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Characterisation of age and polarity at onset in bipolar disorder
- Janos L. Kalman, Loes M. Olde Loohuis, Annabel Vreeker, Andrew McQuillin, Eli A. Stahl, Douglas Ruderfer, Maria Grigoroiu-Serbanescu, Georgia Panagiotaropoulou, Stephan Ripke, Tim B. Bigdeli, Frederike Stein, Tina Meller, Susanne Meinert, Helena Pelin, Fabian Streit, Sergi Papiol, Mark J. Adams, Rolf Adolfsson, Kristina Adorjan, Ingrid Agartz, Sofie R. Aminoff, Heike Anderson-Schmidt, Ole A. Andreassen, Raffaella Ardau, Jean-Michel Aubry, Ceylan Balaban, Nicholas Bass, Bernhard T. Baune, Frank Bellivier, Antoni Benabarre, Susanne Bengesser, Wade H Berrettini, Marco P. Boks, Evelyn J. Bromet, Katharina Brosch, Monika Budde, William Byerley, Pablo Cervantes, Catina Chillotti, Sven Cichon, Scott R. Clark, Ashley L. Comes, Aiden Corvin, William Coryell, Nick Craddock, David W. Craig, Paul E. Croarkin, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Udo Dannlowski, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Srdjan Djurovic, Howard J. Edenberg, Mariam Al Eissa, Torbjørn Elvsåshagen, Bruno Etain, Ayman H. Fanous, Frederike Fellendorf, Alessia Fiorentino, Andreas J. Forstner, Mark A. Frye, Janice M. Fullerton, Katrin Gade, Julie Garnham, Elliot Gershon, Michael Gill, Fernando S. Goes, Katherine Gordon-Smith, Paul Grof, Jose Guzman-Parra, Tim Hahn, Roland Hasler, Maria Heilbronner, Urs Heilbronner, Stephane Jamain, Esther Jimenez, Ian Jones, Lisa Jones, Lina Jonsson, Rene S. Kahn, John R. Kelsoe, James L. Kennedy, Tilo Kircher, George Kirov, Sarah Kittel-Schneider, Farah Klöhn-Saghatolislam, James A. Knowles, Thorsten M. Kranz, Trine Vik Lagerberg, Mikael Landen, William B. Lawson, Marion Leboyer, Qingqin S. Li, Mario Maj, Dolores Malaspina, Mirko Manchia, Fermin Mayoral, Susan L. McElroy, Melvin G. McInnis, Andrew M. McIntosh, Helena Medeiros, Ingrid Melle, Vihra Milanova, Philip B. Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Markus M. Nöthen, Tomas Novak, John I. Nurnberger, Niamh O'Brien, Kevin S. O'Connell, Claire O'Donovan, Michael C. O'Donovan, Nils Opel, Abigail Ortiz, Michael J. Owen, Erik Pålsson, Carlos Pato, Michele T. Pato, Joanna Pawlak, Julia-Katharina Pfarr, Claudia Pisanu, James B. Potash, Mark H Rapaport, Daniela Reich-Erkelenz, Andreas Reif, Eva Reininghaus, Jonathan Repple, Hélène Richard-Lepouriel, Marcella Rietschel, Kai Ringwald, Gloria Roberts, Guy Rouleau, Sabrina Schaupp, William A Scheftner, Simon Schmitt, Peter R. Schofield, K. Oliver Schubert, Eva C. Schulte, Barbara Schweizer, Fanny Senner, Giovanni Severino, Sally Sharp, Claire Slaney, Olav B. Smeland, Janet L. Sobell, Alessio Squassina, Pavla Stopkova, John Strauss, Alfonso Tortorella, Gustavo Turecki, Joanna Twarowska-Hauser, Marin Veldic, Eduard Vieta, John B. Vincent, Wei Xu, Clement C. Zai, Peter P. Zandi, Psychiatric Genomics Consortium (PGC) Bipolar Disorder Working Group, International Consortium on Lithium Genetics (ConLiGen), Colombia-US Cross Disorder Collaboration in Psychiatric Genetics, Arianna Di Florio, Jordan W. Smoller, Joanna M. Biernacka, Francis J. McMahon, Martin Alda, Bertram Müller-Myhsok, Nikolaos Koutsouleris, Peter Falkai, Nelson B. Freimer, Till F.M. Andlauer, Thomas G. Schulze, Roel A. Ophoff
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- Journal:
- The British Journal of Psychiatry / Volume 219 / Issue 6 / December 2021
- Published online by Cambridge University Press:
- 25 August 2021, pp. 659-669
- Print publication:
- December 2021
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Background
Studying 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.
Anorexia nervosa trios: behavioral profiles of individuals with anorexia nervosa and their parents
- M. J. Jacobs, S. Roesch, S. A. Wonderlich, R. Crosby, L. Thornton, D. E. Wilfley, W. H. Berrettini, H. Brandt, S. Crawford, M. M. Fichter, K. A. Halmi, C. Johnson, A. S. Kaplan, M. LaVia, J. E. Mitchell, A. Rotondo, M. Strober, D. B. Woodside, W. H. Kaye, C. M. Bulik
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- Journal:
- Psychological Medicine / Volume 39 / Issue 3 / March 2009
- Published online by Cambridge University Press:
- 26 June 2008, pp. 451-461
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Background
Anorexia nervosa (AN) is associated with behavioral traits that predate the onset of AN and persist after recovery. We identified patterns of behavioral traits in AN trios (proband plus two biological parents).
MethodA total of 433 complete trios were collected in the Price Foundation Genetic Study of AN using standardized instruments for eating disorder (ED) symptoms, anxiety, perfectionism, and temperament. We used latent profile analysis and ANOVA to identify and validate patterns of behavioral traits.
ResultsWe distinguished three classes with medium to large effect sizes by mothers' and probands' drive for thinness, body dissatisfaction, perfectionism, neuroticism, trait anxiety, and harm avoidance. Fathers did not differ significantly across classes. Classes were distinguished by degree of symptomatology rather than qualitative differences. Class 1 (~33%) comprised low symptom probands and mothers with scores in the healthy range. Class 2 (~43%) included probands with marked elevations in drive for thinness, body dissatisfaction, neuroticism, trait anxiety, and harm avoidance and mothers with mild anxious/perfectionistic traits. Class 3 (~24%) included probands and mothers with elevations on ED and anxious/perfectionistic traits. Mother–daughter symptom severity was related in classes 1 and 3 only. Trio profiles did not differ significantly by proband clinical status or subtype.
ConclusionsA key finding is the importance of mother and daughter traits in the identification of temperament and personality patterns in families affected by AN. Mother–daughter pairs with severe ED and anxious/perfectionistic traits may represent a more homogeneous and familial variant of AN that could be of value in genetic studies.
Family history of depression is associated with younger age of onset in patients with recurrent depression
- F. Tozzi, I. Prokopenko, J. D. Perry, J. L. Kennedy, A. D. McCarthy, F. Holsboer, W. Berrettini, L. T. Middleton, H. D. Chilcoat, P. Muglia
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- Journal:
- Psychological Medicine / Volume 38 / Issue 5 / May 2008
- Published online by Cambridge University Press:
- 13 February 2008, pp. 641-649
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Background
Genetic epidemiology data suggest that younger age of onset is associated with family history (FH) of depression. The present study tested whether the presence of FH for depression or anxiety in first-degree relatives determines younger age of onset for depression.
MethodA sample of 1022 cases with recurrent major depressive disorder (MDD) was recruited at the Max Planck Institute and at two affiliated hospitals. Patients were assessed using the Schedules for Clinical Assessment in Neuropsychiatry and questionnaires including demographics, medical history, questions on the use of alcohol and tobacco, personality traits and life events. Survival analysis and the Cox proportional hazard model were used to determine whether FH of depression signals earlier age of onset of depression.
ResultsPatients who reported positive FH had a significantly earlier age of onset than patients who did not report FH of depression (log-rank=48, df=1, p<0.0001). The magnitude of association of FH varies by age of onset, with the largest estimate for MDD onset before age 20 years (hazard ratio=2.2, p=0.0009), whereas FH is not associated with MDD for onset after age 50 years (hazard ratio=0.89, p=0.5). The presence of feelings of guilt, anxiety symptoms and functional impairment due to depressive symptoms appear to characterize individuals with positive FH of depression.
ConclusionsFH of depression contributes to the onset of depression at a younger age and may affect the clinical features of the illness.
CSF Neuropeptides in Euthymic Bipolar Patients and Controls
- Wade H. Berrettini, John I. Nurnberger, Jr., Robert L. Zerbe, Philip W. Gold, George P. Chrousos, Thomas Tomai
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- Journal:
- The British Journal of Psychiatry / Volume 150 / Issue 2 / February 1987
- Published online by Cambridge University Press:
- 02 January 2018, pp. 208-212
- Print publication:
- February 1987
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Levels of vasopressin, somatostatin, neurotensin, vasoactive intestinal peptide, corticotrophin-releasing factor and adrenocorticotrophin in CSF were determined in lithium-treated and unmedicated euthymic bipolar patients and controls, in a search for a trait marker in affective disorder. No group differences in levels of these peptides were found. Highly significant positive correlations were found among these peptides (with the exception of neurotensin), suggesting that their presence in CSF is functionally significant, as opposed to the result of random diffusion from the interstitial space of the brain.