Letter to the Editor Received: February 23, 2015 Accepted after revision: September 10, 2015 Published online: November 27, 2015
Psychother Psychosom 2016;85:58–60 DOI: 10.1159/000441009
White Matter Plasticity Induced by Psychoeducation in Bipolar Patients: A Controlled Diffusion Tensor Imaging Study Pauline Favrea, Josselin Houenoub, c, Monica Baciua, Cédric Pichata, Cyril Poupond, Thierry Bougerole, f, Mircea Polosane, f a
LPNC, CNRS UMR 5105, Université Grenoble Alpes, Grenoble, UNIACT, Neurospin, I2BM, CEA Saclay, Gif-sur-Yvette, c AP-HP, Hôpitaux Universitaires Mondor, DHU PePsy, Fondation Fondamental, INSERM U955, Equipe 15, Pôle de Psychiatrie, Université Paris Est, Créteil, d UNIRS, Neurospin, I2BM, CEA Saclay, Gif-sur-Yvette, e CHU de Grenoble, Pôle Psychiatrie et Neurologie, Centre Expert en Troubles Bipolaires, Université Joseph Fourier, and f INSERM U836, GIN, CHU de Grenoble, Université Grenoble Alpes, Grenoble, France
b
Bipolar disorder (BD) is a severe mood disorder which is often difficult to treat. Pharmacological treatments are often effective in symptom management, but their effects are generally insufficient on a functional level [1]. Among psychosocial interventions, psychoeducation has recently shown significant and long-lasting effects on treatment adherence, relapse prevention and global functioning [2]. Consequently, psychoeducation is now positioned as an essential part of therapeutic strategies in BD, although its mechanistic neural action has not yet been precisely identified. The evidence for frontolimbic disconnectivity, responsible for emotional disturbance in BD, has been highlighted by functional magnetic resonance imaging (fMRI) [3, 4] as well as by diffusion tensor imaging (DTI) studies that reported abnormalities in white matter (WM) tracts linking frontal and limbic regions, such as the uncinate fasciculus [5]. However, to date, no study has investigated WM plasticity in patients with BD after a psychotherapeutic intervention, while dynamic changes in WM organization have been highlighted after various trainings in healthy subjects (HS),
Table 1. Demographic and clinical characteristics of BD patients and healthy subjects
Mean age ± SD, years Womena BD typea Type I Type II Other Mean age at the illness onset ± SD, years Mean duration of the illness ± SD, years Mean number of past depressive episodes ± SD Mean number of past manic episodes ± SD Mean number of past hypomanic episodes ± SD Positive history of psychotic episodesa Use of medicationa Without medication Lithium Anticonvulsants Antidepressants Antipsychotics
SUP group (n = 12)
CTL group (n = 12)
Differences between variables (d.f.)
p value
44.42 ± 8.35 66.67%
46.00 ± 10.48 33.33%
43.58 ± 11.18 66.67
0.19 (2, 33) 1.83 (2, 33)
0.83 0.18
33.33% 41.67% 17.67% 28.50 ± 8.85 16.92 ± 11.16 4.29 ± 3.73 1.57 ± 1.51 4.33 ± 3.39 41.67 ± 51.49
27.27% 45.45% 27.27% 28.30 ± 7.96 18.60 ± 10.67 6.63 ± 7.09 1.71 ± 2.98 3.13 ± 3.98 45.45 ± 52.22
0.14 (1) 0.09 (1) 0.20 (1) 0.05 (20) 0.36 (20) 0.78 (13) 0.11 (12) 0.60 (12) 0.17 (21)
0.70 0.76 0.65 0.96 0.72 0.44 0.91 0.56 0.86
16.67% 58.33% 41.67% 16.67% 8.33%
18.18% 36.36% 27.27% 27.27% 9.09%
0.00 (1) 0.82 (1) 0.50 (1) 0.20 (1) 0.00 (1)
1.00 0.37 0.48 0.65 1.00
variables calculated as number (percentage) of patients. Percentages have been rounded and may not total.
© 2015 S. Karger AG, Basel 0033–3190/15/0851–0058$39.50/0 E-Mail [email protected] www.karger.com/pps
Pauline Favre Deptartment of Social Neuroscience Max Planck Institute for Human Cognitive and Brain Sciences Stephanstrasse 1A, DE–04103 Leipzig (Germany) E-Mail favre @ cbs.mpg.de
Downloaded by: UCONN Storrs 198.143.38.1 - 2/2/2016 7:06:39 PM
a Caterorical
PED group (n = 12)
Data are reported as mean (SD). Bold values highlight significant results. NA = Not applicable. a Values were multiplied by 102 to improve readability. b Values were multiplied by 1010 to improve readability.
0.00 0.03 0.01 (1, 9) 0.92 0.27 (1, 9) 0.61 9.03 (0.85) 9.43 (0.83) 9.06 (0.93) 9.25 (0.93) 0.07 0.05 0.45 0.53 8.95 (0.09) 9.39 (0.54) 0.01 0.00 0.58 0.97 0.31 (1, 33) 0.00 (1, 33)
0.02 0.00 0.63 (1, 33) 0.10 (1, 33)
0.43 0.76
p value F (d.f.) CTL
9.23 (1.02) 9.24 (0.56) 9.00 (0.91) 8.74 (0.72) 9.32 (0.56) 9.33 (0.39) Right uncinate GFAa MDb
0.63 (1, 9) 0.43 (1, 9)
0.05 0.01 0.41 (1, 9) 0.54 0.09 (1, 9) 0.77 9.14 (0.96) 9.28 (0.63) 9.00 (0.87) 9.12 (0.77) 0.24 0.42 8.96 (1.00) 9.66 (1.38) 9.24 (0.49) 8.98 (0.58) 8.99 (0.92) 8.65 (0.66) 9.18 (0.63) 9.31 (0.58) Left uncinate GFAa MDb
2.83 (1, 9) 0.13 6.52 (1, 9) 0.03
NA NA NA 0.34 0.72 0.21 10.00 (8.87) 12.58 (9.50) –0.98 (11) 2.58 (3.23) 3.17 (4.45) –0.36 (11) 65.80 (9.95) 70.60 (7.62) –1.34 (9) 0.048 NA 0.74 NA 2*SD). The decrease of the MD within the left uncinate fasciculus after the psychoeducation suggests beneficial effects of psychoeducation on frontolimbic tracts. Since higher levels of MD are associated with myelin damage, a possible explanation for the observed MD change in our study is increased myelination after psychoeducation [11]. BD symptoms may be subtended by the inability of
Acknowledgments This work has been supported by research grants from the Grenoble University Hospital, the French University Institute, the Grenoble Cognition Center, and the Health and Society Research Network of the Pierre Mendès-France University (Grenoble). The
60
Psychother Psychosom 2016;85:58–60 DOI: 10.1159/000441009
Grenoble MRI facility IRMaGE was partly funded by the French program Investissements d’avenir run by the Agence Nationale pour la Recherche; grant Infrastructure d’avenir en Biologie Santé – ANR-11-INBS-0006. Disclosure Statement The authors declare that there is no conflict of interest or external financial support with regard to this article.
References 1 Huxley N, Baldessarini RJ: Disability and its treatment in bipolar disorder patients. Bipolar Disord 2007;9:183–196. 2 Colom F, Vieta E, Sánchez-Moreno J, Goikolea JM, Popova E, Bonnin CM, Scott J: Psychoeducation for bipolar II disorder: an exploratory, 5-year outcome subanalysis. J Affect Disord 2009;112:30–35. 3 Favre P, Baciu M, Pichat C, Bougerol T, Polosan M: fMRI evidence for abnormal resting-state functional connectivity in euthymic bipolar patients. J Affect Disord 2014;165:182–189. 4 Townsend JD, Torrisi SJ, Lieberman MD, Sugar CA, Bookheimer SY, Altshuler LL: Frontal-amygdala connectivity alterations during emotion downregulation in bipolar I disorder. Biol Psychiatry 2013;73:127–135. 5 Houenou J, Wessa M, Douaud G, Leboyer M, Chanraud S, Perrin M, Poupon C, Martinot JL, Paillere-Martinot ML: Increased white matter connectivity in euthymic bipolar patients: diffusion tensor tractography between the subgenual cingulate and the amygdalo-hippocampal complex. Mol Psychiatry 2007;12:1001–1010. 6 Tang YY, Lu Q, Geng X, Stein EA, Yang Y, Posner MI: Short-term meditation induces white matter changes in the anterior cingulate. Proc Natl Acad Sci 2010;107:15649–15652. 7 Scholz J, Klein MC, Behrens TEJ, Johansen-Berg H: Training induces changes in white-matter architecture. Nat Neurosci 2009;12:1370–1371. 8 Takeuchi H, Sekiguchi A, Taki Y, Yokoyama S, Yomogida Y, Komuro N, Yamanouchi T, Suzuki S, Kawashima R: Training of working memory impacts structural connectivity. J Neurosci 2010;30:3297–3303. 9 Favre P, Baciu M, Pichat C, De Pourtalès M-A, Fredembach B, Garçon S, Bougerol T, Polosan M: Modulation of fronto-limbic activity by the psychoeducation in euthymic bipolar patients. A functional MRI study. Psychiatry Res Neuroimaging 2013;214:285–295. 10 Sarrazin S, Poupon C, Linke J, Wessa M, Phillips M, Delavest M, Versace A, Almeida J, Guevara P, Duclap D, Duchesnay E, Mangin J-F, Le Dual K, Daban C, Hamdani N, D’Albis M-A, Leboyer M, Houenou J: A multicenter tractography study of deep white matter tracts in bipolar I disorder: psychotic features and interhemispheric disconnectivity. JAMA Psychiatry 2014;71:388. 11 Zatorre RJ, Fields RD, Johansen-Berg H: Plasticity in gray and white: neuroimaging changes in brain structure during learning. Nat Neurosci 2012;15:528–536.
Favre/Houenou/Baciu/Pichat/Poupon/ Bougerol/Polosan
Downloaded by: UCONN Storrs 198.143.38.1 - 2/2/2016 7:06:39 PM
prefrontal areas to modulate the limbic hyperreactivity because of abnormal prefrontolimbic connectivity in BD patients. The present results together with those of our previous fMRI study, in which we demonstrated in a different sample of BD patients decreased activity in the hippocampus and increased activity within the inferior frontal gyrus after the psychoeducation when processing a word-face emotional Stroop task [9], suggest that psychoeducation may help patients to better manage their disorder by improving the cognitive control over their emotions through a better prefrontolimbic anatomical connectivity. Indeed, in psychoeducation programs, patients are taught to identify consciously their symptoms and to adopt coping strategies focused on problem solving and social support seeking rather than emotional avoidance. Specific benefits for depressive residual symptoms and functioning have also been noticed in the PED group versus the SUP group. Some limitations have to be mentioned. First, as mentioned previously, the sample size of our study is modest. Therefore, the generalization of our results may be compromised. However, longitudinal designs increase the statistical power of studies by removing the interindividual variability. Second, the BD patients were scanned right after the end of psychoeducation. It would be interesting to assess whether the effects are long-lasting and whether other effects appear in the longer term. Lastly, measures of GFA and MD were averages over the entire bundle. In the future, it might be interesting to look at the profiles of these measures to increase the specificity of the localization of the modifications occurring along the bundle. This first randomized controlled longitudinal DTI study aims at investigating microstructural WM changes in patients with BD after psychoeducation or nonstructured support group intervention. We showed that only BD patients who underwent the psychoeducation present a decrease in MD along the left uncinate fasciculus. This result highlights changes of the structural organization of the brain after a structured therapeutic intervention, such as psychoeducation, which may putatively be linked to the improvement of emotional regulation after the psychoeducation. Future studies with larger sample size are warranted to assess longterm effects of psychoeducation on cerebral networks.
Psychother Psychosom 2016;85:58–60 DOI: 10.1159/000441009
White Matter Plasticity Induced by Psychoeducation in Bipolar Patients: A Controlled Diffusion Tensor Imaging Study Pauline Favrea, Josselin Houenoub, c, Monica Baciua, Cédric Pichata, Cyril Poupond, Thierry Bougerole, f, Mircea Polosane, f a
LPNC, CNRS UMR 5105, Université Grenoble Alpes, Grenoble, UNIACT, Neurospin, I2BM, CEA Saclay, Gif-sur-Yvette, c AP-HP, Hôpitaux Universitaires Mondor, DHU PePsy, Fondation Fondamental, INSERM U955, Equipe 15, Pôle de Psychiatrie, Université Paris Est, Créteil, d UNIRS, Neurospin, I2BM, CEA Saclay, Gif-sur-Yvette, e CHU de Grenoble, Pôle Psychiatrie et Neurologie, Centre Expert en Troubles Bipolaires, Université Joseph Fourier, and f INSERM U836, GIN, CHU de Grenoble, Université Grenoble Alpes, Grenoble, France
b
Bipolar disorder (BD) is a severe mood disorder which is often difficult to treat. Pharmacological treatments are often effective in symptom management, but their effects are generally insufficient on a functional level [1]. Among psychosocial interventions, psychoeducation has recently shown significant and long-lasting effects on treatment adherence, relapse prevention and global functioning [2]. Consequently, psychoeducation is now positioned as an essential part of therapeutic strategies in BD, although its mechanistic neural action has not yet been precisely identified. The evidence for frontolimbic disconnectivity, responsible for emotional disturbance in BD, has been highlighted by functional magnetic resonance imaging (fMRI) [3, 4] as well as by diffusion tensor imaging (DTI) studies that reported abnormalities in white matter (WM) tracts linking frontal and limbic regions, such as the uncinate fasciculus [5]. However, to date, no study has investigated WM plasticity in patients with BD after a psychotherapeutic intervention, while dynamic changes in WM organization have been highlighted after various trainings in healthy subjects (HS),
Table 1. Demographic and clinical characteristics of BD patients and healthy subjects
Mean age ± SD, years Womena BD typea Type I Type II Other Mean age at the illness onset ± SD, years Mean duration of the illness ± SD, years Mean number of past depressive episodes ± SD Mean number of past manic episodes ± SD Mean number of past hypomanic episodes ± SD Positive history of psychotic episodesa Use of medicationa Without medication Lithium Anticonvulsants Antidepressants Antipsychotics
SUP group (n = 12)
CTL group (n = 12)
Differences between variables (d.f.)
p value
44.42 ± 8.35 66.67%
46.00 ± 10.48 33.33%
43.58 ± 11.18 66.67
0.19 (2, 33) 1.83 (2, 33)
0.83 0.18
33.33% 41.67% 17.67% 28.50 ± 8.85 16.92 ± 11.16 4.29 ± 3.73 1.57 ± 1.51 4.33 ± 3.39 41.67 ± 51.49
27.27% 45.45% 27.27% 28.30 ± 7.96 18.60 ± 10.67 6.63 ± 7.09 1.71 ± 2.98 3.13 ± 3.98 45.45 ± 52.22
0.14 (1) 0.09 (1) 0.20 (1) 0.05 (20) 0.36 (20) 0.78 (13) 0.11 (12) 0.60 (12) 0.17 (21)
0.70 0.76 0.65 0.96 0.72 0.44 0.91 0.56 0.86
16.67% 58.33% 41.67% 16.67% 8.33%
18.18% 36.36% 27.27% 27.27% 9.09%
0.00 (1) 0.82 (1) 0.50 (1) 0.20 (1) 0.00 (1)
1.00 0.37 0.48 0.65 1.00
variables calculated as number (percentage) of patients. Percentages have been rounded and may not total.
© 2015 S. Karger AG, Basel 0033–3190/15/0851–0058$39.50/0 E-Mail [email protected] www.karger.com/pps
Pauline Favre Deptartment of Social Neuroscience Max Planck Institute for Human Cognitive and Brain Sciences Stephanstrasse 1A, DE–04103 Leipzig (Germany) E-Mail favre @ cbs.mpg.de
Downloaded by: UCONN Storrs 198.143.38.1 - 2/2/2016 7:06:39 PM
a Caterorical
PED group (n = 12)
Data are reported as mean (SD). Bold values highlight significant results. NA = Not applicable. a Values were multiplied by 102 to improve readability. b Values were multiplied by 1010 to improve readability.
0.00 0.03 0.01 (1, 9) 0.92 0.27 (1, 9) 0.61 9.03 (0.85) 9.43 (0.83) 9.06 (0.93) 9.25 (0.93) 0.07 0.05 0.45 0.53 8.95 (0.09) 9.39 (0.54) 0.01 0.00 0.58 0.97 0.31 (1, 33) 0.00 (1, 33)
0.02 0.00 0.63 (1, 33) 0.10 (1, 33)
0.43 0.76
p value F (d.f.) CTL
9.23 (1.02) 9.24 (0.56) 9.00 (0.91) 8.74 (0.72) 9.32 (0.56) 9.33 (0.39) Right uncinate GFAa MDb
0.63 (1, 9) 0.43 (1, 9)
0.05 0.01 0.41 (1, 9) 0.54 0.09 (1, 9) 0.77 9.14 (0.96) 9.28 (0.63) 9.00 (0.87) 9.12 (0.77) 0.24 0.42 8.96 (1.00) 9.66 (1.38) 9.24 (0.49) 8.98 (0.58) 8.99 (0.92) 8.65 (0.66) 9.18 (0.63) 9.31 (0.58) Left uncinate GFAa MDb
2.83 (1, 9) 0.13 6.52 (1, 9) 0.03
NA NA NA 0.34 0.72 0.21 10.00 (8.87) 12.58 (9.50) –0.98 (11) 2.58 (3.23) 3.17 (4.45) –0.36 (11) 65.80 (9.95) 70.60 (7.62) –1.34 (9) 0.048 NA 0.74 NA 2*SD). The decrease of the MD within the left uncinate fasciculus after the psychoeducation suggests beneficial effects of psychoeducation on frontolimbic tracts. Since higher levels of MD are associated with myelin damage, a possible explanation for the observed MD change in our study is increased myelination after psychoeducation [11]. BD symptoms may be subtended by the inability of
Acknowledgments This work has been supported by research grants from the Grenoble University Hospital, the French University Institute, the Grenoble Cognition Center, and the Health and Society Research Network of the Pierre Mendès-France University (Grenoble). The
60
Psychother Psychosom 2016;85:58–60 DOI: 10.1159/000441009
Grenoble MRI facility IRMaGE was partly funded by the French program Investissements d’avenir run by the Agence Nationale pour la Recherche; grant Infrastructure d’avenir en Biologie Santé – ANR-11-INBS-0006. Disclosure Statement The authors declare that there is no conflict of interest or external financial support with regard to this article.
References 1 Huxley N, Baldessarini RJ: Disability and its treatment in bipolar disorder patients. Bipolar Disord 2007;9:183–196. 2 Colom F, Vieta E, Sánchez-Moreno J, Goikolea JM, Popova E, Bonnin CM, Scott J: Psychoeducation for bipolar II disorder: an exploratory, 5-year outcome subanalysis. J Affect Disord 2009;112:30–35. 3 Favre P, Baciu M, Pichat C, Bougerol T, Polosan M: fMRI evidence for abnormal resting-state functional connectivity in euthymic bipolar patients. J Affect Disord 2014;165:182–189. 4 Townsend JD, Torrisi SJ, Lieberman MD, Sugar CA, Bookheimer SY, Altshuler LL: Frontal-amygdala connectivity alterations during emotion downregulation in bipolar I disorder. Biol Psychiatry 2013;73:127–135. 5 Houenou J, Wessa M, Douaud G, Leboyer M, Chanraud S, Perrin M, Poupon C, Martinot JL, Paillere-Martinot ML: Increased white matter connectivity in euthymic bipolar patients: diffusion tensor tractography between the subgenual cingulate and the amygdalo-hippocampal complex. Mol Psychiatry 2007;12:1001–1010. 6 Tang YY, Lu Q, Geng X, Stein EA, Yang Y, Posner MI: Short-term meditation induces white matter changes in the anterior cingulate. Proc Natl Acad Sci 2010;107:15649–15652. 7 Scholz J, Klein MC, Behrens TEJ, Johansen-Berg H: Training induces changes in white-matter architecture. Nat Neurosci 2009;12:1370–1371. 8 Takeuchi H, Sekiguchi A, Taki Y, Yokoyama S, Yomogida Y, Komuro N, Yamanouchi T, Suzuki S, Kawashima R: Training of working memory impacts structural connectivity. J Neurosci 2010;30:3297–3303. 9 Favre P, Baciu M, Pichat C, De Pourtalès M-A, Fredembach B, Garçon S, Bougerol T, Polosan M: Modulation of fronto-limbic activity by the psychoeducation in euthymic bipolar patients. A functional MRI study. Psychiatry Res Neuroimaging 2013;214:285–295. 10 Sarrazin S, Poupon C, Linke J, Wessa M, Phillips M, Delavest M, Versace A, Almeida J, Guevara P, Duclap D, Duchesnay E, Mangin J-F, Le Dual K, Daban C, Hamdani N, D’Albis M-A, Leboyer M, Houenou J: A multicenter tractography study of deep white matter tracts in bipolar I disorder: psychotic features and interhemispheric disconnectivity. JAMA Psychiatry 2014;71:388. 11 Zatorre RJ, Fields RD, Johansen-Berg H: Plasticity in gray and white: neuroimaging changes in brain structure during learning. Nat Neurosci 2012;15:528–536.
Favre/Houenou/Baciu/Pichat/Poupon/ Bougerol/Polosan
Downloaded by: UCONN Storrs 198.143.38.1 - 2/2/2016 7:06:39 PM
prefrontal areas to modulate the limbic hyperreactivity because of abnormal prefrontolimbic connectivity in BD patients. The present results together with those of our previous fMRI study, in which we demonstrated in a different sample of BD patients decreased activity in the hippocampus and increased activity within the inferior frontal gyrus after the psychoeducation when processing a word-face emotional Stroop task [9], suggest that psychoeducation may help patients to better manage their disorder by improving the cognitive control over their emotions through a better prefrontolimbic anatomical connectivity. Indeed, in psychoeducation programs, patients are taught to identify consciously their symptoms and to adopt coping strategies focused on problem solving and social support seeking rather than emotional avoidance. Specific benefits for depressive residual symptoms and functioning have also been noticed in the PED group versus the SUP group. Some limitations have to be mentioned. First, as mentioned previously, the sample size of our study is modest. Therefore, the generalization of our results may be compromised. However, longitudinal designs increase the statistical power of studies by removing the interindividual variability. Second, the BD patients were scanned right after the end of psychoeducation. It would be interesting to assess whether the effects are long-lasting and whether other effects appear in the longer term. Lastly, measures of GFA and MD were averages over the entire bundle. In the future, it might be interesting to look at the profiles of these measures to increase the specificity of the localization of the modifications occurring along the bundle. This first randomized controlled longitudinal DTI study aims at investigating microstructural WM changes in patients with BD after psychoeducation or nonstructured support group intervention. We showed that only BD patients who underwent the psychoeducation present a decrease in MD along the left uncinate fasciculus. This result highlights changes of the structural organization of the brain after a structured therapeutic intervention, such as psychoeducation, which may putatively be linked to the improvement of emotional regulation after the psychoeducation. Future studies with larger sample size are warranted to assess longterm effects of psychoeducation on cerebral networks.
