• 1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans 

      Sønderby, Ida Elken; van der Meer, Dennis; Moreau, Clara; Kaufmann, Tobias; Walters, G. Bragi; Ellegaard, Maria; Abdellaoui, Abdel; Ames, David; Amunts, Katrin; Andersson, Micael; Armstrong, Nicola J.; Bernard, Manon; Blackburn, Nicholas B.; Blangero, John; Boomsma, Dorret I.; Brodaty, Henry; Brouwer, Rachel M.; Bülow, Robin; Bøen, Rune; Cahn, Wiepke; Calhoun, Vince D.; Caspers, Svenja; Ching, Christopher R. K.; Cichon, Sven; Ciufolini, Simone; Crespo-Facorro, Benedicto; Curran, Joanne E.; Dale, Anders M.; Dalvie, Shareefa; Dazzan, Paola; de Geus, Eco J. C.; Zubicaray, Greig I. de; Zwarte, Sonja M. C. de; Desrivieres, Sylvane; Doherty, Joanne L.; Donohoe, Gary; Draganski, Bogdan; Ehrlich, Stefan; Eising, Else; Espeseth, Thomas; Fejgin, Kim; Fisher, Simon E.; Fladby, Tormod; Frei, Oleksandr; Frouin, Vincent; Fukunaga, Masaki; Gareau, Thomas; Ge, Tian; Glahn, David C.; Grabe, Hans J.; Groenewold, Nynke A.; Gustafsson, Omar; Haavik, Jan; Haberg, Asta Kristine; Hall, Jeremy; Hashimoto, Ryota; Hehir-Kwa, Jayne Y.; Hibar, Derrek P.; Hillegers, Manon H. J.; Hoffmann, Per; Holleran, Laurena; Holmes, Avram J.; Johansson, Stefan; Jönsson, Erik Gunnar; Hellard, Stephanie Francoise Claire Le; Lundervold, Arvid; Lundervold, Astri J.; Moberget, Torgeir; Nordvik, Jan Egil; Sando, Sigrid Botne; Steen, Vidar Martin; Tamnes, Christian Krog; Agartz, Ingrid; Djurovic, Srdjan; Westlye, Lars Tjelta; Andreassen, Ole; Homuth, Georg; Hottenga, Jouke-Jan; Hulshoff Pol, Hilleke E.; Ikeda, Masashi; Jahanshad, Neda; Jockwitz, Christiane; Jørgensen, Niklas R.; Kikuchi, Masataka; Knowles, Emma E. M.; Kumar, Kuldeep; Leu, Costin; Linden, David E. J.; Liu, Jingyu; Maillard, Anne M.; Martin, Nicholas G.; Martin-Brevet, Sandra; Mather, Karen A.; Mathias, Samuel R.; McMahon, Katie L.; McRae, Allan F.; Medland, Sarah E.; Meyer-Lindenberg, Andreas; Modenato, Claudia; Monereo Sánchez, Jennifer; Morris, Derek W.; Mühleisen, Thomas W.; Murray, Robin M.; Nielsen, Jacob; Nyberg, Lars; Olde Loohuis, Loes M.; Ophoff, Roel A.; Owen, Michael J.; Paus, Tomas; Pausova, Zdenka; Peralta, Juan M.; Pike, G. Bruce; Prieto, Carlos; Quinlan, Erin B.; Reinbold, Céline S.; Reis Marques, Tiago; Rucker, James J. H.; Sachdev, Perminder S.; Schofield, Peter R.; Schork, Andrew J.; Schumann, Gunter; Shin, Jean; Shumskaya, Elena; Silva, Ana I.; Sisodiya, Sanjay M.; Stein, Dan J.; Strike, Lachlan T.; Suzuki, Ikuo K.; Teumer, Alexander; Thalamuthu, Anbupalam; Tordesillas-Gutiérrez, Diana; Uhlmann, Anne; Ulfarsson, Magnus O.; van ‘t Ent, Dennis; van den Bree, Marianne B. M.; Vanderhaeghen, Pierre; Vassos, Evangelos; Wen, Wei; Wittfeld, Katharina; Wright, Margaret J.; Stefansson, Hreinn; Stefansson, Kari; Jacquemont, Sébastien; Thompson, Paul M. (Journal article; Peer reviewed, 2021)
      Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers ...
    • Autozygosity mapping and time-to-spontaneous delivery in Norwegian parent-offspring trios 

      Solé-Navais, Pol; Bacelis, Jonas; Helgeland, Øyvind; Modzelewska, Dominika; Vaudel, Marc; Flatley, Christopher; Andreassen, Ole; Njølstad, Pål Rasmus; Muglia, Louis J.; Johansson, Stefan; Zhang, Ge; Jacobsson, Bo (Journal article; Peer reviewed, 2020)
      Parental genetic relatedness may lead to adverse health and fitness outcomes in the offspring. However, the degree to which it affects human delivery timing is unknown. We use genotype data from ≃25 000 parent-offspring ...
    • Bidirectional genetic overlap between autism spectrum disorder and cognitive traits 

      Hope, Sigrun; Shadrin, Alexey; Lin, Aihua; Bahrami, Shahram; Rødevand, Linn; Frei, Oleksandr; Hübenette, Saira Jameela; Cheng, Weiqiu; Hindley, Guy; Nag, Heidi Elisabeth; Ulstein, Line; Efrim-Budisteanu, Magdalena; O’Connell, Kevin; Dale, Anders; Djurovic, Srdjan; Nærland, Terje; Andreassen, Ole (Journal article; Peer reviewed, 2023)
      Autism spectrum disorder (ASD) is a highly heritable condition with a large variation in cognitive function. Here we investigated the shared genetic architecture between cognitive traits (intelligence (INT) and educational ...
    • Bio-psycho-social factors’ associations with brain age: a large-scale UK Biobank diffusion study of 35,749 participants 

      Korbmacher, Max; Gurholt, Tiril Pedersen; de Lange, Ann Marie; Van der meer, Dennis; Beck, Dani; Eikefjord, Eli Nina; Lundervold, Arvid; Andreassen, Ole; Maximov, Ivan (Journal article; Peer reviewed, 2023)
      Brain age refers to age predicted by brain features. Brain age has previously been associated with various health and disease outcomes and suggested as a potential biomarker of general health. Few previous studies have ...
    • Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders 

      Andlauer, Till F.M.; Guzman-Parra, José; Streit, Fabian; Strohmaier, Jana; González, Maria José; Flores, Susana Gil; Fabeiro, Francisco J. Cabaleiro; Noriega, Francisco del Río; Perez, Fermin Perez; González, Jesus Haro; Diaz, Guillermo Orozco; Diego-Otero, Yolanda de; Moreno-Küstner, Berta; Auburger, Georg; Degenhardt, Franziska; Heilmann-Heimbach, Stefanie; Herms, Stefan; Hoffmann, Per; Frank, Josef; Foo, Jerome C.; Treutlein, Jens; Witt, Stephanie H.; Cichon, Sven; Kogevinas, Manolis; Bøen, Erlend; Dale, Anders M.; Djurovic, Srdjan; Elvsåshagen, Torbjørn; Reinbold, Céline Sonja; Smeland, Olav Bjerkehagen; Agartz, Ingrid; Melle, Ingrid; Ødegaard, Ketil Joachim; Stordal, Eystein; Andreassen, Ole; Rivas, Fabio; Mayoral, Fermín; Müller-Myhsok, Bertram; Forstner, Andreas J.; Nöthen, Markus M.; Rietschel, Marcella; Stahl, Eli A.; Breen, Gerome; McQuillin, Andrew; Ripke, Stephan; Trubetskoy, Vassily; Mattheisen, Manuel; Wang, Yunpeng; Morken, Gunnar; Vaaler, Arne (Journal article; Peer reviewed, 2021)
      Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) ...
    • Body mass index and childhood symptoms of depression, anxiety, and attention-deficit hyperactivity disorder: A within-family Mendelian randomization study 

      Hughes, Amanda M.; Sanderson, Eleanor; Morris, Tim; Ayorech, Ziada; Tesli, Martin Steen; Ask, Helga; Reichborn-Kjennerud, Ted; Andreassen, Ole; Magnus, Per Minor; Helgeland, Øyvind; Johansson, Stefan; Njølstad, Pål Rasmus; Davey Smith, George; Havdahl, Alexandra Karoline Saasen; Howe, Laura D.; Davies, Neil Martin (Journal article; Peer reviewed, 2022)
      Background: Higher BMI in childhood is associated with emotional and behavioural problems, but these associations may not be causal. Results of previous genetic studies imply causal effects but may reflect influence of ...
    • Boosting Schizophrenia Genetics by Utilizing Genetic Overlap With Brain Morphology 

      van der Meer, Dennis; Shadrin, Alexey; O'Connell, Kevin Sean; Bettella, Francesco; Djurovic, Srdjan; Wolfers, Thomas; Alnæs, Dag; Agartz, Ingrid; Smeland, Olav Bjerkehagen; Melle, Ingrid; Sánchez, Jennifer Monereo; Linden, David E.J.; Dale, Anders; Westlye, Lars Tjelta; Andreassen, Ole; Frei, Oleksandr; Kaufmann, Tobias (Journal article; Peer reviewed, 2022)
      Background Schizophrenia is a complex polygenic disorder with subtle, distributed abnormalities in brain morphology. There are indications of shared genetic architecture between schizophrenia and brain measures despite ...
    • Brain‐wide associations between white matter and age highlight the role of fornix microstructure in brain ageing 

      Korbmacher, Max; de Lange, Ann-Marie; van der Meer, Dennis; Beck, Dani; Eikefjord, Eli Nina; Lundervold, Arvid; Andreassen, Ole; Westlye, Lars Tjelta; Maximov, Ivan (Journal article; Peer reviewed, 2023)
      Unveiling the details of white matter (WM) maturation throughout ageing is a fundamental question for understanding the ageing brain. In an extensive comparison of brain age predictions and age-associations of WM features ...
    • Characterising the shared genetic determinants of bipolar disorder, schizophrenia and risk-taking 

      Hindley, Guy Frederick Lanyon; Bahrami, Shahram; Steen, Nils Eiel; O'Connell, Kevin Sean; Frei, Oleksandr; Shadrin, Alexey; Bettella, Francesco; Rødevand, Linn; Fan, Chun-Chieh; Dale, Anders; Djurovic, Srdjan; Smeland, Olav Bjerkehagen; Andreassen, Ole (Journal article; Peer reviewed, 2021)
      Increased risk-taking is a central component of bipolar disorder (BIP) and is implicated in schizophrenia (SCZ). Risky behaviours, including smoking and alcohol use, are overrepresented in both disorders and associated ...
    • Characterization of the genetic architecture of infant and early childhood body mass index 

      Helgeland, Øyvind; Vaudel, Marc; Sole-Navais, Pol; Flatley, Christopher; Juodakis, Julius; Bacelis, Jonas; Koløen, Ingvild; Knudsen, Gun Peggy Strømstad; Johansson, Bente Berg; Magnus, Per Minor; Reichborn-Kjennerud, Ted; Juliusson, Pétur Benedikt; Stoltenberg, Camilla; Holmen, Oddgeir Lingaas; Andreassen, Ole; Jacobsson, Bo; Njølstad, Pål Rasmus; Johansson, Stefan (Journal article; Peer reviewed, 2022)
      Early childhood obesity is a growing global concern; however, the role of common genetic variation on infant and child weight development is unclear. Here, we identify 46 loci associated with early childhood body mass index ...
    • Clinical predictors of non-response to lithium treatment in the Pharmacogenomics of Bipolar Disorder (PGBD) study 

      Lin, Yan; Maihofer, Adam X.; Stapp, Emma; Ritchey, Megan; Alliey-Rodriguez, Ney; Anand, Amit; Balaraman, Yokesh; Berrettini, Wade H; Bertram, Holli; Bhattacharjee, Abesh; Calkin, Cynthia V.; Conroy, Carla; Coryell, William; D´Arcangelo, Nicole; DeModena, Anna; Biernacka, Joanna M.; Fisher, Carrie; Frazier, Nicole; Frye, Mark; Gao, Keming; Garnham, Julie; Gershon, Elliot; Glazer, Kara; Goes, Fernando S; Goto, Toyomi; Karberg, Elizabeth; Harrington, Gloria J.; Jakobsen, Petter; Kamali, Masoud; Kelly, Marisa; Leckband, Susan G.; Lohoff, Falk W.; Stautland, Andrea; McCarthy, Michael J.; McInnis, Melvin G.; Mondimore, Francis; Morken, Gunnar; Nurnberger, John I.; Ødegaard, Ketil Joachim; Syrstad, Vigdis Elin Giæver; Ryan, Kelly; Schinagle, Martha; Schøyen, Helle Kristine; Andreassen, Ole; Shaw, Martha; Shilling, Paul D.; Slaney, Claire; Tarwater, Bruce; Calabrese, Joseph R.; Alda, Martin; Nievergelt, Caroline M.; Zandi, Peter P.; Kelsoe, John R. (Journal article; Peer reviewed, 2021)
      Background Lithium is regarded as a first-line treatment for bipolar disorder (BD), but partial response and non-response commonly occurs. There exists a need to identify lithium non-responders prior to initiating treatment. ...
    • Cohort Profile: COVIDMENT: COVID-19 cohorts on mental health across six nations 

      Unnarsdóttir, Anna Bára; Lovik, Anikó; Fawns-Ritchie, Chloe; Ask, Helga; Kõiv, Kadri; Hagen, Kristen; Didriksen, Maria; Christoffersen, Lea Arregui Nordahl; Garðarsson, Alexander Berg; McIntosh, Andrew; Kähler, Anna K.; Campbell, Archie; Hauksdóttir, Arna; Erikstrup, Christian; Mikkelsen, Dorte Helenius; Altschul, Drew; Thordardottir, Edda Bjork; Frans, Emma Maria; Kvale, Gerd; Tómasson, Gunnar; Kariis, Hanna Maria; Jónsdóttir, Harpa Lind; Rúnarsdóttir, Harpa; Magnúsdóttir, Ingibjörg; Eid, Jarle; Jakobsdóttir, Jóhanna; Nielsen, Kaspar René; Kaspersen, Kathrine Agergård; Milani, Lili; Trogstad, Lill-Iren Schou; Yi, Lu; Bruun, Mie Topholm; Sullivan, Patrick F.; Magnus, Per Minor; Shen, Qing; Nesvåg, Ragnar; Brandlistuen, Ragnhild Eek; Mägi, Reedik; Ostrowski, Sisse Rye; Løkhammer, Solveig; Solem, Stian; Reichborn-Kjennerud, Ted; Hansen, Thomas Folkmann; Werge, Thomas; Aspelund, Thor; Porteous, David J.; Fang, Fang; Lehto, Kelli; Andreassen, Ole; Pedersen, Ole Birger Vesterager; Hellard, Stephanie Francoise Claire Le; Valdimarsdóttir, Unnur Anna (Journal article; Peer reviewed, 2021)
    • Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores 

      de Rojas, Itziar; Moreno-Grau, Sonia; Tesi, Niccolo; Grenier-Boley, Benjamin; Andrade, Victor; Jansen, Iris E.; Rongve, Arvid; Aarsland, Dag; Selbæk, Geir; Saltvedt, Ingvild; Sando, Sigrid Botne; Djurovic, Srdjan; Andreassen, Ole; Pedersen, Nancy L.; Stringa, Najada; Zettergren, Anna; Hernández, Isabel; Montrreal, Laura; Antunez, Carmen; Antonell, Anna; Tankard, Rick; Bis, Joshua C.; Sims, Rebecca; Bellenguez, Celine; Quintela, Inés; González-Pérez, Antonio; Calero, Miguel; Franco-Macias, Emilio; Macias, Juan; Blesa, Rafael; Cervera-Carles, Laura; Menendez-Gonzalez, Manuel; Frank-Garcia, Ana; Royo, José Luis; Moreno, Fermin; Vilas, Raquel Huerto; Baquero, Miquel; Diez-Fairen, Monica; Lage, Carmen; García-Madrona, Sebastian; Garcia-Gonzalez, Pablo; Alarcón-Martín, Emilio; Valero, Sergi; Sotolongo-Grau, Oscar; Ullgren, Abbe; Naj, Adam C.; Lemstra, Afina W.; Benaque, Alba; Perez-Cordon, Alba; Benussi, Alberto; Rabano, Alberto (Journal article; Peer reviewed, 2021)
      Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical ...
    • Composite immune marker scores associated with severe mental disorders and illness course 

      Ormerod, Monica Bettina E. Greenwood; Ueland, Thor; Werner, Maren Caroline Frogner; Hjell, Gabriela; Rødevand, Linn Nilsen; Sæther, Linn Sofie; Lunding, Synve Hoffart; Johansen, Ingrid Torp; Ueland, Torill; Lagerberg, Trine Vik; Melle, Ingrid; Djurovic, Srdjan; Andreassen, Ole; Steen, Nils Eiel (Journal article; Peer reviewed, 2022)
      Background Low-grade inflammation has been implicated in the pathophysiology of severe mental disorders (SMDs) and a link between immune activation and clinical characteristics is suggested. However, few studies have ...
    • Considerations on brain age predictions from repeatedly sampled data across time 

      Korbmacher, Max; Wang, Mengyun; Eikeland, Rune; Buchert, Ralph; Andreassen, Ole; Espeseth, Thomas; Leonardsen, Esten Høyland; Westlye, Lars Tjelta; Maximov, Ivan; Specht, Karsten (Journal article; Peer reviewed, 2023)
      Introduction Brain age, the estimation of a person's age from magnetic resonance imaging (MRI) parameters, has been used as a general indicator of health. The marker requires however further validation for application in ...
    • Cross-trait genome-wide association analysis of C-reactive protein level and psychiatric disorders 

      Hindley, Guy; Drange, Ole Kristian; Lin, Aihua; Kutrolli, Gleda; Shadrin, Alexey; Parker, Nadine; O'Connell, Kevin Sean; Rødevand, Linn; Cheng, Weiqiu; Bahrami, Shahram; Karadag, Naz; Holen, Børge; Jaholkowski, Piotr Pawel; Woldeyohannes, Markos Tesfaye; Djurovic, Srdjan; Dale, Anders M.; Frei, Oleksandr; Ueland, Thor; Smeland, Olav Bjerkehagen; Andreassen, Ole (Journal article; Peer reviewed, 2023)
      C-reactive protein (CRP) tends to be elevated in individuals with psychiatric disorders. Recent findings have suggested a protective effect of the genetic liability to elevated CRP on schizophrenia risk and a causative ...
    • Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality 

      Oddsson, Asmundur; Sulem, Patrick; Sveinbjornsson, Gardar; Arnadottir, Gudny A.; Steinthorsdottir, Valgerdur; Halldorsson, Gisli H.; Atlason, Bjarni A.; Oskarsson, Gudjon R.; Helgason, Hannes; Nielsen, Henriette Svarre; Westergaard, David; Karjalainen, Juha; Katrinardottir, Hildigunnur; Fridriksdottir, Run; Jensson, Brynjar O.; Tragante, Vinicius; Ferkingstad, Egil; Jónsson, Hákon; Gudjonsson, Sigurjon A.; Beyter, Doruk; Moore, Kristjan H.S.; Thordardottir, Helga B.; Kristmundsdottir, Snædis; Stefansson, Olafur A.; Rantapää Dahlqvist, Solbritt; Sonderby, Ida Elken; Didriksen, Maria; Stridh, Pernilla; Haavik, Jan; Tryggvadottir, Laufey; Frei, Oleksandr; Walters, G. Bragi; Kockum, Ingrid; Hjalgrim, Henrik; Olafsdottir, Thorunn A; Selbæk, Geir; Nyegaard, Mette; Erikstrup, Christian; Brodersen, Thorsten; Sævarsdottir, Sædis; Olsson, Tomas; Nielsen, Kaspar Rene; Haraldsson, Àsgeir; Bruun, Mie Topholm; Hansen, Thomas Folkmann; Steingrimsdottir, Thora; Jacobsen, Rikke Louise; Lie, Rolv T.; Djurovic, Srdjan; Alfredsson, Lars; Portilla, A.L.; Brunak, Søren; Havdahl, Alexandra; Andreassen, Ole (Journal article; Peer reviewed, 2023)
      Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. To explore genetic causes of recessive lethality, we searched for sequence variants with ...
    • Differences in white blood cell proportions between schizophrenia cases and controls are influenced by medication and variations in time of day 

      Villar, Jonelle Marie Dickow; Stavrum, Anne-Kristin Støbakk; Nery Spindola, Leticia Maria; Torsvik, Anja; Bjella, Thomas; Steen, Nils Eiel; Djurovic, Srdjan; Andreassen, Ole; Steen, Vidar Martin; Hellard, Stephanie Francoise Claire Le (Journal article; Peer reviewed, 2023)
      Cases with schizophrenia (SCZ) and healthy controls show differences in white blood cell (WBC) counts and blood inflammation markers. Here, we investigate whether time of blood draw and treatment with psychiatric medications ...
    • Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors 

      Mullins, Niamh; Kang, JooEun; Campos, Adrian I.; Coleman, Jonathan R.I.; Edwards, Alexis C.; Galfalvy, Hanga; Levey, Daniel F.; Lori, Adriana; Shabalin, Andrey A; Andreassen, Ole; Melle, Ingrid; Morken, Gunnar; Starnawska, Anna; Su, Mei-Hsin; Watson, Hunna J; Adams, Mark; Awasthi, Swapnil; Gandal, Michael; Hafferty, Jonathan; Hishimoto, Akitoyo; Kim, Minsoo; Okazaki, Satoshi; Otsuka, Ikuo; Ware, Erin B.; Stephan, Ripke; Bergen, Andrew W.; Berrettini, Wade H.; Bohus, Martin; Brandt, Harry; Chang, Xiao; Chen, Wei J; Chen, Hsi-Chung; Crawford, Steven; Crow, Scott; DiBlasi, Emily; Duriez, Philibert; Fichter, Manfred M; Fernández-Aranda, Fernando; Gallinger, Steven; Glatt, Stephen J.; Gorwood, Philip; Guo, Yiran; Hakonarson, Hakon; Halmi, Katherine A; Hwu, Hai-Gwo; Jain, Sonia; Jamain, Stephane; Jimenez-Murcia, Susana; Johnson, Craig; Djurovic, Srdjan (Journal article; Peer reviewed, 2022)
      Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic ...
    • Dissecting the shared genetic basis of migraine and mental disorders using novel statistical tools 

      Bahrami, Shahram; Hindley, Guy Frederick Lanyon; Winsvold, Bendik K S; O'Connell, Kevin S; Frei, Oleksandr; Shadrin, Alexey; Cheng, Weiqiu; Bettella, Francesco; Rødevand, Linn; Ødegaard, Ketil Joachim; Fan, Chun C; Pirinen, Matti J; Hautakangas, Heidi M; Martinsen, Amy; Skogholt, Anne Heidi; Brumpton, Ben Michael; Willer, Cristen J; Tronvik, Erling Andreas; Kristoffersen, Espen Saxhaug; Zwart, John Anker Henrik; Nielsen, Jonas Bille; Hagen, Knut; Nilsen, Kristian Bernhard; Hveem, Kristian; Stovner, Lars Jacob; Fritsche, Lars; Thomas, Laurent; Pedersen, Linda Margareth; Gabrielsen, Maiken Elvestad; Johnsen, Marianne Bakke; Lie, Marie; Holmen, Oddgeir Lingaas; Børte, Sigrid; Stensland, Synne; Zhou, Wei; Dale, Anders; Djurovic, Srdjan; Smeland, Olav Bjerkehagen; Andreassen, Ole (Journal article; Peer reviewed, 2022)
      Migraine is three times more prevalent in people with bipolar disorder or depression. The relationship between schizophrenia and migraine is less certain although glutamatergic and serotonergic neurotransmission are ...