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1. White matter microstructure and its relation to clinical features of obsessive–compulsive disorder: findings from the ENIGMA OCD Working Group

Author

Piras F., Abe Y., Agarwal S. M., Anticevic A., Ameis S., Arnold P., Banaj N., Bargallo N., Batistuzzo M. C., Benedetti F., Beucke J. -C., Boedhoe P. S. W., Bollettini I., Brem S., Calvo A., Cho K. I. K., Ciullo V., Dallaspezia S., Dickie E., Ely B. A., Fan S., Fouche J. -P., Gruner P., Gursel D. A., Hauser T., Hirano Y., Hoexter M. Q., Iorio M., James A., Reddy Y. C. J., Kaufmann C., Koch K., Kochunov P., Kwon J. S., Lazaro L., Lochner C., Marsh R., Nakagawa A., Nakamae T., Narayanaswamy J. C., Sakai Y., Shimizu E., Simon D., Simpson H. B., Soreni N., Stampfli P., Stern E. R., Szeszko P., Takahashi J., Venkatasubramanian G., Wang Z., Yun J. -Y., Assogna F., Calvo R., Wit S. J., Hough M., Kuno M., Miguel E. C., Morer A., Pittenger C., Poletti S., Smeraldi E., Sato J. R., Tsuchiyagaito A., Walitza S., van der Werf Y. D., Vecchio D., Zarei M., Stein D. J., Jahanshad N., Thompson P. M., van den Heuvel O. A., Spalletta G., Piras, F., Abe, Y., Agarwal, S. M., Anticevic, A., Ameis, S., Arnold, P., Banaj, N., Bargallo, N., Batistuzzo, M. C., Benedetti, F., Beucke, J. -C., Boedhoe, P. S. W., Bollettini, I., Brem, S., Calvo, A., Cho, K. I. K., Ciullo, V., Dallaspezia, S., Dickie, E., Ely, B. A., Fan, S., Fouche, J. -P., Gruner, P., Gursel, D. A., Hauser, T., Hirano, Y., Hoexter, M. Q., Iorio, M., James, A., Reddy, Y. C. J., Kaufmann, C., Koch, K., Kochunov, P., Kwon, J. S., Lazaro, L., Lochner, C., Marsh, R., Nakagawa, A., Nakamae, T., Narayanaswamy, J. C., Sakai, Y., Shimizu, E., Simon, D., Simpson, H. B., Soreni, N., Stampfli, P., Stern, E. R., Szeszko, P., Takahashi, J., Venkatasubramanian, G., Wang, Z., Yun, J. -Y., Assogna, F., Calvo, R., Wit, S. J., Hough, M., Kuno, M., Miguel, E. C., Morer, A., Pittenger, C., Poletti, S., Smeraldi, E., Sato, J. R., Tsuchiyagaito, A., Walitza, S., van der Werf, Y. D., Vecchio, D., Zarei, M., Stein, D. J., Jahanshad, N., Thompson, P. M., van den Heuvel, O. A., Spalletta, G., Anatomy and neurosciences, Psychiatry, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, and Amsterdam Neuroscience - Neurodegeneration

Subjects
Adult, Obsessive-Compulsive Disorder, medicine.medical_specialty, Younger age, Cross-sectional study, Article, lcsh:RC321-571, White matter, neuroscience, Cellular and Molecular Neuroscience, Group differences, Obsessive compulsive, Internal medicine, Fractional anisotropy, medicine, Humans, 100 Philosophie und Psychologie::150 Psychologie::150 Psychologie, Child, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, business.industry, Brain, White Matter, White matter microstructure, obsessive-compulsive disorder, Psychiatry and Mental health, Cross-Sectional Studies, Diffusion Magnetic Resonance Imaging, Diffusion Tensor Imaging, medicine.anatomical_structure, psychiatric disorders, Anisotropy, business, Diffusion MRI
Abstract

Microstructural alterations in cortico-subcortical connections are thought to be present in obsessive–compulsive disorder (OCD). However, prior studies have yielded inconsistent findings, perhaps because small sample sizes provided insufficient power to detect subtle abnormalities. Here we investigated microstructural white matter alterations and their relation to clinical features in the largest dataset of adult and pediatric OCD to date. We analyzed diffusion tensor imaging metrics from 700 adult patients and 645 adult controls, as well as 174 pediatric patients and 144 pediatric controls across 19 sites participating in the ENIGMA OCD Working Group, in a cross-sectional case-control magnetic resonance study. We extracted measures of fractional anisotropy (FA) as main outcome, and mean diffusivity, radial diffusivity, and axial diffusivity as secondary outcomes for 25 white matter regions. We meta-analyzed patient-control group differences (Cohen’s d) across sites, after adjusting for age and sex, and investigated associations with clinical characteristics. Adult OCD patients showed significant FA reduction in the sagittal stratum (d = −0.21, z = −3.21, p = 0.001) and posterior thalamic radiation (d = −0.26, z = −4.57, p z = 2.71, p = 0.006), longer duration of illness (z = −2.086, p = 0.036), and a higher percentage of medicated patients in the cohorts studied (z = −1.98, p = 0.047). No significant association with symptom severity was found. Pediatric OCD patients did not show any detectable microstructural abnormalities compared to controls. Our findings of microstructural alterations in projection and association fibers to posterior brain regions in OCD are consistent with models emphasizing deficits in connectivity as an important feature of this disorder.

Published
2021
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4. Variations in seasonal solar insolation are associated with a history of suicide attempts in bipolar I disorder

Author

Bauer, M. Glenn, T. Achtyes, E.D. Alda, M. Agaoglu, E. Altınbaş, K. Andreassen, O.A. Angelopoulos, E. Ardau, R. Vares, E.A. Aydin, M. Ayhan, Y. Baethge, C. Bauer, R. Baune, B.T. Balaban, C. Becerra-Palars, C. Behere, A.P. Behere, P.B. Belete, H. Belete, T. Belizario, G.O. Bellivier, F. Belmaker, R.H. Benedetti, F. Berk, M. Bersudsky, Y. Bicakci, Ş. Birabwa-Oketcho, H. Bjella, T.D. Brady, C. Cabrera, J. Cappucciati, M. Castro, A.M.P. Chen, W.-L. Cheung, E.Y.W. Chiesa, S. Crowe, M. Cuomo, A. Dallaspezia, S. Del Zompo, M. Desai, P. Dodd, S. Donix, M. Etain, B. Fagiolini, A. Fellendorf, F.T. Ferensztajn-Rochowiak, E. Fiedorowicz, J.G. Fountoulakis, K.N. Frye, M.A. Geoffroy, P.A. Gonzalez-Pinto, A. Gottlieb, J.F. Grof, P. Haarman, B.C.M. Harima, H. Hasse-Sousa, M. Henry, C. Høffding, L. Houenou, J. Imbesi, M. Isometsä, E.T. Ivkovic, M. Janno, S. Johnsen, S. Kapczinski, F. Karakatsoulis, G.N. Kardell, M. Kessing, L.V. Kim, S.J. König, B. Kot, T.L. Koval, M. Kunz, M. Lafer, B. Landén, M. Larsen, E.R. Lenger, M. Lewitzka, U. Licht, R.W. Lopez-Jaramillo, C. MacKenzie, A. Madsen, H.Ø. Madsen, S.A.K.A. Mahadevan, J. Mahardika, A. Manchia, M. Marsh, W. Martinez-Cengotitabengoa, M. Martiny, K. Mashima, Y. McLoughlin, D.M. Meesters, Y. Melle, I. Meza-Urzúa, F. Ming, M.Y. Monteith, S. Moorthy, M. Morken, G. Mosca, E. Mozzhegorov, A.A. Munoz, R. Mythri, S.V. Nacef, F. Nadella, R.K. Nakanotani, T. Nielsen, R.E. O‘Donovan, C. Omrani, A. Osher, Y. Ouali, U. Pantovic-Stefanovic, M. Pariwatcharakul, P. Petite, J. Pfennig, A. Ruiz, Y.P. Pilhatsch, M. Pinna, M. Pompili, M. Porter, R. Quiroz, D. Rabelo-da-Ponte, F.D. Ramesar, R. Rasgon, N. Ratta-apha, W. Ratzenhofer, M. Redahan, M. Reddy, M.S. Reif, A. Reininghaus, E.Z. Richards, J.G. Ritter, P. Rybakowski, J.K. Sathyaputri, L. Scippa, Â.M. Simhandl, C. Severus, E. Smith, D. Smith, J. Stackhouse, P.W., Jr. Stein, D.J. Stilwell, K. Strejilevich, S. Su, K.-P. Subramaniam, M. Sulaiman, A.H. Suominen, K. Tanra, A.J. Tatebayashi, Y. Teh, W.L. Tondo, L. Torrent, C. Tuinstra, D. Uchida, T. Vaaler, A.E. Veeh, J. Vieta, E. Viswanath, B. Yoldi-Negrete, M. Yalcinkaya, O.K. Young, A.H. Zgueb, Y. Whybrow, P.C.

Abstract

Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed. © 2021, The Author(s).

Published
2021

5. Variations in seasonal solar insolation are associated with a history of suicide attempts in bipolar I disorder

Author

Bauer, M, Glenn, T, Achtyes, ED, Alda, M, Agaoglu, E, Altınbaş, K, Andreassen, OA, Angelopoulos, E, Ardau, R, Vares, EA, Aydin, M, Ayhan, Y, Baethge, C, Bauer, R, Baune, BT, Balaban, C, Becerra-Palars, C, Behere, AP, Behere, PB, Belete, H, Belete, T, Belizario, GO, Bellivier, F, Belmaker, RH, Benedetti, F, Berk, Michael, Bersudsky, Y, Bicakci, Ş, Birabwa-Oketcho, H, Bjella, TD, Brady, C, Cabrera, J, Cappucciati, M, Castro, AMP, Chen, WL, Cheung, EYW, Chiesa, S, Crowe, M, Cuomo, A, Dallaspezia, S, Del Zompo, M, Desai, P, Dodd, Seetal, Donix, M, Etain, B, Fagiolini, A, Fellendorf, FT, Ferensztajn-Rochowiak, E, Fiedorowicz, JG, Fountoulakis, KN, Frye, MA, Geoffroy, PA, Gonzalez-Pinto, A, Gottlieb, JF, Grof, P, Haarman, BCM, Harima, H, Hasse-Sousa, M, Henry, C, Høffding, L, Houenou, J, Imbesi, M, Isometsä, ET, Ivkovic, M, Janno, S, Johnsen, S, Kapczinski, F, Karakatsoulis, GN, Kardell, M, Kessing, LV, Kim, SJ, König, B, Kot, TL, Koval, M, Kunz, M, Lafer, B, Landén, M, Larsen, ER, Lenger, M, Lewitzka, U, Licht, RW, Lopez-Jaramillo, C, MacKenzie, A, Madsen, HØ, Madsen, SAKA, Mahadevan, J, Mahardika, A, Manchia, M, Marsh, W, Martinez-Cengotitabengoa, M, Martiny, K, Mashima, Y, McLoughlin, DM, Meesters, Y, Melle, I, Meza-Urzúa, F, Ming, MY, Monteith, S, Moorthy, M, Morken, G, Bauer, M, Glenn, T, Achtyes, ED, Alda, M, Agaoglu, E, Altınbaş, K, Andreassen, OA, Angelopoulos, E, Ardau, R, Vares, EA, Aydin, M, Ayhan, Y, Baethge, C, Bauer, R, Baune, BT, Balaban, C, Becerra-Palars, C, Behere, AP, Behere, PB, Belete, H, Belete, T, Belizario, GO, Bellivier, F, Belmaker, RH, Benedetti, F, Berk, Michael, Bersudsky, Y, Bicakci, Ş, Birabwa-Oketcho, H, Bjella, TD, Brady, C, Cabrera, J, Cappucciati, M, Castro, AMP, Chen, WL, Cheung, EYW, Chiesa, S, Crowe, M, Cuomo, A, Dallaspezia, S, Del Zompo, M, Desai, P, Dodd, Seetal, Donix, M, Etain, B, Fagiolini, A, Fellendorf, FT, Ferensztajn-Rochowiak, E, Fiedorowicz, JG, Fountoulakis, KN, Frye, MA, Geoffroy, PA, Gonzalez-Pinto, A, Gottlieb, JF, Grof, P, Haarman, BCM, Harima, H, Hasse-Sousa, M, Henry, C, Høffding, L, Houenou, J, Imbesi, M, Isometsä, ET, Ivkovic, M, Janno, S, Johnsen, S, Kapczinski, F, Karakatsoulis, GN, Kardell, M, Kessing, LV, Kim, SJ, König, B, Kot, TL, Koval, M, Kunz, M, Lafer, B, Landén, M, Larsen, ER, Lenger, M, Lewitzka, U, Licht, RW, Lopez-Jaramillo, C, MacKenzie, A, Madsen, HØ, Madsen, SAKA, Mahadevan, J, Mahardika, A, Manchia, M, Marsh, W, Martinez-Cengotitabengoa, M, Martiny, K, Mashima, Y, McLoughlin, DM, Meesters, Y, Melle, I, Meza-Urzúa, F, Ming, MY, Monteith, S, Moorthy, M, and Morken, G

Abstract

Abstract Background Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, a

Published
2021

7. Subcortical brain volume, regional cortical thickness, and cortical surface area across disorders: Findings from the ENIGMA ADHD, ASD, and OCD Working Groups

Author

Boedhoe, P.S., Rooij, D. van, Hoogman, M., Twisk, J.W.R., Schmaal, L., Abe, Y., Alonso, P., Ameis, S.H., Anikin, A., Anticevic, A., Arango, C., Arnold, P.D., Asherson, P., Assogna, F., Auzias, G., Banaschewski, T., Baranov, A., Batistuzzo, M.C., Baumeister, S., Baur-Streubel, R., Behrmann, M., Bellgrove, M.A., Benedetti, F. De, Beucke, J.C., Biederman, J., Bollettini, I., Bose, A., Bralten, J., Bramati, I.E., Brandeis, D., Brem, S., Brennan, B.P., Busatto, G.F., Calderoni, S., Calvo, A., Calvo, R., Castellanos, F.X., Cercignani, M., Chaim-Avancini, T.M., Chantiluke, K.C., Cheng, Y., Cho, K.I.K., Christakou, A., Coghill, D., Conzelmann, A., Cubillo, A.I., Dale, A.M., Dallaspezia, S., Daly, E., Denys, D., Deruelle, C., Martino, A, Dinstein, I., Doyle, A.E., Durston, S., Earl, E.A., Ecker, C., Ehrlich, S., Ely, B.A., Epstein, J.N., Ethofer, T., Fair, D.A., Fallgatter, A.J., Faraone, S.V, Fedor, J., Feng, X., Feusner, J.D., Fitzgerald, J., Fitzgerald, K.D., Fouche, J.P., Freitag, C.M., Fridgeirsson, E.A., Frodl, T., Gabel, M.C., Gallagher, L., Gogberashvili, T., Gori, I., Gruner, P., Gürsel, D.A., Haar, S., Haavik, J., Hall, G.B., Harrison, N.A., Hartman, Catharina A., Heslenfeld, D.J., Hirano, Y., Hoekstra, P.J., Hoexter, M.Q., Hohmann, S., Høvik, M.F., Hu, H., Huyser, C., Jahanshad, N., Jalbrzikowski, M., James, A., Janssen, J, Jaspers-Fayer, F., Jernigan, T.L., Kapilushniy, D., Kardatzki, B., Buitelaar, J.K., Franke, B., Heuvel, O.A. van den, Boedhoe, P.S., Rooij, D. van, Hoogman, M., Twisk, J.W.R., Schmaal, L., Abe, Y., Alonso, P., Ameis, S.H., Anikin, A., Anticevic, A., Arango, C., Arnold, P.D., Asherson, P., Assogna, F., Auzias, G., Banaschewski, T., Baranov, A., Batistuzzo, M.C., Baumeister, S., Baur-Streubel, R., Behrmann, M., Bellgrove, M.A., Benedetti, F. De, Beucke, J.C., Biederman, J., Bollettini, I., Bose, A., Bralten, J., Bramati, I.E., Brandeis, D., Brem, S., Brennan, B.P., Busatto, G.F., Calderoni, S., Calvo, A., Calvo, R., Castellanos, F.X., Cercignani, M., Chaim-Avancini, T.M., Chantiluke, K.C., Cheng, Y., Cho, K.I.K., Christakou, A., Coghill, D., Conzelmann, A., Cubillo, A.I., Dale, A.M., Dallaspezia, S., Daly, E., Denys, D., Deruelle, C., Martino, A, Dinstein, I., Doyle, A.E., Durston, S., Earl, E.A., Ecker, C., Ehrlich, S., Ely, B.A., Epstein, J.N., Ethofer, T., Fair, D.A., Fallgatter, A.J., Faraone, S.V, Fedor, J., Feng, X., Feusner, J.D., Fitzgerald, J., Fitzgerald, K.D., Fouche, J.P., Freitag, C.M., Fridgeirsson, E.A., Frodl, T., Gabel, M.C., Gallagher, L., Gogberashvili, T., Gori, I., Gruner, P., Gürsel, D.A., Haar, S., Haavik, J., Hall, G.B., Harrison, N.A., Hartman, Catharina A., Heslenfeld, D.J., Hirano, Y., Hoekstra, P.J., Hoexter, M.Q., Hohmann, S., Høvik, M.F., Hu, H., Huyser, C., Jahanshad, N., Jalbrzikowski, M., James, A., Janssen, J, Jaspers-Fayer, F., Jernigan, T.L., Kapilushniy, D., Kardatzki, B., Buitelaar, J.K., Franke, B., and Heuvel, O.A. van den

Abstract

Contains fulltext : 225388.pdf (Publisher’s version ) (Closed access), OBJECTIVE: Attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data. METHODS: Structural T(1)-weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures). RESULTS: No shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood. CONCLUSIONS: The study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.

Published
2020

8. Mapping Cortical and Subcortical Asymmetry in Obsessive-Compulsive Disorder: Findings From the ENIGMA Consortium

Author

Kong, X-Z, Boedhoe, PSW, Abe, Y, Alonso, P, Ameis, SH, Arnold, PD, Assogna, F, Baker, JT, Batistuzzo, MC, Benedetti, F, Beucke, JC, Bollettini, I, Bose, A, Brem, S, Brennan, BP, Buitelaar, J, Calvo, R, Cheng, Y, Cho, KIK, Dallaspezia, S, Denys, D, Ely, BA, Feusner, J, Fitzgerald, KD, Fouche, J-P, Fridgeirsson, EA, Glahn, DC, Gruner, P, Gursel, DA, Hauser, TU, Hirano, Y, Hoexter, MQ, Hu, H, Huyser, C, James, A, Jaspers-Fayer, F, Kathmann, N, Kaufmann, C, Koch, K, Kuno, M, Kvale, G, Kwon, JS, Lazaro, L, Liu, Y, Lochner, C, Marques, P, Marsh, R, Martinez-Zalacain, I, Mataix-Cols, D, Medland, SE, Menchon, JM, Minuzzi, L, Moreira, PS, Morer, A, Morgado, P, Nakagawa, A, Nakamae, T, Nakao, T, Narayanaswamy, JC, Nurmi, EL, O'Neill, J, Pariente, JC, Perriello, C, Piacentini, J, Piras, F, Pittenger, C, Reddy, YCJ, Rus-Oswald, OG, Sakai, Y, Sato, JR, Schmaal, L, Simpson, HB, Soreni, N, Soriano-Mas, C, Spalletta, G, Stern, ER, Stevens, MC, Stewart, SE, Szeszko, PR, Tolin, DF, Tsuchiyagaito, A, van Rooij, D, van Wingen, GA, Venkatasubramanian, G, Wang, Z, Yun, J-Y, Thompson, PM, Stein, DJ, van den Heuvel, OA, Francks, C, Kong, X-Z, Boedhoe, PSW, Abe, Y, Alonso, P, Ameis, SH, Arnold, PD, Assogna, F, Baker, JT, Batistuzzo, MC, Benedetti, F, Beucke, JC, Bollettini, I, Bose, A, Brem, S, Brennan, BP, Buitelaar, J, Calvo, R, Cheng, Y, Cho, KIK, Dallaspezia, S, Denys, D, Ely, BA, Feusner, J, Fitzgerald, KD, Fouche, J-P, Fridgeirsson, EA, Glahn, DC, Gruner, P, Gursel, DA, Hauser, TU, Hirano, Y, Hoexter, MQ, Hu, H, Huyser, C, James, A, Jaspers-Fayer, F, Kathmann, N, Kaufmann, C, Koch, K, Kuno, M, Kvale, G, Kwon, JS, Lazaro, L, Liu, Y, Lochner, C, Marques, P, Marsh, R, Martinez-Zalacain, I, Mataix-Cols, D, Medland, SE, Menchon, JM, Minuzzi, L, Moreira, PS, Morer, A, Morgado, P, Nakagawa, A, Nakamae, T, Nakao, T, Narayanaswamy, JC, Nurmi, EL, O'Neill, J, Pariente, JC, Perriello, C, Piacentini, J, Piras, F, Pittenger, C, Reddy, YCJ, Rus-Oswald, OG, Sakai, Y, Sato, JR, Schmaal, L, Simpson, HB, Soreni, N, Soriano-Mas, C, Spalletta, G, Stern, ER, Stevens, MC, Stewart, SE, Szeszko, PR, Tolin, DF, Tsuchiyagaito, A, van Rooij, D, van Wingen, GA, Venkatasubramanian, G, Wang, Z, Yun, J-Y, Thompson, PM, Stein, DJ, van den Heuvel, OA, and Francks, C

Abstract

BACKGROUND: Lateralized dysfunction has been suggested in obsessive-compulsive disorder (OCD). However, it is currently unclear whether OCD is characterized by abnormal patterns of brain structural asymmetry. Here we carried out what is by far the largest study of brain structural asymmetry in OCD. METHODS: We studied a collection of 16 pediatric datasets (501 patients with OCD and 439 healthy control subjects), as well as 30 adult datasets (1777 patients and 1654 control subjects) from the OCD Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium. Asymmetries of the volumes of subcortical structures, and of measures of regional cortical thickness and surface areas, were assessed based on T1-weighted magnetic resonance imaging scans, using harmonized image analysis and quality control protocols. We investigated possible alterations of brain asymmetry in patients with OCD. We also explored potential associations of asymmetry with specific aspects of the disorder and medication status. RESULTS: In the pediatric datasets, the largest case-control differences were observed for volume asymmetry of the thalamus (more leftward; Cohen's d = 0.19) and the pallidum (less leftward; d = -0.21). Additional analyses suggested putative links between these asymmetry patterns and medication status, OCD severity, or anxiety and depression comorbidities. No significant case-control differences were found in the adult datasets. CONCLUSIONS: The results suggest subtle changes of the average asymmetry of subcortical structures in pediatric OCD, which are not detectable in adults with the disorder. These findings may reflect altered neurodevelopmental processes in OCD.

Published
2020

9. Subcortical Brain Volume, Regional Cortical Thickness, and Cortical Surface Area Across Disorders: Findings From the ENIGMA ADHD, ASD, and OCD Working Groups

Author

Boedhoe, PSW, van Rooij, D, Hoogman, M, Twisk, JWR, Schmaal, L, Abe, Y, Alonso, P, Ameis, SH, Anikin, A, Anticevic, A, Arango, C, Arnold, PD, Asherson, P, Assogna, F, Auzias, G, Banaschewski, T, Baranov, A, Batistuzzo, MC, Baumeister, S, Baur-Streubel, R, Behrmann, M, Bellgrove, MA, Benedetti, F, Beucke, JC, Biederman, J, Bollettini, I, Bose, A, Bralten, J, Bramati, IE, Brandeis, D, Brem, S, Brennan, BP, Busatto, GF, Calderoni, S, Calvo, A, Calvo, R, Castellanos, FX, Cercignani, M, Chaim-Avancini, TM, Chantiluke, KC, Cheng, Y, Cho, KIK, Christakou, A, Coghill, D, Conzelmann, A, Cubillo, A, Dale, AM, Dallaspezia, S, Daly, E, Denys, D, Deruelle, C, Di Martino, A, Dinstein, I, Doyle, AE, Durston, S, Earl, EA, Ecker, C, Ehrlich, S, Ely, BA, Epstein, JN, Ethofer, T, Fair, DA, Fallgatter, AJ, Faraone, S, Fedor, J, Feng, X, Feusner, JD, Fitzgerald, J, Fitzgerald, KD, Fouche, J-P, Freitag, CM, Fridgeirsson, EA, Frodl, T, Gabel, MC, Gallagher, L, Gogberashvili, T, Gori, I, Gruner, P, Gursel, DA, Haar, S, Haavik, J, Hall, GB, Harrison, NA, Hartman, CA, Heslenfeld, DJ, Hirano, Y, Hoekstra, PJ, Hoexter, MQ, Hohmann, S, Hovik, MF, Hu, H, Huyser, C, Jahanshad, N, Jalbrzikowski, M, James, A, Janssen, J, Jaspers-Fayer, F, Jernigan, TL, Kapilushniy, D, Kardatzki, B, Karkashadze, G, Kathmann, N, Kaufmann, C, Kelly, C, Khadka, S, King, JA, Koch, K, Kohls, G, Konrad, K, Kuno, M, Kuntsi, J, Kvale, G, Kwon, JS, Lazaro, L, Lera-Miguel, S, Lesch, K-P, Hoekstra, L, Liu, Y, Lochner, C, Louza, MR, Luna, B, Lundervold, AJ, Malpas, CB, Marques, P, Marsh, R, Martinez-Zalacain, I, Mataix-Cols, D, Mattos, P, McCarthy, H, McGrath, J, Mehta, MA, Menchon, JM, Mennes, M, Martinho, MM, Moreira, PS, Morer, A, Morgado, P, Muratori, F, Murphy, CM, Murphy, DGM, Nakagawa, A, Nakamae, T, Nakao, T, Namazova-Baranova, L, Narayanaswamy, JC, Nicolau, R, Nigg, JT, Novotny, SE, Nurmi, EL, Weiss, EO, Tuura, RLO, O'Hearn, K, O'Neill, J, Oosterlaan, J, Oranje, B, Paloyelis, Y, Parellada, M, Pauli, P, Perriello, C, Piacentini, J, Piras, F, Plessen, KJ, Puig, O, Ramos-Quiroga, JA, Reddy, YCJ, Reif, A, Reneman, L, Retico, A, Rosa, PGP, Rubia, K, Rus, OG, Sakai, Y, Schrantee, A, Schwarz, L, Schweren, LJS, Seitz, J, Shaw, P, Shook, D, Silk, TJ, Simpson, HB, Skokauskas, N, Vila, JCS, Solovieva, A, Soreni, N, Soriano-Mas, C, Spalletta, G, Stern, ER, Stevens, MC, Stewart, SE, Sudre, G, Szeszko, PR, Tamm, L, Taylor, MJ, Tolin, DF, Tosetti, M, Tovar-Moll, F, Tsuchiyagaito, A, van Erp, TGM, van Wingen, GA, Vance, A, Venkatasubramanian, G, Vilarroya, O, Vives-Gilabert, Y, von Polier, GG, Walitza, S, Wallace, GL, Wang, Z, Wolfers, T, Yoncheva, YN, Yun, J-Y, Zanetti, M, Zhou, F, Ziegler, GC, Zierhut, KC, Zwiers, MP, Thompson, PM, Stein, DJ, Buitelaar, J, Franke, B, van den Heuvel, OA, Boedhoe, PSW, van Rooij, D, Hoogman, M, Twisk, JWR, Schmaal, L, Abe, Y, Alonso, P, Ameis, SH, Anikin, A, Anticevic, A, Arango, C, Arnold, PD, Asherson, P, Assogna, F, Auzias, G, Banaschewski, T, Baranov, A, Batistuzzo, MC, Baumeister, S, Baur-Streubel, R, Behrmann, M, Bellgrove, MA, Benedetti, F, Beucke, JC, Biederman, J, Bollettini, I, Bose, A, Bralten, J, Bramati, IE, Brandeis, D, Brem, S, Brennan, BP, Busatto, GF, Calderoni, S, Calvo, A, Calvo, R, Castellanos, FX, Cercignani, M, Chaim-Avancini, TM, Chantiluke, KC, Cheng, Y, Cho, KIK, Christakou, A, Coghill, D, Conzelmann, A, Cubillo, A, Dale, AM, Dallaspezia, S, Daly, E, Denys, D, Deruelle, C, Di Martino, A, Dinstein, I, Doyle, AE, Durston, S, Earl, EA, Ecker, C, Ehrlich, S, Ely, BA, Epstein, JN, Ethofer, T, Fair, DA, Fallgatter, AJ, Faraone, S, Fedor, J, Feng, X, Feusner, JD, Fitzgerald, J, Fitzgerald, KD, Fouche, J-P, Freitag, CM, Fridgeirsson, EA, Frodl, T, Gabel, MC, Gallagher, L, Gogberashvili, T, Gori, I, Gruner, P, Gursel, DA, Haar, S, Haavik, J, Hall, GB, Harrison, NA, Hartman, CA, Heslenfeld, DJ, Hirano, Y, Hoekstra, PJ, Hoexter, MQ, Hohmann, S, Hovik, MF, Hu, H, Huyser, C, Jahanshad, N, Jalbrzikowski, M, James, A, Janssen, J, Jaspers-Fayer, F, Jernigan, TL, Kapilushniy, D, Kardatzki, B, Karkashadze, G, Kathmann, N, Kaufmann, C, Kelly, C, Khadka, S, King, JA, Koch, K, Kohls, G, Konrad, K, Kuno, M, Kuntsi, J, Kvale, G, Kwon, JS, Lazaro, L, Lera-Miguel, S, Lesch, K-P, Hoekstra, L, Liu, Y, Lochner, C, Louza, MR, Luna, B, Lundervold, AJ, Malpas, CB, Marques, P, Marsh, R, Martinez-Zalacain, I, Mataix-Cols, D, Mattos, P, McCarthy, H, McGrath, J, Mehta, MA, Menchon, JM, Mennes, M, Martinho, MM, Moreira, PS, Morer, A, Morgado, P, Muratori, F, Murphy, CM, Murphy, DGM, Nakagawa, A, Nakamae, T, Nakao, T, Namazova-Baranova, L, Narayanaswamy, JC, Nicolau, R, Nigg, JT, Novotny, SE, Nurmi, EL, Weiss, EO, Tuura, RLO, O'Hearn, K, O'Neill, J, Oosterlaan, J, Oranje, B, Paloyelis, Y, Parellada, M, Pauli, P, Perriello, C, Piacentini, J, Piras, F, Plessen, KJ, Puig, O, Ramos-Quiroga, JA, Reddy, YCJ, Reif, A, Reneman, L, Retico, A, Rosa, PGP, Rubia, K, Rus, OG, Sakai, Y, Schrantee, A, Schwarz, L, Schweren, LJS, Seitz, J, Shaw, P, Shook, D, Silk, TJ, Simpson, HB, Skokauskas, N, Vila, JCS, Solovieva, A, Soreni, N, Soriano-Mas, C, Spalletta, G, Stern, ER, Stevens, MC, Stewart, SE, Sudre, G, Szeszko, PR, Tamm, L, Taylor, MJ, Tolin, DF, Tosetti, M, Tovar-Moll, F, Tsuchiyagaito, A, van Erp, TGM, van Wingen, GA, Vance, A, Venkatasubramanian, G, Vilarroya, O, Vives-Gilabert, Y, von Polier, GG, Walitza, S, Wallace, GL, Wang, Z, Wolfers, T, Yoncheva, YN, Yun, J-Y, Zanetti, M, Zhou, F, Ziegler, GC, Zierhut, KC, Zwiers, MP, Thompson, PM, Stein, DJ, Buitelaar, J, Franke, B, and van den Heuvel, OA

Abstract

Objective: Attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data. Methods: Structural T1-weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures). Results: No shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood. Conclusions: The study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.

Published
2020

10. Structural neuroimaging biomarkers for obsessive-compulsive disorder in the ENIGMA-OCD consortium: medication matters

Author

Bruin, WB, Taylor, L, Thomas, RM, Shock, JP, Zhutovsky, P, Abe, Y, Alonso, P, Ameis, SH, Anticevic, A, Arnold, PD, Assogna, F, Benedetti, F, Beucke, JC, Boedhoe, PSW, Bollettini, I, Bose, A, Brem, S, Brennan, BP, Buitelaar, JK, Calvo, R, Cheng, Y, Cho, KIK, Dallaspezia, S, Denys, D, Ely, BA, Feusner, JD, Fitzgerald, KD, Fouche, J-P, Fridgeirsson, EA, Gruner, P, Guersel, DA, Hauser, TU, Hirano, Y, Hoexter, MQ, Hu, H, Huyser, C, Ivanov, I, James, A, Jaspers-Fayer, F, Kathmann, N, Kaufmann, C, Koch, K, Kuno, M, Kvale, G, Kwon, JS, Liu, Y, Lochner, C, Lazaro, L, Marques, P, Marsh, R, Martinez-Zalacain, Mataix-Cols, D, Menchon, JM, Minuzzi, L, Moreira, PS, Morer, A, Morgado, P, Nakagawa, A, Nakamae, T, Nakao, T, Narayanaswamy, JC, Nurmi, EL, O'Neill, J, Pariente, JC, Perriello, C, Piacentini, J, Piras, F, Reddy, YCJ, Rus-Oswald, OG, Sakai, Y, Sato, JR, Schmaal, L, Shimizu, E, Simpson, HB, Soreni, N, Soriano-Mas, C, Spalletta, G, Stern, ER, Stevens, MC, Stewart, SE, Szeszko, PR, Tolin, DF, Venkatasubramanian, G, Wang, Z, Yun, J-Y, van Rooij, D, Thompson, PM, van den Heuvel, OA, Stein, DJ, van Wingen, GA, Bruin, WB, Taylor, L, Thomas, RM, Shock, JP, Zhutovsky, P, Abe, Y, Alonso, P, Ameis, SH, Anticevic, A, Arnold, PD, Assogna, F, Benedetti, F, Beucke, JC, Boedhoe, PSW, Bollettini, I, Bose, A, Brem, S, Brennan, BP, Buitelaar, JK, Calvo, R, Cheng, Y, Cho, KIK, Dallaspezia, S, Denys, D, Ely, BA, Feusner, JD, Fitzgerald, KD, Fouche, J-P, Fridgeirsson, EA, Gruner, P, Guersel, DA, Hauser, TU, Hirano, Y, Hoexter, MQ, Hu, H, Huyser, C, Ivanov, I, James, A, Jaspers-Fayer, F, Kathmann, N, Kaufmann, C, Koch, K, Kuno, M, Kvale, G, Kwon, JS, Liu, Y, Lochner, C, Lazaro, L, Marques, P, Marsh, R, Martinez-Zalacain, Mataix-Cols, D, Menchon, JM, Minuzzi, L, Moreira, PS, Morer, A, Morgado, P, Nakagawa, A, Nakamae, T, Nakao, T, Narayanaswamy, JC, Nurmi, EL, O'Neill, J, Pariente, JC, Perriello, C, Piacentini, J, Piras, F, Reddy, YCJ, Rus-Oswald, OG, Sakai, Y, Sato, JR, Schmaal, L, Shimizu, E, Simpson, HB, Soreni, N, Soriano-Mas, C, Spalletta, G, Stern, ER, Stevens, MC, Stewart, SE, Szeszko, PR, Tolin, DF, Venkatasubramanian, G, Wang, Z, Yun, J-Y, van Rooij, D, Thompson, PM, van den Heuvel, OA, Stein, DJ, and van Wingen, GA

Abstract

No diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Here, we aimed to identify magnetic resonance imaging (MRI) biomarkers for OCD, using 46 data sets with 2304 OCD patients and 2068 healthy controls from the ENIGMA consortium. We performed machine learning analysis of regional measures of cortical thickness, surface area and subcortical volume and tested classification performance using cross-validation. Classification performance for OCD vs. controls using the complete sample with different classifiers and cross-validation strategies was poor. When models were validated on data from other sites, model performance did not exceed chance-level. In contrast, fair classification performance was achieved when patients were grouped according to their medication status. These results indicate that medication use is associated with substantial differences in brain anatomy that are widely distributed, and indicate that clinical heterogeneity contributes to the poor performance of structural MRI as a disease marker.

Published
2020

14. An Empirical Comparison of Meta- and Mega-Analysis With Data From the ENIGMA Obsessive-Compulsive Disorder Working Group

Author

Boedhoe, PSW, Heymans, MW, Schmaal, L, Abe, Y, Alonso, P, Ameis, SH, Anticevic, A, Arnold, PD, Batistuzzo, MC, Benedetti, F, Beucke, JC, Bollettini, I, Bose, A, Brem, S, Calvo, A, Calvo, R, Cheng, Y, Cho, KLK, Ciullo, V, Dallaspezia, S, Denys, D, Feusner, JD, Fitzgerald, KD, Fouches, J-P, Fridgeirsson, EA, Gruner, P, Henna, GL, Hibar, DP, Hoexter, MQ, Hu, H, Huyser, C, Jahanshad, N, James, A, Kathmann, N, Kaufmann, C, Koch, K, Kwon, JS, Lazaro, L, Lochner, C, Marsh, R, Martinez-Zalacain, I, Mataix-Cols, D, Menchon, JM, Minuzzi, L, Morer, A, Nakamae, T, Nakao, T, Narayanaswamy, JC, Nishida, S, Nurmi, EL, O'Neill, J, Piacentini, J, Piras, F, Reddy, YCJ, Reess, TJ, Sakai, Y, Sato, JP, Simpson, HB, Soreni, N, Soriano-Mas, C, Spalletta, G, Stevens, MC, Szeszkos, PP, Tolin, DF, van Wingen, GA, Venkatasubramanian, G, Walitza, S, Wang, Z, Yun, J-Y, Thompson, PM, Stein, DJ, van den Heuvel, OA, Twisk, JWR, Boedhoe, PSW, Heymans, MW, Schmaal, L, Abe, Y, Alonso, P, Ameis, SH, Anticevic, A, Arnold, PD, Batistuzzo, MC, Benedetti, F, Beucke, JC, Bollettini, I, Bose, A, Brem, S, Calvo, A, Calvo, R, Cheng, Y, Cho, KLK, Ciullo, V, Dallaspezia, S, Denys, D, Feusner, JD, Fitzgerald, KD, Fouches, J-P, Fridgeirsson, EA, Gruner, P, Henna, GL, Hibar, DP, Hoexter, MQ, Hu, H, Huyser, C, Jahanshad, N, James, A, Kathmann, N, Kaufmann, C, Koch, K, Kwon, JS, Lazaro, L, Lochner, C, Marsh, R, Martinez-Zalacain, I, Mataix-Cols, D, Menchon, JM, Minuzzi, L, Morer, A, Nakamae, T, Nakao, T, Narayanaswamy, JC, Nishida, S, Nurmi, EL, O'Neill, J, Piacentini, J, Piras, F, Reddy, YCJ, Reess, TJ, Sakai, Y, Sato, JP, Simpson, HB, Soreni, N, Soriano-Mas, C, Spalletta, G, Stevens, MC, Szeszkos, PP, Tolin, DF, van Wingen, GA, Venkatasubramanian, G, Walitza, S, Wang, Z, Yun, J-Y, Thompson, PM, Stein, DJ, van den Heuvel, OA, and Twisk, JWR

Abstract

Objective: Brain imaging communities focusing on different diseases have increasingly started to collaborate and to pool data to perform well-powered meta- and mega-analyses. Some methodologists claim that a one-stage individual-participant data (IPD) mega-analysis can be superior to a two-stage aggregated data meta-analysis, since more detailed computations can be performed in a mega-analysis. Before definitive conclusions regarding the performance of either method can be drawn, it is necessary to critically evaluate the methodology of, and results obtained by, meta- and mega-analyses. Methods: Here, we compare the inverse variance weighted random-effect meta-analysis model with a multiple linear regression mega-analysis model, as well as with a linear mixed-effects random-intercept mega-analysis model, using data from 38 cohorts including 3,665 participants of the ENIGMA-OCD consortium. We assessed the effect sizes and standard errors, and the fit of the models, to evaluate the performance of the different methods. Results: The mega-analytical models showed lower standard errors and narrower confidence intervals than the meta-analysis. Similar standard errors and confidence intervals were found for the linear regression and linear mixed-effects random-intercept models. Moreover, the linear mixed-effects random-intercept models showed better fit indices compared to linear regression mega-analytical models. Conclusions: Our findings indicate that results obtained by meta- and mega-analysis differ, in favor of the latter. In multi-center studies with a moderate amount of variation between cohorts, a linear mixed-effects random-intercept mega-analytical framework appears to be the better approach to investigate structural neuroimaging data.

Published
2019

16. Evidence for the efficacy of bright light therapy for bipolar depression

Author

Benedetti, F., Avery, D. H., Bauer, M., Bunney, W. E., Caliyurt, O., Camardese, Giovanni, Colombo, C., Dallaspezia, S., Henriksen, T. E., Kasper, S., Kuriyama, K., Lam, R. W., Martiny, K., Meesters, Y., Mishima, K., Schulte, R., Suzuki, M., Swie cicki, L., Uchiyama, M., Veale, D., Winkler, D., Wu, J., Kupeli, N. Y., Yoshiike, T., Yu, X., Camardese G. (ORCID:0000-0002-8139-9230), Benedetti, F., Avery, D. H., Bauer, M., Bunney, W. E., Caliyurt, O., Camardese, Giovanni, Colombo, C., Dallaspezia, S., Henriksen, T. E., Kasper, S., Kuriyama, K., Lam, R. W., Martiny, K., Meesters, Y., Mishima, K., Schulte, R., Suzuki, M., Swie cicki, L., Uchiyama, M., Veale, D., Winkler, D., Wu, J., Kupeli, N. Y., Yoshiike, T., Yu, X., and Camardese G. (ORCID:0000-0002-8139-9230)

Abstract

No abstract available

Published
2018

19. Amygdala and the anterior cingulate in the emotional processing in bipolar disorder and schizophrenia. A 3.0 tesla BOLD fMRI study. XXVI Congress of the Collegium Internationale Neuro-Psychopharmacologicum (CINP), Munich 13-17 July

Author

Benedetti F, Radaelli D, Dallaspezia S, Bernasconi A, Giannunzio V, Falini A, Scotti G, Smeraldi E., POLETTI, SARA, COLOMBO , CRISTINA ANNA, CAVALLARO, ROBERTO, Benedetti, F, Poletti, Sara, Radaelli, D, Dallaspezia, S, Bernasconi, A, Giannunzio, V, Colombo, CRISTINA ANNA, Cavallaro, Roberto, Falini, A, Scotti, G, and Smeraldi, E.

Published
2008

23. Spectroscopic changes after chronotherapy of bipolar depression

Author

Bernasconi A, Calabrese G, Benedetti F, Radaelli D, Dallaspezia S, Cadioli M, Falini A, Scotti G, Smeraldi E., COLOMBO , CRISTINA ANNA, Bernasconi, A, Calabrese, G, Benedetti, F, Radaelli, D, Dallaspezia, S, Cadioli, M, Colombo, CRISTINA ANNA, Falini, A, Scotti, G, and Smeraldi, E.

Published
2008

27. Personality disorders and depression: a fMRI study

Author

Radaelli D, Benedetti F, Bernasconi A, Dallaspezia S, Falini A, Scotti G, Smeraldi E., COLOMBO , CRISTINA ANNA, Radaelli, D, Benedetti, F, Bernasconi, A, Dallaspezia, S, Falini, A, Colombo, CRISTINA ANNA, Scotti, G, and Smeraldi, E.

Published
2008

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