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1. An examination of the quality and performance of the Alda scale for classifying lithium response phenotypes

Author: Scott, J., Etain, B., Manchia, M., Brichant-Petitjean, C., Geoffroy, P. A., Schulze, T., Alda, M., Bellivier, F., Amare, A., Ardau, R., Backlund, L., Baune, B., Barboza, A., Benabarre, A., Chaumette, B., Chen, H., Chillotti, C., Clark, S., Colom, F., Del Zompo, M., Dalkner, N., Dantas, C., Ferentinos, P., Garnham, J., Jamain, S., Jimenez, E., Khan, J. -P., Kuo, P., Lavebratt, C., Maj, M., Millischer, V., Monteleone, P., Pisanu, C., Potash, J., Reif, A., Reininghaus, E., Schalling, M., Schofield, P., Schubert, K., Severino, G., Slaney, C., Smith, D., Squassina, A., Tondo, L., Vieta, E., and Witt, S.
Subjects: Male, psychometrics, Bipolar Disorder, Scale (ratio), Computer science, media_common.quotation_subject, Sample (statistics), Lithium, Machine learning, computer.software_genre, clinimetrics, 03 medical and health sciences, 0302 clinical medicine, Multidimensional index, Humans, genetics, Quality (business), clinical phenotypes, Biological Psychiatry, Reliability (statistics), Retrospective Studies, media_common, Interpretability, business.industry, Confounding, Reproducibility of Results, Alda scale, 030227 psychiatry, Psychiatry and Mental health, Phenotype, lithium response, Lithium Compounds, Female, Artificial intelligence, Construct (philosophy), business, computer, 030217 neurology & neurosurgery
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.
Published: 2019
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2. 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

3. Association between solar insolation and a history of suicide attempts in bipolar I disorder

Author: Bauer, M. Glenn, T. Alda, M. Andreassen, O.A. Angelopoulos, E. Ardau, R. Ayhan, Y. Baethge, C. 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. Cabrera, J. Wo Cheung, E.Y. 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. Ming, M.Y. Monteith, S. Morken, G. Mosca, E. Mozzhegorov, A.A. Munoz, R. Mythri, S.V. Nacef, F. Nadella, R.K. Nery, F.G. Nielsen, R.E. O'Donovan, C. Omrani, A. Osher, Y. Sørensen, H.Ø. Ouali, U. Ruiz, Y.P. 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. Raghuraman, B.S. Scippa, Â.M. Severus, E. Simhandl, C. Stackhouse, P.W., Jr. Stein, D.J. Strejilevich, S. Subramaniam, M. Sulaiman, A.H. Suominen, K. Tagata, H. Tatebayashi, Y. Tondo, L. Torrent, C. Vaaler, A.E. Vares, E. Veeh, J. Vieta, E. Viswanath, B. Yoldi-Negrete, M. Zetin, M. Zgueb, Y. Whybrow, P.C.
Abstract: In many international studies, rates of completed suicide and suicide attempts have a seasonal pattern that peaks in spring or summer. This exploratory study investigated the association between solar insolation and a history of suicide attempt in patients with bipolar I disorder. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area on Earth. Data were collected previously from 5536 patients with bipolar I disorder at 50 collection sites in 32 countries at a wide range of latitudes in both hemispheres. Suicide related data were available for 3365 patients from 310 onset locations in 51 countries. 1047 (31.1%) had a history of suicide attempt. There was a significant inverse association between a history of suicide attempt and the ratio of mean winter solar insolation/mean summer solar insolation. This ratio is smallest near the poles where the winter insolation is very small compared to the summer insolation. This ratio is largest near the equator where there is relatively little variation in the insolation over the year. Other variables in the model that were positively associated with suicide attempt were being female, a history of alcohol or substance abuse, and being in a younger birth cohort. Living in a country with a state-sponsored religion decreased the association. (All estimated coefficients p < 0.01). In summary, living in locations with large changes in solar insolation between winter and summer may be associated with increased suicide attempts in patients with bipolar disorder. Further investigation of the impacts of solar insolation on the course of bipolar disorder is needed. © 2019 Elsevier Ltd
Published: 2019

4. 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. O'Donovan, 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. Whybrow, P.C.
Abstract: Objective: To confirm prior findings that the larger the maximum monthly increase in solar insolation in springtime, the younger the age of onset of bipolar disorder. Method: Data were collected from 5536 patients at 50 sites in 32 countries on six continents. Onset occurred at 456 locations in 57 countries. Variables included solar insolation, birth-cohort, family history, polarity of first episode and country physician density. Results: There was a significant, inverse association between the maximum monthly increase in solar insolation at the onset location, and the age of onset. This effect was reduced in those without a family history of mood disorders and with a first episode of mania rather than depression. The maximum monthly increase occurred in springtime. The youngest birth-cohort had the youngest age of onset. All prior relationships were confirmed using both the entire sample, and only the youngest birth-cohort (all estimated coefficients P < 0.001). Conclusion: A large increase in springtime solar insolation may impact the onset of bipolar disorder, especially with a family history of mood disorders. Recent societal changes that affect light exposure (LED lighting, mobile devices backlit with LEDs) may influence adaptability to a springtime circadian challenge. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Published: 2017

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

Author: Bauer, M. Glenn, T. Alda, M. Andreassen, O. A. and Angelopoulos, E. Ardau, R. Baethge, C. Bauer, R. and Bellivier, F. Belmaker, R. H. Berk, M. Bjella, T. D. and Bossini, L. Bersudsky, Y. Cheung, E. Y. W. Conell, J. and 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. and Isometsa, E. T. Kapczinski, F. Kliwicki, S. Koenig, B. and Krogh, R. Kunz, M. Lafer, B. Larsen, E. R. Lewitzka, U. and Lopez-Jaramillo, C. MacQueen, G. Manchia, M. Marsh, W. and Martinez-Cengotitabengoa, M. Melle, I. Monteith, S. and Morken, G. Munoz, R. Nery, F. G. O'Donovan, C. Osher, Y. and 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. Sulaiman, A. Hatim Suominen, K. Tagata, H. and Tatebayashi, Y. Torrent, C. Vieta, E. Viswanath, B. and Wanchoo, M. J. Zetin, M. Whybrow, P. C.
Abstract: Purpose: Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database. Methods: The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared. Results: There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups. Conclusion: These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research. (C) 2014 Elsevier Masson SAS. All rights reserved.
Published: 2015

7. Ziprasidone vs clozapine in schizophrenia patients refractory to multiple antipsychotic treatments: the MOZART study

Author: Sacchetti, E., Galluzzo, A., Valsecchi, P., Romeo, F., Gorini, B., Warrington, L., Study Group Regini C, M. O. Z. A. R. T., Aguglia, E, Lang, A, Pascolo, E, Antonini, A, D'Amario, A, Croce, F, Matteucci, M, Bilone, F, Bogetto, Filippo, Rocca, Paola, Cirla, M, Rivoira, E, Castrogiovanni, P, Ciappi, F, Attala, T, Perazzi, A, Corradini, P, Piras, A, Boi, R, Carcangiu, E, Del Zompo, M, Ardau, R, Mulas, S, Ducci, G, Cotugno, A, Accorrà, A, Fazzari, G, Garonna, F, Malara, G, Salvatori, F, Maggini, C, Meduri, M, Di Rosa, A, Cardia, R, Parisi, S, Di Rosa, E, Muscettola, G, Casiello, M, Nardini, M, Di Sciascio, G, Sciota, D, Nivoli, G, Nivoli, A, Lorettu, L, Paladin, C, Petralia, A, Fuda, P, Placidi, G, Rossi, M, Raja, M, Amadori, Siracusano, A, Zanasi, M, and Niolu, C.
Subjects: Male, medicine.medical_treatment, Treatment resistance, Piperazines, law.invention, Randomized controlled trial, law, Adult, Analysis of Variance, Antipsychotic Agents, Body Weight, Clozapine, Disease Progression, Dose-Response Relationship, Drug, Double-Blind Method, Drug Therapy, Combination, Female, Glucose, Humans, Italy, Lipids, Middle Aged, Patient Compliance, Psychiatric Status Rating Scales, Quality of Life, Schizophrenia, Schizophrenic Psychology, Thiazoles, Young, Tolerability, Ziprasidone, Psychiatry and Mental health, Drug Therapy, Combination, Psychology, medicine.drug, medicine.medical_specialty, medicine.drug_class, Young Adult, Dose-Response Relationship, Drug, ziprasidone, Atypical antipsychotic, Internal medicine, medicine, Antipsychotic, Settore MED/25 - Psichiatria, Biological Psychiatry, medicine.disease, Endocrinology, Liver function
Abstract: This 18-week, randomized, flexible-dose, double-blind, double-dummy trial evaluated ziprasidone as an alternative to clozapine in treatment-refractory schizophrenia patients. Patients had a DSM-IV diagnosis of schizophrenia, a history of resistance and/or intolerance to at least three acute cycles with different antipsychotics given at therapeutic doses, PANSS scoreor= 80, and CGI-S scoreor= 4. Patients were randomized to ziprasidone (80-160 mg/day, n = 73) or clozapine (250-600 mg/day, n = 74). On the primary ITT-LOCF analysis, baseline-to-endpoint decreases in PANSS total scores were similar in the ziprasidone (- 25.0 +/- 22.0, 95% CI - 30.2 to - 19.8) and clozapine (- 24.5 +/- 22.5, 95% CI - 29.7 to - 19.2) groups. A progressive and significant reduction from baseline in PANSS total score was observed from day 11 in both study arms. There were also significant improvements on PANSS subscales, CGI-S, CG-I, CDSS, and GAF, without between-drug differences. The two treatment groups had similar rates of early discontinuations due to AEs. AEs were mostly of similar mild-moderate severity in the two groups. There were also no detrimental effects on prolactin, renal and liver function, hematology, and cardiovascular parameters. However, ziprasidone but not clozapine showed a significant reduction of SAS and AIMS scores. Moreover, when compared with clozapine, ziprasidone also had a more favorable metabolic profile, with significant endpoint differences in weight, fasting glucose, total cholesterol, LDL cholesterol, and triglycerides. In conclusion, this trial indicates that both ziprasidone and clozapine, having comparable efficacy coupled with satisfactory general safety and tolerability, may be regarded as valuable options for the short-term treatment of difficult-to-treat schizophrenia patients with a history of multiple resistance and/or intolerance to antipsychotics. The more favorable metabolic profile of ziprasidone may represent an added value that could guide clinicians, at least in the presence of patients at high risk for metabolic disorders.
Published: 2009

8. 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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9. Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients

Author: Michael McCarthy, Claire O'Donovan, Urs Heilbronner, Ichiro Kusumi, Eduard Vieta, Liping Hou, Hsi-Chung Chen, Claire Slaney, Maria Grigoroiu-Serbanescu, Kazufumi Akiyama, Michael Bauer, Janusz K. Rybakowski, Frank Bellivier, Marion Leboyer, Katzutaka Shimoda, Palmiero Monteleone, Cristiana Cruceanu, Alessio Squassina, Stephanie H. Witt, Tadafumi Kato, Giovanni Severino, Alfonso Tortorella, J. Raymond DePaulo, Martin Alda, Louise Frisén, Mazda Adl, Martin Schalling, Per Hoffmann, Susan G. Leckband, Jean-Pierre Kahn, Jean-Michel Aubry, Francis J. McMahon, Sven Cichon, Alexandre Dayer, Tatyana Shekhtman, Franziska Degenhardt, James B. Potash, Bruno Etain, Joseph Frank, Antonio Benabarre, Bernhard T. Baune, Gloria Roberts, Ryota Hashimoto, Tomas Novak, Paul D. Shilling, Julia Veeh, Joanna M. Biernacka, Barbara König, Peter Falkai, Philip B. Mitchell, Urban Ösby, Esther Jiménez, Sébastien Gard, Mark A. Frye, Sarah Kittel-Schneider, Layla Kassem, Fasil Tekola-Ayele, Armin Birner, Cynthia Marie-Claire, Raffaella Ardau, Abesh Kumar Bhattacharjee, Stéphane Jamain, Julie Garnham, Guy A. Rouleau, Caterina Chillotti, Piotr M. Czerski, Thomas G. Schulze, Gustavo Turecki, Anbupalam Thalamuthu, Claudia Pisanu, Azmeraw T. Amare, Marina Mitjans, Sergi Papiol, Mario Maj, Bárbara Arias, Janice M. Fullerton, Nina Dalkner, Peter R. Schofield, Susanne Bengesser, Stefan Herms, Klaus Oliver Schubert, Francis M. Mondimore, Eva Z. Reininghaus, Fernando S. Goes, Lena Backlund, Francesc Colom, Catharina Lavebratt, Christian Simhandl, Marcella Rietschel, Micah Cearns, Mikael Landén, Norio Ozaki, Gonzalo Laje, Barbara W. Schweizer, Nirmala Akula, Andrea Pfennig, Yi-Hsiang Hsu, John R. Kelsoe, Lina Martinsson, Markus M. Nöthen, Caroline M. Nievergelt, Pavla Stopkova, Mirko Manchia, Susan L. McElroy, Peter P. Zandi, Scott R. Clark, Joanna Hauser, Andreas J. Forstner, Po-Hsiu Kuo, Andreas Reif, Maria Del Zompo, Paul Grof, Fabian Streit, Ewa Ferensztajn-Rochowiak, Pablo Cervantes, Thomas Stamm, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Complex Trait Genetics, Psychiatry, APH - Digital Health, Schubert, K. O., Thalamuthu, A., Amare, A. T., Frank, J., Streit, F., Adl, 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., Marie-Claire, C., Cearns, M., Cervantes, P., Chen, H. -C., Chillotti, C., Cichon, S., Clark, S. R., Cruceanu, C., Czerski, P. M., Dalkner, N., Dayer, A., Degenhardt, F., Del Zompo, M., Depaulo, J. R., Etain, B., 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., Heilbronner, U., Herms, S., Hoffmann, P., Hou, L., Hsu, Y. -H., Jamain, S., Jimenez, E., Kahn, J. -P., Kassem, L., Kuo, P. -H., Kato, T., Kelsoe, J., Kittel-Schneider, S., Ferensztajn-Rochowiak, E., Konig, B., Kusumi, I., Laje, G., Landen, M., Lavebratt, C., Leboyer, M., Leckband, S. G., Maj, M., Manchia, M., Martinsson, L., Mccarthy, M. J., Mcelroy, S., Colom, F., Mitjans, M., Mondimore, F. M., Monteleone, P., Nievergelt, C. M., Nothen, M. M., Novak, T., O'Donovan, C., Ozaki, N., Osby, U., Papiol, S., Pfennig, A., Pisanu, C., Potash, J. B., Reif, A., Reininghaus, E., Rouleau, G. A., Rybakowski, J. K., Schalling, M., Schofield, P. R., Schweizer, B. W., Severino, G., Shekhtman, T., Shilling, P. D., Shimoda, K., Simhandl, C., Slaney, C. M., Squassina, A., Stamm, T., Stopkova, P., Tekola-Ayele, F., Tortorella, A., Turecki, G., Veeh, J., Vieta, E., Witt, S. H., Roberts, G., Zandi, P. P., Alda, M., Bauer, M., Mcmahon, F. J., Mitchell, P. B., Schulze, T. G., Rietschel, M., and Baune, B. T.
Subjects: Oncology, Multifactorial Inheritance, Treatment response, medicine.medical_specialty, Lithium (medication), Bipolar disorder, Poor responder, Neurosciences. Biological psychiatry. Neuropsychiatry, Lithium, DISEASE, Article, Cellular and Molecular Neuroscience, Risk Factors, Internal medicine, medicine, Humans, Manic-depressive illness, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Depressió psíquica, METAANALYSIS, Biological Psychiatry, Depression (differential diagnoses), MANIA, Depressive Disorder, Depressive Disorder, Major, Trastorn bipolar, Depression, business.industry, Major, medicine.disease, Pathway analysis, Liti, COMPARATIVE EFFICACY, Psychiatry and Mental health, Mental depression, Schizophrenia, Polygenic risk score, Esquizofrènia, Pharmacogenomics, business, RC321-571, medicine.drug
Abstract: Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium’s therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes. We used fixed effect meta-analysis techniques to develop meta-analytic polygenic risk scores (MET-PRS) from combinations of highly correlated psychiatric traits, namely schizophrenia (SCZ), major depression (MD) and bipolar disorder (BD). We compared the effects of cross-disorder MET-PRS and single genetic trait PRS on lithium response. For the PRS analyses, we included clinical data on lithium treatment response and genetic information for n = 2283 BD cases from the International Consortium on Lithium Genetics (ConLi+Gen; www.ConLiGen.org). Higher SCZ and MD PRSs were associated with poorer lithium treatment response whereas BD-PRS had no association with treatment outcome. The combined MET2-PRS comprising of SCZ and MD variants (MET2-PRS) and a model using SCZ and MD-PRS sequentially improved response prediction, compared to single-disorder PRS or to a combined score using all three traits (MET3-PRS). Patients in the highest decile for MET2-PRS loading had 2.5 times higher odds of being classified as poor responders than patients with the lowest decile MET2-PRS scores. An exploratory functional pathway analysis of top MET2-PRS variants was conducted. Findings may inform the development of future testing strategies for personalized lithium prescribing in BD.
Published: 2021
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10. Variations in seasonal solar insolation are associated with a history of suicide attempts in bipolar I disorder

Author: Bauer, Michael, Glenn, Tasha, Achtyes, Eric, Alda, Martin, Agaoglu, Esen, Altınbaş, Kürşat, Andreassen, Ole, Angelopoulos, Elias, Ardau, Raffaella, Vares, Edgar Arrua, Aydin, Memduha, Ayhan, Yavuz, Baethge, Christopher, Bauer, Rita, Baune, Bernhard, Balaban, Ceylan, Becerra-Palars, Claudia, Behere, Aniruddh, Behere, Prakash, Belete, Habte, Belete, Tilahun, Belizario, Gabriel Okawa, Bellivier, Frank, Belmaker, Robert, Benedetti, Francesco, Berk, Michael, Bersudsky, Yuly, Bicakci, Şule, Birabwa-Oketcho, Harriet, Bjella, Thomas, Brady, Conan, Cabrera, Jorge, Cappucciati, Marco, Castro, Angela Marianne Paredes, Chen, Wei-Ling, Cheung, Eric, Chiesa, Silvia, Crowe, Marie, Cuomo, Alessandro, Dallaspezia, Sara, del Zompo, Maria, Desai, Pratikkumar, Dodd, Seetal, Donix, Markus, Etain, Bruno, Fagiolini, Andrea, Fellendorf, Frederike, Ferensztajn-Rochowiak, Ewa, Fiedorowicz, Jess, Fountoulakis, Kostas, Frye, Mark, Geoffroy, Pierre, Gonzalez-Pinto, Ana, Gottlieb, John, Grof, Paul, Haarman, Bartholomeus, Harima, Hirohiko, Hasse-Sousa, Mathias, Henry, Chantal, Høffding, Lone, Houenou, Josselin, Imbesi, Massimiliano, Isometsä, Erkki, Ivkovic, Maja, Janno, Sven, Johnsen, Simon, Kapczinski, Flávio, Karakatsoulis, Gregory, Kardell, Mathias, Kessing, Lars Vedel, Kim, Seong Jae, König, Barbara, Kot, Timur, Koval, Michael, Kunz, Mauricio, Lafer, Beny, Landén, Mikael, Larsen, Erik, Lenger, Melanie, Lewitzka, Ute, Licht, Rasmus, Lopez-Jaramillo, Carlos, Mackenzie, Alan, Madsen, Helle Østergaard, Madsen, Simone Alberte Kongstad A, Mahadevan, Jayant, Mahardika, Agustine, Manchia, Mirko, Marsh, Wendy, Martinez-Cengotitabengoa, Monica, Martiny, Klaus, Mashima, Yuki, Mcloughlin, Declan, Meesters, Ybe, Melle, Ingrid, Meza-Urzúa, Fátima, Ming, Mok Yee, Monteith, Scott, Moorthy, Muthukumaran, Morken, Gunnar, Mosca, Enrica, Mozzhegorov, Anton, Munoz, Rodrigo, Mythri, Starlin, Nacef, Fethi, Nadella, Ravi, Nakanotani, Takako, Nielsen, René Ernst, O'Donovan, Claire, Omrani, Adel, Osher, Yamima, Ouali, Uta, Pantovic-Stefanovic, Maja, Pariwatcharakul, Pornjira, Petite, Joanne, Pfennig, Andrea, Ruiz, Yolanda Pica, Pilhatsch, Maximilian, Pinna, Marco, Pompili, Maurizio, Porter, Richard, Quiroz, Danilo, Rabelo-Da-Ponte, Francisco Diego, Ramesar, Raj, Rasgon, Natalie, Ratta-Apha, Woraphat, Ratzenhofer, Michaela, Redahan, Maria, Reddy, M., Reif, Andreas, Reininghaus, Eva, Richards, Jenny Gringer, Ritter, Philipp, Rybakowski, Janusz, Sathyaputri, Leela, Scippa, Ângela, Simhandl, Christian, Severus, Emanuel, Smith, Daniel, Smith, José, Stackhouse, Paul, Stein, Dan, Stilwell, Kellen, Strejilevich, Sergio, Su, Kuan-Pin, Subramaniam, Mythily, Sulaiman, Ahmad Hatim, Suominen, Kirsi, Tanra, Andi, Tatebayashi, Yoshitaka, Teh, Wen Lin, Tondo, Leonardo, Torrent, Carla, Tuinstra, Daniel, Uchida, Takahito, Vaaler, Arne, Veeh, Julia, Vieta, Eduard, Viswanath, Biju, Yoldi-Negrete, Maria, Yalcinkaya, Oguz Kaan, Young, Allan, Zgueb, Yosra, Whybrow, Peter, Madsen, Simone Alberte Kongstad A., Bauer, M., Glenn, T., Achtyes, E. D., Alda, M., Agaoglu, E., Altinbas, 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, S., 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., Hoffding, L., Houenou, J., Imbesi, M., Isometsa, E. T., Ivkovic, M., Janno, S., Johnsen, S., Kapczinski, F., Karakatsoulis, G. N., Kardell, M., Kessing, L. V., Kim, S. J., Konig, B., Kot, T. L., Koval, M., Kunz, M., Lafer, B., Landen, M., Larsen, E. R., Lenger, M., Lewitzka, U., Licht, R. W., Lopez-Jaramillo, C., Mackenzie, A., Madsen, H. O., 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-Urzua, 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, A. M., Simhandl, C., Severus, E., Smith, D., Smith, J., Stackhouse, P. W., 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., Etain, Bruno, Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), GHU Paris Psychiatrie et Neurosciences, 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), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Fondation FondaMental [Créteil], Clinical Cognitive Neuropsychiatry Research Program (CCNP), Department of Pathology, and Faculty of Health Sciences
Subjects: Neurophysiology and neuropsychology, Psychiatry, Bipolar disorder, QP351-495, Research, Seasonal variation, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Circadian, Neurosciences. Biological psychiatry. Neuropsychiatry, Solar insolation, Suicide, Sunlight, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, RC321-571
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
Published: 2021
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11. Characterisation of age and polarity at onset in bipolar disorder

Author: Kalman, Janos, Olde Loohuis, Loes, Vreeker, Annabel, Mcquillin, Andrew, Stahl, Eli, Ruderfer, Douglas, Grigoroiu-Serbanescu, Maria, Panagiotaropoulou, Georgia, Ripke, Stephan, Bigdeli, Tim, Stein, Frederike, Meller, Tina, Meinert, Susanne, Pelin, Helena, Streit, Fabian, Papiol, Sergi, Adams, Mark, Adolfsson, Rolf, Adorjan, Kristina, Agartz, Ingrid, Aminoff, Sofie, Anderson-Schmidt, Heike, Andreassen, Ole, Ardau, Raffaella, Aubry, Jean-Michel, Balaban, Ceylan, Bass, Nicholas, Baune, Bernhard, Bellivier, Frank, Benabarre, Antoni, Bengesser, Susanne, Berrettini, Wade, Boks, Marco, Bromet, Evelyn, Brosch, Katharina, Budde, Monika, Byerley, William, Cervantes, Pablo, Chillotti, Catina, Cichon, Sven, Clark, Scott, Comes, Ashley, Corvin, Aiden, Coryell, William, Craddock, Nick, Craig, David, Croarkin, Paul, Cruceanu, Cristiana, Czerski, Piotr, Dalkner, Nina, Dannlowski, Udo, Degenhardt, Franziska, del Zompo, Maria, Depaulo, J Raymond, Djurovic, Srdjan, Edenberg, Howard, Eissa, Mariam Al, Elvsåshagen, Torbjørn, Etain, Bruno, Fanous, Ayman, Fellendorf, Frederike, Fiorentino, Alessia, Forstner, Andreas, Frye, Mark, Fullerton, Janice, Gade, Katrin, Garnham, Julie, Gershon, Elliot, Gill, Michael, Goes, Fernando, Gordon-Smith, Katherine, Grof, Paul, Guzman-Parra, Jose, Hahn, Tim, Hasler, Roland, Heilbronner, Maria, Heilbronner, Urs, Jamain, Stephane, Jimenez, Esther, Jones, Ian, Jones, Lisa, Jonsson, Lina, Kahn, Rene, Kelsoe, John, Kennedy, James, Kircher, Tilo, Kirov, George, Kittel-Schneider, Sarah, Klöhn-Saghatolislam, Farah, Knowles, James, Kranz, Thorsten, Lagerberg, Trine Vik, Landen, Mikael, Lawson, William, Leboyer, Marion, Li, Qingqin, Maj, Mario, Malaspina, Dolores, Manchia, Mirko, Mayoral, Fermin, Mcelroy, Susan, Mcinnis, Melvin, McIntosh, Andrew, Medeiros, Helena, Melle, Ingrid, Milanova, Vihra, Mitchell, Philip, Monteleone, Palmiero, Monteleone, Alessio Maria, Nöthen, Markus, Novak, Tomas, Nurnberger, John, O'Brien, Niamh, O'Connell, Kevin, O'Donovan, Claire, O'Donovan, Michael, Opel, Nils, Ortiz, Abigail, Owen, Michael, Pålsson, Erik, Pato, Carlos, Pato, Michele, Pawlak, Joanna, Pfarr, Julia-Katharina, Pisanu, Claudia, Potash, James, Rapaport, Mark, Reich-Erkelenz, Daniela, Reif, Andreas, Reininghaus, Eva, Repple, Jonathan, Richard-Lepouriel, Hélène, Rietschel, Marcella, Ringwald, Kai, Roberts, Gloria, Rouleau, Guy, Schaupp, Sabrina, Scheftner, William, Schmitt, Simon, Schofield, Peter, Schubert, K Oliver, Schulte, Eva, Schweizer, Barbara, Senner, Fanny, Severino, Giovanni, Sharp, Sally, Slaney, Claire, Smeland, Olav, Sobell, Janet, Squassina, Alessio, Stopkova, Pavla, Strauss, John, Tortorella, Alfonso, Turecki, Gustavo, Twarowska-Hauser, Joanna, Veldic, Marin, Vieta, Eduard, Vincent, John, Xu, Wei, Zai, Clement, Zandi, Peter, Di Florio, Arianna, Smoller, Jordan, Biernacka, Joanna, Mcmahon, Francis, Alda, Martin, Müller-Myhsok, Bertram, Koutsouleris, Nikolaos, Falkai, Peter, Freimer, Nelson, Andlauer, Till, Schulze, Thomas, Ophoff, Roel, Depaulo, J. Raymond, Schubert, K. Oliver, Andlauer, Till F.M., Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Etain, Bruno, Child and Adolescent Psychiatry / Psychology, Psychiatry, Kalman, J. L., Loohuis, L. M. O., Vreeker, A., Mcquillin, A., Stahl, E. A., Ruderfer, D., Grigoroiu-Serbanescu, M., Panagiotaropoulou, G., Ripke, S., Bigdeli, T. B., Stein, F., Meller, T., Meinert, S., Pelin, H., Streit, F., Papiol, S., Adams, M. J., Adolfsson, R., Adorjan, K., Agartz, I., Aminoff, S. R., Anderson-Schmidt, H., Andreassen, O. A., Ardau, R., Aubry, J. -M., Balaban, C., Bass, N., Baune, B. T., Bellivier, F., Benabarre, A., Bengesser, S., Berrettini, W. H., Boks, M. P., Bromet, E. J., Brosch, K., Budde, M., Byerley, W., Cervantes, P., Chillotti, C., Cichon, S., Clark, S. R., Comes, A. L., Corvin, A., Coryell, W., Craddock, N., Craig, D. W., Croarkin, P. E., Cruceanu, C., Czerski, P. M., Dalkner, N., Dannlowski, U., Degenhardt, F., Del Zompo, M., Depaulo, J. R., Djurovic, S., Edenberg, H. J., Al Eissa, M., Elvsashagen, T., Etain, B., Fanous, A. H., Fellendorf, F., Fiorentino, A., Forstner, A. J., Frye, M. A., Fullerton, J. M., Gade, K., Garnham, J., Gershon, E., Gill, M., Goes, F. S., Gordon-Smith, K., Grof, P., Guzman-Parra, J., Hahn, T., Hasler, R., Heilbronner, M., Heilbronner, U., Jamain, S., Jimenez, E., Jones, I., Jones, L., Jonsson, L., Kahn, R. S., Kelsoe, J. R., Kennedy, J. L., Kircher, T., Kirov, G., Kittel-Schneider, S., Klohn-Saghatolislam, F., Knowles, J. A., Kranz, T. M., Lagerberg, T. V., Landen, M., Lawson, W. B., Leboyer, M., Li, Q. S., Maj, M., Malaspina, D., Manchia, M., Mayoral, F., Mcelroy, S. L., Mcinnis, M. G., Mcintosh, A. M., Medeiros, H., Melle, I., Milanova, V., Mitchell, P. B., Monteleone, P., Monteleone, A. M., Nothen, M. M., Novak, T., Nurnberger, J. I., O'Brien, N., O'Connell, K. S., O'Donovan, C., O'Donovan, M. C., Opel, N., Ortiz, A., Owen, M. J., Palsson, E., Pato, C., Pato, M. T., Pawlak, J., Pfarr, J. -K., Pisanu, C., Potash, J. B., Rapaport, M. H., Reich-Erkelenz, D., Reif, A., Reininghaus, E., Repple, J., Richard-Lepouriel, H., Rietschel, M., Ringwald, K., Roberts, G., Rouleau, G., Schaupp, S., Scheftner, W. A., Schmitt, S., Schofield, P. R., Schubert, K. O., Schulte, E. C., Schweizer, B., Senner, F., Severino, G., Sharp, S., Slaney, C., Smeland, O. B., Sobell, J. L., Squassina, A., Stopkova, P., Strauss, J., Tortorella, A., Turecki, G., Twarowska-Hauser, J., Veldic, M., Vieta, E., Vincent, J. B., Xu, W., Zai, C. C., Zandi, P. P., Di Florio, A., Smoller, J. W., Biernacka, J. M., Mcmahon, F. J., Alda, M., Muller-Myhsok, B., Koutsouleris, N., Falkai, P., Freimer, N. B., Andlauer, T. F. M., Schulze, T. G., and Ophoff, R. A.
Subjects: Paper, Multifactorial Inheritance, medicine.medical_specialty, Autism Spectrum Disorder, Bipolar disorder, MESH: Age of Onset, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Medizin, GWAS, age at onset, polarity at onset, polygenic score, MESH: Depressive Disorder, Major, BF, Genome-wide association study, Disease, Psykiatri, SDG 3 - Good Health and Well-being, ddc:150, Polarity at onset, Internal medicine, MESH: Bipolar Disorder, Polygenic score, medicine, Humans, Academic Psychiatry, Age of Onset, Genetic association, Psychiatry, MESH: Autism Spectrum Disorder, Depressive Disorder, Major, MESH: Humans, business.industry, Age at onset, Heritability, medicine.disease, Genetic architecture, ddc, Psychiatry and Mental health, Schizophrenia, Autism spectrum disorder, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, MESH: Genome-Wide Association Study, RC0321, MESH: Multifactorial Inheritance, business, Genome-Wide Association Study
Abstract: BackgroundStudying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.AimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.MethodGenome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.ResultsEarlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.ConclusionsAAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Published: 2021
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12. Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report

Author: J. Raymond DePaulo, Martin Alda, Alfonso Tortorella, Susan G. Leckband, Jean-Michel Aubry, James B. Potash, Clara Brichant-Petitjean, Layla Kassem, Joanna Hauser, Tomas Novak, David Zilles, Claire O'Donovan, Rebecca Hoban, Sarah Kittel-Schneider, Claire Slaney, Lena Backlund, Peter Falkai, Andrew T. A. Cheng, John R. Kelsoe, Andrea Pfennig, Janice M. Fullerton, Marcella Rietschel, Caterina Chillotti, Stéphane Jamain, Elise Bui, Po-Hsiu Kuo, Alessio Squassina, Claudio E. M. Banzato, Joanna M. Biernacka, Lisa R. Seymour, Naomi R. Wray, Ichiro Kusumi, Thomas Stamm, Fernando S. Goes, Audrey Nallet, Sarah K. Tighe, Giovanni Severino, Jean-Pierre Kahn, Maria Neuner, Nirmala Akula, Norio Ozaki, Francis J. McMahon, Frank Bellivier, Andreas Reif, Ryota Hashimoto, Barbara W. Schweizer, Palmiero Monteleone, Florian Seemüller, Urs Heilbronner, Sevilla D. Detera-Wadleigh, Pavla Stopkova, Martin Schalling, Julie Garnham, Sébastien Gard, Mark A. Frye, Eva Z. Reininghaus, Lina Martinsson, Urban Ösby, Maria Grigoroiu-Serbanescu, Sara Richardson, Tadafumi Kato, Marion Leboyer, Catharina Lavebratt, Piotr M. Czerski, Scott R. Clark, Daniela Reich-Erkelenz, Sebastian Kliwicki, Guy A. Rouleau, Oliver Gruber, Gonzalo Laje, Adam Wright, Gustavo Turecki, Roy H. Perlis, Takuya Masui, Mirko Manchia, Bernhard T. Baune, Mazda Adli, Michael Bauer, Sven Cichon, Frank Mondimore, Bruno Etain, Philip B. Mitchell, Thomas G. Schulze, Peter P. Zandi, Raffaella Ardau, Peter R. Schofield, Susanne Bengesser, Liping Hou, Janusz K. Rybakowski, Mario Maj, Clarissa de Rosalmeida Dantas, Louise Frisén, O. Schubert, Carlos Jaramillo, Maria Del Zompo, Paul Grof, Cynthia V. Calkin, Jo Steele, Jordan W. Smoller, Alain Malafosse, Manchia, M, Adli, M, Akula, N, Ardau, R, Aubry, Jm, Backlund, L, Banzato, Ce, Baune, Bt, Bellivier, F, Bengesser, S, Biernacka, Jm, Brichant Petitjean, C, Bui, E, Calkin, Cv, Cheng, At, Chillotti, C, Cichon, S, Clark, S, Czerski, Pm, Dantas, C, Zompo, Md, Depaulo, Jr, Detera Wadleigh, Sd, Etain, B, Falkai, P, Frisén, L, Frye, Ma, Fullerton, J, Gard, S, Garnham, J, Goes, F, Grof, P, Gruber, O, Hashimoto, R, Hauser, J, Heilbronner, U, Hoban, R, Hou, L, Jamain, S, Kahn, Jp, Kassem, L, Kato, T, Kelsoe, Jr, Kittel Schneider, S, Kliwicki, S, Kuo, Ph, Kusumi, I, Laje, G, Lavebratt, C, Leboyer, M, Leckband, Sg, López Jaramillo, Ca, Maj, Mario, Malafosse, A, Martinsson, L, Masui, T, Mitchell, Pb, Mondimore, F, Monteleone, P, Nallet, A, Neuner, M, Novák, T, O'Donovan, C, Osby, U, Ozaki, N, Perlis, Rh, Pfennig, A, Potash, Jb, Reich Erkelenz, D, Reif, A, Reininghaus, E, Richardson, S, Rouleau, Ga, Rybakowski, Jk, Schalling, M, Schofield, Pr, Schubert, Ok, Schweizer, B, Seemüller, F, Grigoroiu Serbanescu, M, Severino, G, Seymour, Lr, Slaney, C, Smoller, Jw, Squassina, A, Stamm, T, Steele, J, Stopkova, P, Tighe, Sk, Tortorella, Alfonso Antonio Vincenzo, Turecki, G, Wray, Nr, Wright, A, Zandi, Pp, Zilles, D, Bauer, M, Rietschel, M, Mcmahon, Fj, Schulze, Tg, Alda, M., Department of Psychiatry, Dalhousie University [Halifax], Department of Psychiatry and Psychotherapy, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Unit of Clinical Pharmacology, University-Hospital of Cagliari, Department of Mental Health and Psychiatry, University Hospital of Geneva, Trinity College Dublin-St. James's Hospital, University of Campinas [Campinas] (UNICAMP), University of Adelaide, Pôle de Psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Medical University Graz, Mayo Clinic, Division of Epidemiology and Genetics, Academia Sinica-Institute of Biomedical Sciences (ICB/USP), Universidade de São Paulo (USP)-Universidade de São Paulo (USP), Department of Genomics, Life and Brain Center, University of Bonn, Psychiatric Genetic Unit, Poznan University of Medical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, University of Homburg, Genetics of Mental Illness and Brain Function, Neuroscience Research Australia, Service de psychiatrie adulte, Université Bordeaux Segalen - Bordeaux 2-Hôpital Charles Perrens-Centre Expert Trouble Bipolaire, Mood Disorders Center of Ottawa (MDCO), University of Ottawa [Ottawa], University of Toronto, Georg-August-University [Göttingen], Osaka University Graduate School of Medicine, University of California [San Diego] (UC San Diego), University of California-University of California, Service de Psychiatrie et Psychologie Clinique, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Hôpital Jeanne-d'Arc, Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Center for Brain Science [Wako] (RIKEN CBS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN)-RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Mental Health Sciences Unit, University College of London [London] (UCL), Department of Adult Psychiatry, Institute of Epidemiology and Preventive Medicine, National Taiwan University [Taiwan] (NTU), Hokkaido University Graduate School of Medicine, Molecular Medicine and Surgery department, Karolinska Institutet [Stockholm], Center for Molecular Medicine, Karolinska University Hospital [Stockholm], Department of Pharmacy, Veterans Affairs San Diego Healthcare System, Skaggs School of Pharmacy and Pharmaceutical Sciences [San Diego], University of Antioquia, University of Napoli, School of Psychiatry, University of New South Wales [Sydney] (UNSW)-Black Dog Institute, Prague Psychiatric Center, University of Prague, Fujita Health University School of Medicine, Nagoya University Graduate School of Medicine, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Technische Universität Dresden = Dresden University of Technology (TU Dresden), University of Iowa [Iowa City], Center of Excellence in Neuroscience, CHU de Montréal, Department of Medicine, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM)-Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Psychiatric Hospital, McGill Group for Suicide Studies, Douglas Mental Health University Institute, Queensland Brain Institute, University of Queensland [Brisbane], Department of Mental Health, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU)-Johns Hopkins University (JHU), Department of Genetic Epidemiology in Psychiatry [Mannhein], Universität Heidelberg [Heidelberg]-Central Institute of Mental Health Mannheim, The work on assessment of lithium response has been supported by a grant from Canadian Institutes of Health Research #64410 to MA. MG-S was supported by Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii (UEFISCDI), Bucharest, Romania (grant no. 89/2012). JMA and AN were supported by a grant from the Swiss National Foundation (#32003B_125469/1 to JM Aubry). ConLiGen is in part supported by funds from the Intramural Research Program of the National Institute of Mental Health (NIMH) at the National Institutes of Health (NIH), Department of Health and Human Services, United States Government, Aubry, Jean-Michel, Universidade Estadual de Campinas = University of Campinas (UNICAMP), Universidade de São Paulo = University of São Paulo (USP)-Universidade de São Paulo = University of São Paulo (USP), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Georg-August-University = Georg-August-Universität Göttingen, University of California (UC)-University of California (UC), Guellaen, Georges, Université Bordeaux Segalen - Bordeaux 2-Centre hospitalier Charles Perrens [Bordeaux]-Centre Expert Trouble Bipolaire, and Ikeda, Kazutaka
Subjects: Male, Bipolar Disorder, Lithium (medication), Psychometrics, Psychopharmacology, Epidemiology, International Cooperation, lcsh:Medicine, Lithium, Maintenance Treatment, ConLiGen, ddc:616.89, 0302 clinical medicine, Antimanic Agents, Psychology, lcsh:Science, Reliability (statistics), Psychiatry, Genetics, 0303 health sciences, Multidisciplinary, ASSOCIATION, Genomics, Pharmacoepidemiology, 3. Good health, Mental Health, Phenotype, Treatment Outcome, MAPPING SUSCEPTIBILITY GENES, Behavioral Pharmacology, RELIABILITY, Lithium Compounds, Medicine, Female, Research Article, medicine.drug, Drugs and Devices, MAPPING SUSCEPTIBILITY GENES, PROPHYLACTIC LITHIUM, OBSERVER AGREEMENT, MOOD DISORDERS, ONSET, ASSOCIATION, RELIABILITY, MORTALITY, ILLNESS, AGE, ILLNESS, PROPHYLACTIC LITHIUM, 03 medical and health sciences, AGE, Neuropharmacology, Genomic Medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genome-Wide Association Studies, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Bipolar disorder, ddc:610, Biology, 030304 developmental biology, Mood Disorders, business.industry, MORTALITY, lcsh:R, Computational Biology, Reproducibility of Results, Models, Theoretical, medicine.disease, OBSERVER AGREEMENT, Mood disorders, Pharmacogenetics, Therapies, ONSET, lcsh:Q, Pharmacogenomics, business, 030217 neurology & neurosurgery, Kappa
Abstract: Objective: The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the "Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" scale currently used in the Consortium on Lithium Genetics (ConLiGen) study. Materials and Methods: Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (\(\kappa\))] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling. Results: Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (\(\kappa\) = 0.66 and \(\kappa\) = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (\(ICC_1 = 0.71\) and \(ICC_2 = 0.75\), respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders). Conclusions: We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study.
Published: 2013
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12 results on '"Ardau, R"'

1. An examination of the quality and performance of the Alda scale for classifying lithium response phenotypes

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

3. Association between solar insolation and a history of suicide attempts in bipolar I disorder

4. Solar insolation in springtime influences age of onset of bipolar I disorder

5. Impact of sunlight on the age of onset of bipolar disorder

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

7. Ziprasidone vs clozapine in schizophrenia patients refractory to multiple antipsychotic treatments: the MOZART study

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

9. Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients

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

11. Characterisation of age and polarity at onset in bipolar disorder

12. Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report

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12 results on '"Ardau, R"'

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