical, experimental and brain imaging) indicating that global emotional hyperreactivity is a characteristic of manic and mixed states. Amplification of the emotional response is involved in all types of stimulation. This amplified emotional response could represent the common characteristics of manic and mixed states (Lyon et al., 1999; Henry et al., 2003, Henry et al., 2007a,b,c; Elliott et al., 2004; Besnier et al., 2011). However, the difference could stem from the global tonality of affects, which are more positive in the first case and darker in mixed states. This investigation now needs to be performed in a larger group of patients to take into account the intensity of manic and depressive symptoms. Moreover, it would be pertinent to include objective components of the emotional response such as variations in skin conductance and heart rate, in order to obtain a plausible and exhaustive explanatory model of emotional hyperreactivity. However, recording these variables requires a large sample of patients since pharmaceutical treatments may confound the results. Our data also suggest that subjects in the manic and mixed groups regarded neutral slides in a more favorable light than control and euthymic bipolar patients. This in itself is a noteworthy finding, as it indicates that euphoria and irritability are not the only triggers in manic, hypomanic or mixed patients. These findings also show that neutral stimuli can trigger many emotions. Emotional reactivity is an efficient concept for clinicians because it can provide diagnostic assistance. Indeed, many manic, hypomanic and mixed patients cannot recognize themselves in the classical DSM-IV criteria (euphoria or irritability), and few patients complain about their emotional hyperreactivity when stimuli presented to them are positive or negative. The present findings might therefore help clinicians to improve their diagnostic procedure. They are also interesting for patients in that they provide better understanding of their own state and help them to recognize it as pathological. Role of funding source This work was funded by the “programme hospitalier de la recherche clinique” (PHRC, 2003). Katia M'bailara received a grant from the French Ministry of Research. Francesc Colom is grateful for the support and funding of the Spanish Ministry of Health, Instituto de Salud Carlos III, CIBER-SAM. Dr. Colom is also funded by the Spanish Ministry of Science and Innovation, Instituto Carlos III, through a “Miguel Servet” postdoctoral contract (CP08/00140) and a FIS (PS09/01044). Acknowledgments We received the support of the foundation FondaMental. References Altshuler, L., Bookheimer, S., Proenza, M.A., Townsend, J., Sabb, F., Firestine, A., Cohen, M.S., 2005. Increased amygdala activation during mania: a functional magnetic resonance imaging study. American Journal of Psychiatry 162, 1211–1213. Azorin, J.M., Hantouche, E.G., Akiskal, H.S., Bourgeois, M.L., Allilaire, J.F., Sechter, D., Châtenet-Duchêne, L., 2000. Structure factorielle du syndrome maniaque: revue de la littérature et résultats de l'étude française ‘EPIMAN’. Annales Médico-Psychologiques 158, 279–289. Bech, P., Rafaelsen, O.J., Kramp, P., Bolwig, T.G., 1978. The mania rating scale: scale construction and inter-observer agreement. Neuropharmacology 17, 430–431.
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