Ingrid Melle

• Aas, Monica; Ueland, Torill; Inova, Amina; Melle, Ingrid; Andreassen, Ole Andreas & Steen, Nils Eiel (2020). Childhood Trauma Is Nominally Associated With Elevated Cortisol Metabolism in Severe Mental Disorder. Frontiers in Psychiatry.  ISSN 1664-0640. . doi: 10.3389/fpsyt.2020.00391 Full text in Research Archive.
• Coleman, Jonathan R.I.; Gaspar, Helena A; Bryois, Julien; Byrne, Enda M; Forstner, Andreas J; Holmans, Peter A; de Leeuw, Christiaan A.; Mattheisen, Manuel; McQuillin, Andrew; Whitehead Pavlides, Jennifer M; Pers, Tune H; Ripke, Stephan; Stahl, Eli A.; Steinberg, Stacy; Trubetskoy, Vassily; Trzaskowski, Maciej; Wang, Yunpeng; Abbott, Liam; Abdellaoui, Abdel; Adams, Mark J; Nordin Adolfsson, Annelie; Agerbo, Esben; Akil, Huda; Albani, Diego; Alliey-Rodriguez, Ney; Als, Thomas D.; Andlauer, Till F.M.; Anjorin, Adebayo; Anttila, Verneri; Van Der Auwera, Sandra; Awasthi, Swapnil; Bacanu, Silviu-Alin; Badner, Judith A.; Bækvad-Hansen, Marie; Barchas, Jack D.; Bass, Nicholas; Bauer, Michael; Beekman, Aartjan T.F.; Belliveau, Richard; Bøen, Erlend; Djurovic, Srdjan; Elvsåshagen, Torbjørn; Smeland, Olav Bjerkehagen; Agartz, Ingrid; Melle, Ingrid; Morken, Gunnar; Ødegaard, Ketil Joachim; Stordal, Eystein; Vaaler, Arne; Andreassen, Ole Andreas & Breen, Gerome (2020). The Genetics of the Mood Disorder Spectrum: Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls. Biological Psychiatry.  ISSN 0006-3223. . doi: 10.1016/j.biopsych.2019.10.015 Show summary

  Background: Mood disorders (including major depressive disorder and bipolar disorder) affect 10% to 20% of the population. They range from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Multiple approaches have shown considerable sharing of risk factors across mood disorders despite their diagnostic distinction. Methods: To clarify the shared molecular genetic basis of major depressive disorder and bipolar disorder and to highlight disorder-specific associations, we meta-analyzed data from the latest Psychiatric Genomics Consortium genome-wide association studies of major depression (including data from 23andMe) and bipolar disorder, and an additional major depressive disorder cohort from UK Biobank (total: 185,285 cases, 439,741 controls; nonoverlapping N = 609,424). Results: Seventy-three loci reached genome-wide significance in the meta-analysis, including 15 that are novel for mood disorders. More loci from the Psychiatric Genomics Consortium analysis of major depression than from that for bipolar disorder reached genome-wide significance. Genetic correlations revealed that type 2 bipolar disorder correlates strongly with recurrent and single-episode major depressive disorder. Systems biology analyses highlight both similarities and differences between the mood disorders, particularly in the mouse brain cell types implicated by the expression patterns of associated genes. The mood disorders also differ in their genetic correlation with educational attainment-the relationship is positive in bipolar disorder but negative in major depressive disorder. Conclusions: The mood disorders share several genetic associations, and genetic studies of major depressive disorder and bipolar disorder can be combined effectively to enable the discovery of variants not identified by studying either disorder alone. However, we demonstrate several differences between these disorders. Analyzing subtypes of major depressive disorder and bipolar disorder provides evidence for a genetic mood disorders spectrum.

• Elvsåshagen, Torbjørn; Bahrami, Shahram; van der Meer, Dennis; Agartz, Ingrid; Alnæs, Dag; Barch, Deanna M.; Baur-Streubel, Ramona; Bertolino, Alessandro; Beyer, Mona K.; Blasi, Giuseppe; Borgwardt, Stefan; Boye, Birgitte; Buitelaar, Jan; Bøen, Erlend; Celius, Elisabeth Gulowsen; Cervenka, Simon; Conzelmann, Annette; Coynel, David; di Carlo, Pasquale; Djurovic, Srdjan; Eisenacher, Sarah; Espeseth, Thomas; Fatouros-Bergman, Helena; Flyckt, Lena; Franke, Barbara; Frei, Oleksandr; Gelao, Barbara; Harbo, Hanne Flinstad; Hartman, Catharina A.; Håberg, Asta; Heslenfeld, Dirk; Hoekstra, Pieter J.; Høgestøl, Einar August; Jonassen, Rune; Jönsson, Erik Gunnar; Kirsch, Peter; Kloszewska, Iwona; Lagerberg, Trine Vik; Landrø, Nils Inge; Le Hellard, Stephanie; Lesch, Klaus-Peter; Maglanoc, Luigi Angelo; Malt, Ulrik Fredrik; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Moberget, Torgeir; Nordvik, Jan Egil; Nyberg, Lars; O`Connell, Kevin; Oosterlaan, Jaap; Papalino, Marco; Papassotiropoulos, Andreas; Pauli, Paul; Pergola, Giulio; Persson, Karin Ester Torun; de Quervain, Dominique; Reif, Andreas; Rokicki, Jaroslav; Van Rooij, Daan; Shadrin, Alexey A.; Schmidt, André; Schwarz, Emanuel; Selbæk, Geir; Sowa, Piotr; Soininen, Hilkka; Steen, Vidar Martin; Vellas, Bruno; Tsolaki, Magda; Wang, Lei; Westman, Eric; Ziegler, Georg C.; Zink, Mathias; Andreassen, Ole Andreas; Westlye, Lars Tjelta & Kaufmann, Tobias (2020). The genetic architecture of human brainstem structures and their involvement in common brain disorders. Nature Communications.  ISSN 2041-1723.  11 . doi: 10.1038/s41467-020-17376-1 Full text in Research Archive. Show summary

  Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson’s disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders.

• Engen, Magnus Johan; Lyngstad, Siv Hege; Ueland, Torill; Simonsen, Carmen Elisabeth; Vaskinn, Anja; Smeland, Olav Bjerkehagen; Bettella, Francesco; Lagerberg, Trine Vik; Djurovic, Srdjan; Andreassen, Ole Andreas & Melle, Ingrid (2020). Polygenic scores for schizophrenia and general cognitive ability: associations with six cognitive domains, premorbid intelligence, and cognitive composite score in individuals with a psychotic disorder and in healthy controls. Translational Psychiatry.  ISSN 2158-3188.  10:416, s 1- 9 . doi: 10.1038/s41398-020-01094-9 Full text in Research Archive.
• Feyer, Frida Karine; Andersson, Stein; Büchmann, Camilla Bakkalia; Melle, Ingrid; Andreassen, Ole Andreas & Vaskinn, Anja (2020). Social perception predicts awareness of illness in persons with schizophrenia. Journal of Nervous and Mental Disease.  ISSN 0022-3018.  208(9), s 701- 705 . doi: 10.1097/NMD.0000000000001185 Full text in Research Archive.
• Grasby, Katrina L.; Jahanshad, Neda; Painter, Jodie N; Colodro-Conde, Lucía; Bralten, Janita; Hibar, DP; Lind, Penelope A.; Pizzagalli, Fabrizio; Ching, Christopher R.K.; McMahon, Mary Agnes B.; Shatokhina, Natalia; Zsembik, Leo C.P.; Thomopoulos, Sophia I.; Zhu, Alyssa H.; Strike, Lachlan T.; Agartz, Ingrid; Alhusaini, Saud; Almeida, Marcio A.A.; Alnæs, Dag; Amlien, Inge Kasbohm; Doan, Nhat Trung; Gurholt, Tiril Pedersen; Kaufmann, Tobias; Richard, Geneviève; Sønderby, Ida Elken; van der Meer, Dennis; Wang, Yunpeng; Westlye, Lars Tjelta; Wolfers, Thomas; Brandt, Christine Lycke; Djurovic, Srdjan; Kolskår, Knut-Kristian; Le Hellard, Stephanie; Melle, Ingrid; Andreassen, Ole Andreas; Espeseth, Thomas; Jönsson, Erik Gunnar; Steen, Vidar Martin; Håberg, Asta; Trollor, Julian N.; Van Der Wee, Nic J.A.; Volzke, Henry; Walter, Henrik; Weber, Bernd; Weinberger, Daniel R.; Wright, Margaret J.; Zhou, Juan; Stein, Jason L.; Thompson, Paul M. & Medland, Sarah E. (2020). The genetic architecture of the human cerebral cortex. Science.  ISSN 0036-8075.  367(6484) . doi: 10.1126/science.aay6690 Full text in Research Archive. Show summary

  INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function.

• Haatveit, Beathe Christin; Mørch-Johnsen, Lynn; Alnæs, Dag; Engen, Magnus Johan; Lyngstad, Siv Hege; Færden, Ann; Agartz, Ingrid; Ueland, Torill & Melle, Ingrid (2020). Divergent relationship between brain structure and cognitive functioning in patients with prominent negative symptomatology. Psychiatry Research : Neuroimaging.  ISSN 0925-4927. . doi: 10.1016/j.pscychresns.2020.111233 Full text in Research Archive.
• Haukvik, Unn Kristin H.; Gurholt, Tiril Pedersen; Nerland, Stener; Elvsåshagen, Torbjørn; Akudjedu, Theophilus N.; Alda, Martin; Alnæs, Dag; Alonso-Lana, Silvia; Bauer, Jochen; Baune, Bernhard T.; Benedetti, Francesco; Berk, Michael; Bettella, Francesco; Bøen, Erlend; Bonnín, Caterina M.; Brambilla, Paolo; Canales-Rodríguez, Erick J.; Cannon, Dara M.; Caseras, Xavier; Dandash, Orwa; Dannlowski, Udo; Delvecchio, Giuseppe; Díaz-Zuluaga, Ana M.; van Erp, Theo G.M.; Fatjó-Vilas, Mar; Foley, Sonya F.; Förster, Katharina; Fullerton, Janice M.; Goikolea, Jose M.; Grotegerd, Dominik; Gruber, Oliver; Haarman, Bartholomeus C. M.; Haatveit, Beathe; Hajek, Tomas; Hallahan, Brian; Harris, Mathew; Hawkins, Emma L.; Howells, Fleur M.; Hülsmann, Carina; Jahanshad, Neda; Jørgensen, Kjetil Nordbø; Kircher, Tilo; Krämer, Bernd; Krug, Axel; Kuplicki, Rayus; Lagerberg, Trine Vik; Lancaster, Thomas M.; Lenroot, Rhoshel K.; Lonning, Vera Louise Hiorth; López-Jaramillo, Carlos; Malt, Ulrik Fredrik; McDonald, Colm; McIntosh, Andrew M.; McPhilemy, Genevieve; van der Meer, Dennis; Melle, Ingrid; Melloni, Elisa M. T.; Mitchell, Philip B.; Nabulsi, Leila; Nenadic, Igor; Oertel, Viola; Oldani, Lucio; Opel, Nils; Otaduy, Maria C. G.; Overs, Bronwyn; Pineda-Zapata, Julian A.; Pomarol-Clotet, Edith; Radua, Joaquim; Rauer, Lisa; Redlich, Ronny; Repple, Jonathan; Rive, Maria M.; Roberts, Gloria; Ruhe, Henricus G.; Salminen, Lauren E.; Salvador, Raymond; Sarró, Salvador; Savitz, Jonathan; Schene, Aart H.; Sim, Kang; Soeiro-de-Souza, Marcio G.; Stäblein, Michael; Stein, Dan J.; Stein, Frederike; Tamnes, Christian Krog; Temmingh, Henk S.; Thomopoulos, Sophia I.; Veltman, Dick J.; Vieta, Eduard; Waltemate, Lena; Westlye, Lars Tjelta; Whalley, Heather C.; Sämann, Philipp G.; Thompson, Paul M.; Ching, Christopher; Andreassen, Ole Andreas & Agartz, Ingrid (2020). In vivo hippocampal subfield volumes in bipolar disorder—A mega‐analysis from The Enhancing Neuro Imaging Genetics through Meta‐Analysis Bipolar Disorder Working Group. Human Brain Mapping.  ISSN 1065-9471.  s 1- 14 . doi: 10.1002/hbm.25249 Full text in Research Archive.

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• Andreassen, Ole Andreas; Malt, Ulrik Fredrik; Malt, Eva Albertsen & Melle, Ingrid (2020). Lærebok i psykiatri Basisversjon. Gyldendal Norsk Forlag A/S.  ISBN 978-82-05-52662-4.  519 s.

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• Gjerde, Priyanthi Borgen; Steen, Vidar Martin; Melle, Ingrid; Johnsen, Erik & Skrede, Silje (2020). Lipid effects during antipsychotic drug treatment and their relevance for clinical outcomes.

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