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1. Influence of birth cohort on age of onset cluster analysis in bipolar I disorder

Author

Bauer, M., Glenn, T., Alda, M., Andreassen, O.A., Angelopoulos, E., Ardau, R., Baethge, C., Bauer, R., Bellivier, F., Belmaker, R.H., Berk, M., Bjella, T.D., Bossini, L., Bersudsky, Y., Cheung, E.Y.W., Conell, J., Del Zompo, M., Dodd, S., Etain, B., Fagiolini, A., Frye, M.A., Fountoulakis, K.N., Garneau-Fournier, J., Gonzalez-Pinto, A., Harima, H., Hassel, S., Henry, C., Iacovides, A., Isometsä, E.T., Kapczinski, F., Kliwicki, S., König, B., Krogh, R., Kunz, M., Lafer, B., Larsen, E.R., Lewitzka, U., Lopez-Jaramillo, C., MacQueen, G., Manchia, M., Marsh, W., Martinez-Cengotitabengoa, M., Melle, I., Monteith, S., Morken, G., Munoz, R., Nery, F.G., O’Donovan, C., Osher, Y., Pfennig, A., Quiroz, D., Ramesar, R., Rasgon, N., Reif, A., Ritter, P., Rybakowski, J.K., Sagduyu, K., Scippa, A.M., Severus, E., Simhandl, C., Stein, D.J., Strejilevich, S., Hatim Sulaiman, A., Suominen, K., Tagata, H., Tatebayashi, Y., Torrent, C., Vieta, E., Viswanath, B., Wanchoo, M.J., Zetin, M., and Whybrow, P.C.

Published
2015
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2. Solar insolation in springtime influences age of onset of bipolar I disorder

Author

Bauer, M., Glenn, T., Alda, M., Aleksandrovich, M. A., Andreassen, O. A., Angelopoulos, E., Ardau, R., Ayhan, Y., Baethge, C., Bharathram, S. R., Bauer, R., Baune, B. T., Becerra‐Palars, C., Bellivier, F., Belmaker, R. H., Berk, M., Bersudsky, Y., Bicakci, Ş., Birabwa‐Oketcho, H., Bjella, T. D., Bossini, L., Cabrera, J., Cheung, E. Y. W., Del Zompo, M., Dodd, S., Donix, M., Etain, B., Fagiolini, A., Fountoulakis, K. N., Frye, M. A., Gonzalez‐Pinto, A., Gottlieb, J. F., Grof, P., Harima, H., Henry, C., Isometsä, E. T., Janno, S., Kapczinski, F., Kardell, M., Khaldi, S., Kliwicki, S., König, B., Kot, T. L., Krogh, R., Kunz, M., Lafer, B., Landén, M., Larsen, E. R., Lewitzka, U., Licht, R. W., Lopez‐Jaramillo, C., MacQueen, G., Manchia, M., Marsh, W., Martinez‐Cengotitabengoa, M., Melle, I., Meza‐Urzúa, F., Yee Ming, M., Monteith, S., Morken, G., Mosca, E., Munoz, R., Mythri, S. V., Nacef, F., Nadella, R. K., Nery, F. G., Nielsen, R. E., OʼDonovan, C., Omrani, A., Osher, Y., Østermark Sørensen, H., Ouali, U., Pica Ruiz, Y., Pilhatsch, M., Pinna, M., da Ponte, F. D. R., Quiroz, D., Ramesar, R., Rasgon, N., Reddy, M. S., Reif, A., Ritter, P., Rybakowski, J. K., Sagduyu, K., Scippa, Â. M., Severus, E., Simhandl, C., Stein, D. J., Strejilevich, S., Subramaniam, M., Sulaiman, A. H., Suominen, K., Tagata, H., Tatebayashi, Y., Tondo, L., Torrent, C., Vaaler, A. E., Veeh, J., Vieta, E., Viswanath, B., Yoldi‐Negrete, M., Zetin, M., Zgueb, Y., and Whybrow, P. C.

Published
2017
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4. APOE and Alzheimer disease: a major gene with semi-dominant inheritance

Author

Genin, E, Hannequin, D, Wallon, D, Sleegers, K, Hiltunen, M, Combarros, O, Bullido, M J, Engelborghs, S, De Deyn, P, Berr, C, Pasquier, F, Dubois, B, Tognoni, G, Fiévet, N, Brouwers, N, Bettens, K, Arosio, B, Coto, E, Del Zompo, M, Mateo, I, Epelbaum, J, Frank-Garcia, A, Helisalmi, S, Porcellini, E, Pilotto, A, Forti, P, Ferri, R, Scarpini, E, Siciliano, G, Solfrizzi, V, Sorbi, S, Spalletta, G, Valdivieso, F, Vepsäläinen, S, Alvarez, V, Bosco, P, Mancuso, M, Panza, F, Nacmias, B, Bossù, P, Hanon, O, Piccardi, P, Annoni, G, Seripa, D, Galimberti, D, Licastro, F, Soininen, H, Dartigues, J-F, Kamboh, M I, Van Broeckhoven, C, Lambert, J C, Amouyel, P, and Campion, D

Published
2011
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7. Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimerʼs disease

Author

Lambert, J-C, Grenier-Boley, B, Harold, D, Zelenika, D, Chouraki, V, Kamatani, Y, Sleegers, K, Ikram, M A, Hiltunen, M, Reitz, C, Mateo, I, Feulner, T, Bullido, M, Galimberti, D, Concari, L, Alvarez, V, Sims, R, Gerrish, A, Chapman, J, Deniz-Naranjo, C, Solfrizzi, V, Sorbi, S, Arosio, B, Spalletta, G, Siciliano, G, Epelbaum, J, Hannequin, D, Dartigues, J-F, Tzourio, C, Berr, C, Schrijvers, E MC, Rogers, R, Tosto, G, Pasquier, F, Bettens, K, Van Cauwenberghe, C, Fratiglioni, L, Graff, C, Delepine, M, Ferri, R, Reynolds, C A, Lannfelt, L, Ingelsson, M, Prince, J A, Chillotti, C, Pilotto, A, Seripa, D, Boland, A, Mancuso, M, Bossù, P, Annoni, G, Nacmias, B, Bosco, P, Panza, F, Sanchez-Garcia, F, Del Zompo, M, Coto, E, Owen, M, OʼDonovan, M, Valdivieso, F, Caffara, P, Scarpini, E, Combarros, O, Buée, L, Campion, D, Soininen, H, Breteler, M, Riemenschneider, M, Van Broeckhoven, C, Alpérovitch, A, Lathrop, M, Trégouët, D-A, Williams, J, Amouyel, P, consortium, E ADI, and consortium, G ERAD

Published
2013
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11. An examination of the quality and performance of the Alda scale for classifying lithium response phenotypes.

Author

Scott, Jan, Etain, Bruno, Manchia, Mirko, Brichant‐Petitjean, Clara, Geoffroy, Pierre A., Schulze, Thomas, Alda, Martin, Bellivier, Frank, Amare, A, Ardau, R, Backlund, L, Baune, B, Barboza, A, Benabarre, A, Chaumette, B, Chen, H, Chillotti, C, Clark, S, Colom, F, and Del Zompo, M

Subjects
THERAPEUTIC use of lithium, SIGNAL-to-noise ratio, MEASUREMENT errors, PHENOTYPES
Abstract

Objectives: The Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale) is the most widely used clinical measure of lithium response phenotypes. We assess its performance against recommended psychometric and clinimetric standards. Methods: We used data from the Consortium for Lithium Genetics and a French study of lithium response phenotypes (combined sample >2500) to assess reproducibility, responsiveness, validity, and interpretability of the A scale (assessing change in illness activity), the B scale, and its items (assessing confounders of response) and the previously established response categories derived from the Total Score for the Alda scale. Results: The key findings are that the B scale is vulnerable to error measurement. For example, some items contribute little to overall performance of the Alda scale (eg, B2) and that the B scale does not reliably assess a single construct (uncertainty in response). Machine learning models indicate that it may be more useful to employ an algorithm for combining the ratings of individual B items in a sequence that clarifies the noise to signal ratio instead of using a composite score. Conclusions: This study highlights three important topics. First, empirical approaches can help determine which aspects of the performance of any scale can be improved. Second, the B scale of the Alda is best applied as a multidimensional index (identifying several independent confounders of the assessment of response). Third, an integrated science approach to precision psychiatry is vital, otherwise phenotypic misclassifications will undermine the reliability and validity of findings from genetics and biomarker studies. [ABSTRACT FROM AUTHOR]

Published
2020
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12. Impact of sunlight on the age of onset of bipolar disorder

Author

Bauer, M., Glenn, T., Alda, M., Andreassen, O., Ardau, R., Bellivier, F., Berk, M., Bjella, T. D., Bossini, L., Del Zompo, M., Dodd, S., Fagiolini, Andrea, Frye, M. A., Gonzalez Pinto, A., Henry, C., Kapczinski, F., Kliwicki, S., König, B., Kunz, M., Lafer, B., Lopez Jaramillo, C., Manchia, M., Marsh, W., Martinez Cengotitabengoa, M., Melle, I., Morken, G., Munoz, R., Nery, F. G., O'Donovan, C., Pfennig, A., Quiroz, D., Rasgon, N., Reif, A., Rybakowski, J., Sagduyu, K., Simhandl, C., Torrent, C., Vieta, E., Zetin, M., Whybrow, P. C., Farmacologie en Toxicologie, and RS: CARIM School for Cardiovascular Diseases

Subjects
Adult, Aged, 80 and over, Male, bipolar disorder, Adolescent, Photoperiod, Middle Aged, Age of onset, Bipolar disorder, Solar insolation, Sunlight, Article, solar insolation, age of onset, Solar Energy, Humans, Female, Seasons, sunlight, Geography, Medical, Aged, Retrospective Studies
Abstract

Although bipolar disorder has high heritability, the onset occurs during several decades of life, suggesting that social and environmental factors may have considerable influence on disease onset. This study examined the association between the age of onset and sunlight at the location of onset.Data were obtained from 2414 patients with a diagnosis of bipolar I disorder, according to DSM-IV criteria. Data were collected at 24 sites in 13 countries spanning latitudes 6.3 to 63.4 degrees from the equator, including data from both hemispheres. The age of onset and location of onset were obtained retrospectively, from patient records and/or direct interviews. Solar insolation data, or the amount of electromagnetic energy striking the surface of the earth, were obtained from the NASA Surface Meteorology and Solar Energy (SSE) database for each location of onset.The larger the maximum monthly increase in solar insolation at the location of onset, the younger the age of onset (coefficient= -4.724, 95% CI: -8.124 to -1.323, p=0.006), controlling for each country's median age. The maximum monthly increase in solar insolation occurred in springtime. No relationships were found between the age of onset and latitude, yearly total solar insolation, and the maximum monthly decrease in solar insolation. The largest maximum monthly increases in solar insolation occurred in diverse environments, including Norway, arid areas in California, and Chile.The large maximum monthly increase in sunlight in springtime may have an important influence on the onset of bipolar disorder.? 2012 John Wiley and Sons A/S.

Published
2012
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13. Prediction of lithium response using clinical data.

Author

Nunes, A., Ardau, R., Berghöfer, A., Bocchetta, A., Chillotti, C., Deiana, V., Garnham, J., Grof, E., Hajek, T., Manchia, M., Müller‐Oerlinghausen, B., Pinna, M., Pisanu, C., O'Donovan, C., Severino, G., Slaney, C., Suwalska, A., Zvolsky, P., Cervantes, P., and Zompo, M.

Subjects
MACHINE learning, RECEIVER operating characteristic curves, THERAPEUTIC use of lithium, BIOMARKERS
Abstract

Objective: Promptly establishing maintenance therapy could reduce morbidity and mortality in patients with bipolar disorder. Using a machine learning approach, we sought to evaluate whether lithium responsiveness (LR) is predictable using clinical markers. Method: Our data are the largest existing sample of direct interview‐based clinical data from lithium‐treated patients (n = 1266, 34.7% responders), collected across seven sites, internationally. We trained a random forest model to classify LR—as defined by the previously validated Alda scale—against 180 clinical predictors. Results: Under appropriate cross‐validation procedures, LR was predictable in the pooled sample with an area under the receiver operating characteristic curve of 0.80 (95% CI 0.78–0.82) and a Cohen kappa of 0.46 (0.4–0.51). The model demonstrated a particularly low false‐positive rate (specificity 0.91 [0.88–0.92]). Features related to clinical course and the absence of rapid cycling appeared consistently informative. Conclusion: Clinical data can inform out‐of‐sample LR prediction to a potentially clinically relevant degree. Despite the relevance of clinical course and the absence of rapid cycling, there was substantial between‐site heterogeneity with respect to feature importance. Future work must focus on improving classification of true positives, better characterizing between‐ and within‐site heterogeneity, and further testing such models on new external datasets. [ABSTRACT FROM AUTHOR]

Published
2020
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14. Maternal inheritance of manic depression in hemizygotes for the G6PD-Mediterranean mutation. Indirect evidence for Xq28 transmission in Sardinia

Author

Alberto Bocchetta, M.P. Piccardi, G. Quesada, Del Zompo M, and Martinelli

Subjects
Adult, Male, Proband, Heterozygote, congenital, hereditary, and neonatal diseases and abnormalities, Non-Mendelian inheritance, Bipolar Disorder, X Chromosome, Databases, Factual, Mothers, Glucosephosphate Dehydrogenase, medicine.disease_cause, behavioral disciplines and activities, Fathers, Genomic Imprinting, mental disorders, Genetics, medicine, Humans, Allele, Biological Psychiatry, Genetics (clinical), Sex Characteristics, Mutation, Maternal Transmission, business.industry, Homozygote, Xq28, Psychiatry and Mental health, Glucosephosphate Dehydrogenase Deficiency, Italy, Genetic marker, Etiology, Female, business
Abstract

Both X-linkage and a parent-of-origin effect have been hypothesized in manic-depressive disorder. We have previously shown an allelic association between X-linked G6PD deficiency and manic depression in Mediterranean populations. To test both X-linkage and a parent-of-origin effect in manic depression further, we have studied 274 Sardinian manic-depressive probands and their parents. Excess of maternal transmission (P = 0.005) of major affective disorder was found in male probands carrying the G6PD-Mediterranean mutation. Our results provide indirect molecular support for an association between manic depression and the Xq28 chromosome region in Sardinia. Further studies on Xq28 using tests of allelic association and transmission disequilibrium with multiple DNA markers are required, to clarify the nature of the association we have found. Our study cannot implicate or exclude a direct role for G6PD deficiency in the aetiology of manic depression.

Published
1999
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20. Localization of MPP binding sites in the brain of various mammalian species.

Author

Zompo, M., Piccardi, M., Ruiu, S., Albanese, A., and Morelli, M.

Abstract

The distribution and density ofH-MPP binding sites were studied by in vitro quantitative autoradiography in the brain of the mouse, rat and monkey. The highest levels ofH-MPP specific binding were observed in rat brain. The substantia nigra in rat and monkey, and the anterior caudate-putamen formation in mouse and monkey showed the lowest density of autoradiographic grains. The presence of a relatively high density of MPP sites in the hippocampus of all species studied could be of interest to explain some effects of MPTP administration on convulsions caused by chemoconvulsants. The finding of a 60-70% reduction ofH-MPP binding sites in the rat caudate-putamen, on the side of quinolinic acid infusion and no changes after 6-hydroxydopamine lesion of dopaminergic nigrostriatal neurons suggests the presence of these sites mainly on striatal cells. The results suggest that the distribution of MPP binding sites in brain would not seem to be related to MPTP toxicity. [ABSTRACT FROM AUTHOR]

Published
1992
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29. TRT long-term results in lost to follow up patients: Role of the timing and of the reasons of the dropout.

Author

Cipriani, L., Del Zompo, M. R., Lapenna, R., Giommetti, G., Molini, E., and Ricci, G.

Subjects
*PATIENT compliance, *QUESTIONNAIRES, *SURVEYS, *TIME, *TINNITUS treatment, *VISUAL analog scale, *RETROSPECTIVE studies, *CASE-control method, *PATIENT dropouts
Abstract

Aim: To evaluate the TRT results in patients who did not complete the program, with particular reference to the timing and the reasons of their dropout. Design: retrospective case-control study with a telephone survey of 90 patients divided into three groups on the basis of the time of TRT program attendance. A group of control cases (CC) who completed with efficacy the whole TRT program was included.36 patients completed only the first phase of the TRT program (Missing group; M), 34 patients attended additional counseling for less than six months (Non-Compliant; NC), 20 patients attended counseling for more than six months but did not complete the TRT program (Compliant; C). 28 patients (CC) completed with efficacy the whole TRT program. Demographic factors and initial Tinnitus Handicap Inventory (THI) and tinnitus Visual Analogue Scale (VAS) for tinnitus score did not predict patients' dropout from the treatment. Telephonic THI and VAS were significantly lower than the initial ones in all the study groups, except for NC group. To have not shared the TRT program is a fundamental reason for TRT poor results. A single counselling can be effective also in the case the TRT program is not shared, but to follow a part of the TRT program with poor motivations and wrong expectations lead to not satisfactory results. [ABSTRACT FROM AUTHOR]

Published
2017

30. Mania and fluvoxamine.

Author

Burrai, Caterina, Bocchetta, Alberto, Zompo, Maria Del, Burrai, C, Bocchetta, A, and del Zompo, M

Subjects
LETTERS to the editor, ANTIDEPRESSANTS, THERAPEUTIC use of lithium, AMINES, COMBINATION drug therapy, MENTAL depression, DRUG interactions, LITHIUM, BIPOLAR disorder, PHARMACODYNAMICS
Abstract

A letter to the editor is presented that focuses on fluvoxarnine, an antidepressant used in the treatment of mental depression.

Published
1991
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31. Role of dopaminergic system in migraine.

Author

Cherchi A, Stochino E, Piccardi MP, and Del Zompo M

Abstract

The theory that hypersensitivity of dopamine (DA) system is involved in the pathogenesis of migraine has been supported by various authors on the basis of clinical, pharmacological and, recently, genetic evidence. Apomorphine, a selective and specific DA agonist, has a cerebral vasodilatatory effect and increases blood flow significantly in the middle cerebral artery in migraineurs. Processes from central DA neurons terminate in close contact with penetrating arterioles and cerebral capillaries in the cerebral cortex. This finding reaffirms the role of central neurogenic mechanisms in the regulation of the cerebral circulation and, we believe, further supports the major role of dopamine in the neurogenic mechanisms of migraine. Various studies have been carried out to verify the involvement of DA in migraine pathogenesis using molecular genetics as a tool. A positive association between the 'dopaminergic' phenotype of migraine without aura and the D2 receptor gene has been found. To explain dopaminergic hypersensitivity in migraine without aura, we will study the genes encoding proteins involved in the signal transduction system. [ABSTRACT FROM AUTHOR]

Published
2001

39. Association of polygenic score for major depression with response to lithium in patients with bipolar disorder

Author

Amare, Azmeraw T., Schubert, Klaus Oliver, Hou, Liping, Clark, Scott R., Papiol, Sergi, Cearns, Micah, Heilbronner, Urs, Degenhardt, Franziska, Tekola-Ayele, Fasil, Hsu, Yi Hsiang, Shekhtman, Tatyana, Adli, Mazda, Akula, Nirmala, Akiyama, Kazufumi, Ardau, Raffaella, Arias, Bárbara, Aubry, Jean Michel, Backlund, Lena, Bhattacharjee, Abesh Kumar, Bellivier, Frank, Benabarre, Antonio, Bengesser, Susanne, Biernacka, Joanna M., Birner, Armin, Brichant-Petitjean, Clara, Cervantes, Pablo, Chen, Hsi Chung, Chillotti, Caterina, Cichon, Sven, Cruceanu, Cristiana, Czerski, Piotr M., Dalkner, Nina, Dayer, Alexandre, Del Zompo, Maria, DePaulo, J. Raymond, Étain, Bruno, Jamain, Stephane, Falkai, Peter, Forstner, Andreas J., Frisen, Louise, Frye, Mark A., Fullerton, Janice M., Gard, Sébastien, Garnham, Julie S., Goes, Fernando S., Grigoroiu-Serbanescu, Maria, Grof, Paul, Hashimoto, Ryota, Hauser, Joanna, Herms, Stefan, Hoffmann, Per, Hofmann, Andrea, Jiménez, Esther, Kahn, Jean Pierre, Kassem, Layla, Kuo, Po Hsiu, Kato, Tadafumi, Kelsoe, John R., Kittel-Schneider, Sarah, Kliwicki, Sebastian, König, Barbara, Kusumi, Ichiro, Laje, Gonzalo, Landén, Mikael, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan G., Tortorella, Alfonso, Manchia, Mirko, Martinsson, Lina, McCarthy, Michael J., McElroy, Susan L., Colom, Francesc, Mitjans, Marina, Mondimore, Francis M., Monteleone, Palmiero, Nievergelt, Caroline M., Nöthen, Markus M., Novák, Tomas, O’Donovan, Claire, Ozaki, Norio, Ösby, Urban, Pfennig, Andrea, Potash, James B., Reif, Andreas, Wray, Naomi R., Ripke, Stephan, Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M., Abdellaoui, Abdel, Adams, Mark J., Agerbo, Esben, Air, Tracy M., Andlauer, Till F.M., Bacanu, Silviu Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T.F., Bigdeli, Tim B., Binder, Elisabeth B., Blackwood, Douglas H.R., Bryois, Julien, Buttenschøn, Henriette N., Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane varregaard, Clarke, Toni Kim, Coleman, Jonathan R.I., Colodro-Conde, Lucía, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E., Davies, Gail, Deary, Ian J., Derks, Eske M., Direk, Nese, Dolan, Conor V., Dunn, Erin C., Eley, Thalia C., Escott-Price, Valentina, Kiadeh, Farnush Farhadi Hassan, Finucane, Hilary K., Frank, Josef, Gaspar, Héléna A., Gill, Michael, Gordon, Scott D., Grove, Jakob, Hall, Lynsey S., Hansen, Christine Søholm, Hansen, Thomas F., Hickie, Ian B., Homuth, Georg, Horn, Carsten, Hottenga, Jouke Jan, Hougaard, David M., Ising, Marcus, Jansen, Rick, Jorgenson, Eric, Knowles, James A., Kohane, Isaac S., Kraft, Julia, Kretzschmar, Warren W., Krogh, Jesper, Kutalik, Zoltán, Li, Yihan, Lind, Penelope A., MacIntyre, Donald J., MacKinnon, Dean F., Maier, Robert M., Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E., Mehta, Divya, Middeldorp, Christel M., Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Montgomery, Grant W., Mostafavi, Sara, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G., Nyholt, Dale R., O’Reilly, Paul F., Oskarsson, Hogni, Owen, Michael J., Painter, Jodie N., Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Peterson, Roseann E., Pettersson, Erik, Peyrot, Wouter J., Pistis, Giorgio, Posthuma, Danielle, Quiroz, Jorge A., Qvist, Per, Rice, John P., Riley, Brien P., Rivera, Margarita, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C., Shen, Ling, Shi, Jianxin, Shyn, Stanley I., Sigurdsson, Engilbert, Sinnamon, Grant C.B., Smit, Johannes H., Smith, Daniel J., Stefansson, Hreinn, Steinberg, Stacy, Streit, Fabian, Strohmaier, Jana, Tansey, Katherine E., Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A., Thorgeirsson, Thorgeir E., Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, André G., Umbricht, Daniel, Van der Auwera, Sandra, van Hemert, Albert M., Viktorin, Alexander, Visscher, Peter M., Wang, Yunpeng, Webb, Bradley T., Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Witt, Stephanie H., Wu, Yang, Xi, Hualin S., Yang, Jian, Zhang, Futao, Arolt, Volker, Baune, Bernhard T., Berger, Klaus, Boomsma, Dorret I., Dannlowski, Udo, de Geus, E. J.C., Domenici, Enrico, Domschke, Katharina, Esko, Tõnu, Grabe, Hans J., Hamilton, Steven P., Hayward, Caroline, Heath, Andrew C., Kendler, Kenneth S., Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S., Lucae, Susanne, Madden, Pamela A.F., Magnusson, Patrik K., Martin, Nicholas G., McIntosh, Andrew M., Metspalu, Andres, Mors, Ole, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Nordentoft, Merete, O’Donovan, Michael C., Paciga, Sara A., Pedersen, Nancy L., Penninx, Brenda W.J.H., Perlis, Roy H., Porteous, David J., Preisig, Martin, Rietschel, Marcella, Schaefer, Catherine, Schulze, Thomas G., Smoller, Jordan W., Stefansson, Kari, Tiemeier, Henning, Uher, Rudolf, Völzke, Henry, Weissman, Myrna M., Werge, Thomas, Lewis, Cathryn M., Levinson, Douglas F., Breen, Gerome, Børglum, Anders D., Sullivan, Patrick F., Reininghaus, Eva, Rouleau, Guy A., Rybakowski, Janusz K., Schalling, Martin, Schofield, Peter R., Schweizer, Barbara W., Severino, Giovanni, Shilling, Paul D., Shimoda, Katzutaka, Simhandl, Christian, Slaney, Claire M., Squassina, Alessio, Stamm, Thomas, Stopkova, Pavla, Maj, Mario, Turecki, Gustavo, Vieta, Eduard, Veeh, Julia, Wright, Adam, Zandi, Peter P., Mitchell, Philip B., Bauer, Michael, Alda, Martin, McMahon, Francis J., APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D), Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Human genetics, APH - Digital Health, APH - Methodology, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Complex Trait Genetics, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Jamain, Stéphane, University of Adelaide, South Australian Health and Medical Research Institute [ Adelaide] (SAHMRI), Mental Health Services [Adelaide, SA, Australia], National Institute of Mental Health (NIMH), Ludwig Maximilian University [Munich] (LMU), Georg-August-University = Georg-August-Universität Göttingen, Institut für Genetik - Universität Bonn / Institute of Genetics - University of Bonn, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Harvard Medical School [Boston] (HMS), Harvard School of Public Health, University of California [San Diego] (UC San Diego), University of California (UC), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Dokkyo Medical University, Università degli Studi di Cagliari = University of Cagliari (UniCa), Universitat Autònoma de Barcelona (UAB), Centro de Investigación Biomédica en Red de Salud Mental [Barcelona, Spain] (CIBERSAM), Hospital Sant Joan de Déu [Barcelona], Geneva University Hospital (HUG), Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Karl-Franzens-Universität Graz, Mayo Clinic [Rochester], McGill University Health Center [Montreal] (MUHC), National Taiwan University [Taiwan] (NTU), University Hospital Basel [Basel], Poznan University of Medical Sciences [Poland] (PUMS), Johns Hopkins University (JHU), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Fondation FondaMental [Créteil], IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), University of Basel (Unibas), Neuroscience Research Australia [Sydney, NSW, Australia] (NRA), University of New South Wales [Sydney] (UNSW), Psychiatrie de l'enfant et de l'adolescent [CH C. Perrens, Bordeaux], SECOP - centre hospitalier Charles Perrens, Dalhousie University [Halifax], 'Prof. Dr. Alexandru Obregia' Clinical Hospital of Psychiatry [Bucharest, Romania], Mood Disorders Center of Ottawa (MDCO), University of Ottawa [Ottawa], Osaka University [Osaka], Graduate School of Medicine [Osaka], Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Psychiatrie et Psychologie Clinique de Liaison [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Psychothérapique de Nancy (CPN), National Institutes of Health [Bethesda] (NIH), Environmental Molecular Biology Laboratory (RIKEN), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Goethe-University Frankfurt am Main, Landesklinikum Neunkirchen (LK Neunkirchen), Hokkaido University Graduate School of Medicine [Sapporo, Japan], Sahlgrenska Academy at University of Gothenburg [Göteborg], Research Service VA San Diego Healthcare System, Università degli Studi di Perugia = University of Perugia (UNIPG), University of Cincinnati (UC), IMIM-Hospital del Mar, Generalitat de Catalunya, Max Planck Institute of Experimental Medicine [Göttingen] (MPI), Max-Planck-Gesellschaft, University of Salerno (UNISA), University of the Study of Campania Luigi Vanvitelli, National Institute of Mental Health [Klecany, Czech Republic] (NIMH), Nagoya University Graduate School of Medicine [Japon], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Medical University Graz, Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], Sigmund Freud University (SFU), Douglas Mental Health University Institute [Montréal], University of Heidelberg, Medical Faculty, Black Dog Institute [Sydney, Australia], Johns Hopkins Bloomberg School of Public Health [Baltimore], Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Melbourne Medical School [Melbourne], Faculty of Medicine, Dentistry and Health Sciences [Melbourne], University of Melbourne-University of Melbourne, The Florey Institute of Neuroscience and Mental Health [Parkville, VIC, Australie], University of Melbourne, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium: Naomi R Wray, Stephan Ripke, Manuel Mattheisen, Maciej Trzaskowski, Enda M Byrne, Abdel Abdellaoui, Mark J Adams, Esben Agerbo, Tracy M Air, Till F M Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T F Beekman, Tim B Bigdeli, Elisabeth B Binder, Douglas H R Blackwood, Julien Bryois, Henriette N Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Enrique Castelao, Jane Varregaard Christensen, Toni-Kim Clarke, Jonathan R I Coleman, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E Crawford, Gail Davies, Ian J Deary, Franziska Degenhardt, Eske M Derks, Nese Direk, Conor V Dolan, Erin C Dunn, Thalia C Eley, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K Finucane, Andreas J Forstner, Josef Frank, Héléna A Gaspar, Michael Gill, Fernando S Goes, Scott D Gordon, Jakob Grove, Lynsey S Hall, Christine Søholm Hansen, Thomas F Hansen, Stefan Herms, Ian B Hickie, Per Hoffmann, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M Hougaard, Marcus Ising, Rick Jansen, Eric Jorgenson, James A Knowles, Isaac S Kohane, Julia Kraft, Warren W Kretzschmar, Jesper Krogh, Zoltán Kutalik, Yihan Li, Penelope A Lind, Donald J MacIntyre, Dean F MacKinnon, Robert M Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Patrick McGrath, Peter McGuffin, Sarah E Medland, Divya Mehta, Christel M Middeldorp, Evelin Mihailov, Yuri Milaneschi, Lili Milani, Francis M Mondimore, Grant W Montgomery, Sara Mostafavi, Niamh Mullins, Matthias Nauck, Bernard Ng, Michel G Nivard, Dale R Nyholt, Paul F O'Reilly, Hogni Oskarsson, Michael J Owen, Jodie N Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E Peterson, Erik Pettersson, Wouter J Peyrot, Giorgio Pistis, Danielle Posthuma, Jorge A Quiroz, Per Qvist, John P Rice, Brien P Riley, Margarita Rivera, Saira Saeed Mirza, Robert Schoevers, Eva C Schulte, Ling Shen, Jianxin Shi, Stanley I Shyn, Engilbert Sigurdsson, Grant C B Sinnamon, Johannes H Smit, Daniel J Smith, Hreinn Stefansson, Stacy Steinberg, Fabian Streit, Jana Strohmaier, Katherine E Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A Thomson, Thorgeir E Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G Uitterlinden, Daniel Umbricht, Sandra Van der Auwera, Albert M van Hemert, Alexander Viktorin, Peter M Visscher, Yunpeng Wang, Bradley T Webb, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Stephanie H Witt, Yang Wu, Hualin S Xi, Jian Yang, Futao Zhang, Volker Arolt, Bernhard T Baune, Klaus Berger, Dorret I Boomsma, Sven Cichon, Udo Dannlowski, E J C de Geus, J Raymond DePaulo, Enrico Domenici, Katharina Domschke, Tõnu Esko, Hans J Grabe, Steven P Hamilton, Caroline Hayward, Andrew C Heath, Kenneth S Kendler, Stefan Kloiber, Glyn Lewis, Qingqin S Li, Susanne Lucae, Pamela A F Madden, Patrik K Magnusson, Nicholas G Martin, Andrew M McIntosh, Andres Metspalu, Ole Mors, Preben Bo Mortensen, Bertram Müller-Myhsok, Merete Nordentoft, Markus M Nöthen, Michael C O'Donovan, Sara A Paciga, Nancy L Pedersen, Brenda W J H Penninx, Roy H Perlis, David J Porteous, James B Potash, Martin Preisig, Marcella Rietschel, Catherine Schaefer, Thomas G Schulze, Jordan W Smoller, Kari Stefansson, Henning Tiemeier, Rudolf Uher, Henry Völzke, Myrna M Weissman, Thomas Werge, Cathryn M Lewis, Douglas F Levinson, Gerome Breen, Anders D Børglum, Patrick F Sullivan., Epidemiology, Internal Medicine, Child and Adolescent Psychiatry / Psychology, Georg-August-University [Göttingen], University of California, Universita degli Studi di Cagliari [Cagliari], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), University of Graz, Università degli Studi di Perugia (UNIPG), University of Münster, Karl-Franzens-Universität [Graz, Autriche], Amare, A. T., Schubert, K. O., Hou, L., Clark, S. R., Papiol, S., Cearns, M., Heilbronner, U., Degenhardt, F., Tekola-Ayele, F., Hsu, Y. -H., Shekhtman, T., Adli, M., Akula, N., Akiyama, K., Ardau, R., Arias, B., Aubry, J. -M., Backlund, L., Bhattacharjee, A. K., Bellivier, F., Benabarre, A., Bengesser, S., Biernacka, J. M., Birner, A., Brichant-Petitjean, C., Cervantes, P., Chen, H. -C., Chillotti, C., Cichon, S., Cruceanu, C., Czerski, P. M., Dalkner, N., Dayer, A., Del Zompo, M., Depaulo, J. R., Etain, B., Jamain, S., Falkai, P., Forstner, A. J., Frisen, L., Frye, M. A., Fullerton, J. M., Gard, S., Garnham, J. S., Goes, F. S., Grigoroiu-Serbanescu, M., Grof, P., Hashimoto, R., Hauser, J., Herms, S., Hoffmann, P., Hofmann, A., Jimenez, E., Kahn, J. -P., Kassem, L., Kuo, P. -H., Kato, T., Kelsoe, J. R., Kittel-Schneider, S., Kliwicki, S., Konig, B., Kusumi, I., Laje, G., Landen, M., Lavebratt, C., Leboyer, M., Leckband, S. G., Tortorella, A., Manchia, M., Martinsson, L., Mccarthy, M. J., Mcelroy, S. L., Colom, F., Mitjans, M., Mondimore, F. M., Monteleone, P., Nievergelt, C. M., Nothen, M. M., Novak, T., O'Donovan, C., Ozaki, N., Osby, U., Pfennig, A., Potash, J. B., Reif, A., Wray, N. R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E. M., Abdellaoui, A., Adams, M. J., Agerbo, E., Air, T. M., Andlauer, T. F. M., Bacanu, S. -A., Baekvad-Hansen, M., Beekman, A. T. F., Bigdeli, T. B., Binder, E. B., Blackwood, D. H. R., Bryois, J., Buttenschon, H. N., Bybjerg-Grauholm, J., Cai, N., Castelao, E., Christensen, J., Clarke, T. -K., Coleman, J. R. I., Colodro-Conde, L., Couvy-Duchesne, B., Craddock, N., Crawford, G. E., Davies, G., Deary, I. J., Derks, E. M., Direk, N., Dolan, C. V., Dunn, E. C., Eley, T. C., Escott-Price, V., Kiadeh, F. F. H., Finucane, H. K., Frank, J., Gaspar, H. A., Gill, M., Gordon, S. D., Grove, J., Hall, L. S., Hansen, C. S., Hansen, T. F., Hickie, I. B., Homuth, G., Horn, C., Hottenga, J. -J., Hougaard, D. M., Ising, M., Jansen, R., Jorgenson, E., Knowles, J. A., Kohane, I. S., Kraft, J., Kretzschmar, W. W., Krogh, J., Kutalik, Z., Li, Y., Lind, P. A., Macintyre, D. J., Mackinnon, D. F., Maier, R. M., Maier, W., Marchini, J., Mbarek, H., Mcgrath, P., Mcguffin, P., Medland, S. E., Mehta, D., Middeldorp, C. M., Mihailov, E., Milaneschi, Y., Milani, L., Montgomery, G. W., Mostafavi, S., Mullins, N., Nauck, M., Ng, B., Nivard, M. G., Nyholt, D. R., O'Reilly, P. F., Oskarsson, H., Owen, M. J., Painter, J. N., Pedersen, C. B., Pedersen, M. G., Peterson, R. E., Pettersson, E., Peyrot, W. J., Pistis, G., Posthuma, D., Quiroz, J. A., Qvist, P., Rice, J. P., Riley, B. P., Rivera, M., Mirza, S. S., Schoevers, R., Schulte, E. C., Shen, L., Shi, J., Shyn, S. I., Sigurdsson, E., Sinnamon, G. C. B., Smit, J. H., Smith, D. J., Stefansson, H., Steinberg, S., Streit, F., Strohmaier, J., Tansey, K. E., Teismann, H., Teumer, A., Thompson, W., Thomson, P. A., Thorgeirsson, T. E., Traylor, M., Treutlein, J., Trubetskoy, V., Uitterlinden, A. G., Umbricht, D., Van der Auwera, S., van Hemert, A. M., Viktorin, A., Visscher, P. M., Wang, Y., Webb, B. T., Weinsheimer, S. M., Wellmann, J., Willemsen, G., Witt, S. H., Wu, Y., Xi, H. S., Yang, J., Zhang, F., Arolt, V., Baune, B. T., Berger, K., Boomsma, D. I., Dannlowski, U., de Geus, E. J. C., Domenici, E., Domschke, K., Esko, T., Grabe, H. J., Hamilton, S. P., Hayward, C., Heath, A. C., Kendler, K. S., Kloiber, S., Lewis, G., Li, Q. S., Lucae, S., Madden, P. A. F., Magnusson, P. K., Martin, N. G., Mcintosh, A. M., Metspalu, A., Mors, O., Mortensen, P. B., Muller-Myhsok, B., Nordentoft, M., O'Donovan, M. C., Paciga, S. A., Pedersen, N. L., Penninx, B. W. J. H., Perlis, R. H., Porteous, D. J., Preisig, M., Rietschel, M., Schaefer, C., Schulze, T. G., Smoller, J. W., Stefansson, K., Tiemeier, H., Uher, R., Volzke, H., Weissman, M. M., Werge, T., Lewis, C. M., Levinson, D. F., Breen, G., Borglum, A. D., Sullivan, P. F., Reininghaus, E., Rouleau, G. A., Rybakowski, J. K., Schalling, M., Schofield, P. R., Schweizer, B. W., Severino, G., Shilling, P. D., Shimoda, K., Simhandl, C., Slaney, C. M., Squassina, A., Stamm, T., Stopkova, P., Maj, M., Turecki, G., Vieta, E., Veeh, J., Wright, A., Zandi, P. P., Mitchell, P. B., Bauer, M., Alda, M., Mcmahon, F. J., and Adult Psychiatry

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), Lithium (medication), [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Genome-wide association study, Logistic regression, THERAPY, ddc:616.89, 0302 clinical medicine, Medicine, Major depression, PREDICTORS, Depression (differential diagnoses), RISK, Depression, Psychiatry and Mental health, Quartile, Cohort, AUGMENTATION, medicine.drug, POLARITY, medicine.medical_specialty, GENETICS, Bipolar disorder, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Lithium, PROPHYLACTIC LITHIUM, 03 medical and health sciences, Cellular and Molecular Neuroscience, SDG 3 - Good Health and Well-being, Internal medicine, Humans, ddc:610, AGENTS, Molecular Biology, Genetic association, Depressive Disorder, Major, business.industry, medicine.disease, EFFICACY, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, PHARMACOLOGICAL-TREATMENTS, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

© 2020, The Author(s), under exclusive licence to Springer Nature Limited.Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi+Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18–2.01) and European sample: OR = 1.75 (95% CI: 1.30–2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61–4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD.

Published
2021
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40. Age at onset in bipolar disorder: Investigation of the role of TaqIA polymorphism of DRD2 gene in a Sardinian sample

Author

Squassina, A., Manchia, M., Costa, M., Chillotti, C., Ardau, R., Del Zompo, M., and Severino, G.

Subjects
*GENETICS of bipolar disorder, *AGE of onset, *GENETIC polymorphisms, *PHENOTYPES, *GENES, *LOCUS (Genetics)
Abstract

Abstract: Bipolar disorder (BD) is a highly heterogeneous and heritable psychiatric illness. Age at onset has been shown to be a powerful tool for dissecting both the phenotypic and genetic complexity of BD. In this article, we present findings from an association study between the DRD2 TaqIA polymorphism and age at onset, showing that both alleles and genotypes at this locus associate with early onset BD. [Copyright &y& Elsevier]

Published
2011
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41. NRG1 and BDNF genes in schizophrenia: An association study in an Italian case-control sample

Author

Alessio Squassina, Paola Piccardi, Antonio Vita, Maria Del Zompo, Armida Mucci, Alessandro Rossi, Stefano Pini, Silvana Galderisi, Squassina, A, Piccardi, P, DEL ZOMPO, M, Rossi, A, Vita, A, Pini, S, Mucci, Armida, and Galderisi, Silvana

Subjects
Adult, Male, Genotype, Neuregulin-1, Single-nucleotide polymorphism, Biology, Gene Frequency, mental disorders, Genetic variation, Haplotype, medicine, Humans, Genetic Predisposition to Disease, Allele, Neuregulin 1, Gene-gene interaction, Gene, Biological Psychiatry, Genetics, Polymorphism, Genetic, Brain-Derived Neurotrophic Factor, Middle Aged, medicine.disease, Psychiatry and Mental health, Italy, Schizophrenia, Case-Control Studies, biology.protein, Female, Neurotrophin, Genome-Wide Association Study
Abstract

We tested for associations between five single nucleotide polymorphisms (SNPs) located in the area containing the Neuregulin 1 gene (NRG1) and three SNPs within the brain-derived neutrophic factor gene (BDNF) in an Italian sample consisting of 171 schizophrenia subjects and 349 controls. No association was found for any of the polymorphisms tested, either in single locus or in haplotype analysis.

Published
2010
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