Early somatic trauma and gene effects on brain morphology in patients with schizophrenia and bipolar spectrum disorder

Prosjektnummer: 2011096
Ansvarlig person: Ingrid Agartz
Institusjon: Diakonhjemmet Sykehus AS
Prosjektkategori: Postdoktorstipend
Helsekategori: Mental Health
Forskningsaktivitet: 2. Aetiology

2014

In Vivo Hippocampal Subfield Volumes in Schizophrenia and Bipolar DisorderHippocampal dysfunction and volume reductions have been reported in patients with schizophrenia and bipolar disorder. The hippocampus consists of anatomically distinct subfields. We investigated to determine whether in vivo volumes of hippocampal subfields differ between clinical groups and healthy control subjects.BACKGROUND: The hippocampus is a limbic structure located in the medial temporal lobe. It is involved in verbal memory functions and other complex behaviors, including stress responses, emotions, sensorimotor integrations, and goal-directed activity, all of which may be disrupted in schizophrenia and bipolar disorder. Connectivity disruptions in local and external hippocampal circuits may be important to the formation of psychotic symptoms and thought content. Hippocampal dysfunction and volume reductions have been reported in patients with schizophrenia and bipolar disorder. The hippocampus consists of anatomically and functionally distinct subfields. We investigated to determine whether in vivo volumes of hippocampal subfields differ between clinical groups and healthy control subjects. If alterations in hippocampal subfield volumes differ between schizophrenia and bipolar disorder, this could point toward neurobiological mechanisms underlying the distinct clinical features of the two disorders. METHODS: Clinical examination and magnetic resonance imaging were performed in 702 subjects (patients with schizophrenia spectrum [n = 210; mean age, 32.0 ± 9.3 (SD) years; 59% were men], patients with bipolar spectrum [n = 192; mean age, 35.5 ± 11.5 years; 40% were men] and healthy control subjects [n = 300; mean age, 35.3 ± 9.9 years; 53% were men]). Hippocampal subfield volumes were estimated with FreeSurfer. General linear models were used to explore diagnostic differences in hippocampal subfield volumes, covarying for age, intracranial volume, and medication. Post hoc analyses of associations to psychosis symptoms (Positive and Negative Syndrome Scale) and cognitive function (verbal memory [California Verbal Learning Test, second edition] and IQ [Wechsler Abbreviated Scale of Intelligence]) were performed. RESULTS: Patient groups had smaller cornu ammonis (CA) subfields CA2/3 (left, p = 7.2 × 10-6; right, p = 2.3 × 10-6), CA4/dentate gyrus (left, p = 1.4 × 10-5; right, p = 2.3 × 10-6), subiculum (left, p = 3.7 × 10-6; right, p = 2.8 × 10-8), and right CA1 (p = .006) volumes than healthy control subjects, but smaller presubiculum volumes were found only in patients with schizophrenia (left, p = 6.7 × 10-5; right, p = 1.6 × 10-7). Patients with schizophrenia had smaller subiculum (left, p = .035; right, p = .031) and right presubiculum (p = .002) volumes than patients with bipolar disorder. Smaller subiculum volumes were related to poorer verbal memory in patients with bipolar disorder and healthy control subjects and to negative symptoms in patients with schizophrenia. CONCLUSIONS: The main findings were smaller CA2/3, CA4/DG, subiculum, and right CA1 subfield volumes in schizophrenia and bipolar disorder compared with healthy controls, with distinctly smaller subiculum and presubiculum in patients with schizophrenia compared with bipolar disorder. Although hippocampal subfield volume reductions are found in both patients with schizophrenia and bipolar disorder, the magnitude of reduction is greater in schizophrenia, particularly in the hippocampal outflow regions presubiculum and subiculum. Further studies exploring the pathophysiologic mechanisms that underlie associations between the subicular volume reductions and functional outcome in schizophrenia and bipolar disorder are warranted. This study will be followed by studies investigating whether a history of early somatic trauma (obstetric complications) impact on these findings.

2013

Early trauma, gene variants and brain structure in psychosisFrom MRI post-processing techniques, medical birth registry data, and a large sample of patients with psychosis disorders, we investigate relationships between early trauma and adult brain structure, which is abnormal in these disorders. We here report pre- and perinatal hypoxia to be associated with hippocampus/amygdala volume in bipolar disorder.During the year 2013, as part of a postdoctoral project, Dr. Unn Kristin Haukvik has studied how a history of hypoxia-related obstetric complications (OCs) are associated with brain structure anatomy in adult patients who suffer from bipolar spectrum disorders (Haukvik et al, Psychol Med. 2013). Our, as well as other, research groups have previously shown that in patients with schizophrenia or bipolar disorder there are changes in anatomical brain structure volumes, such as larger lateral ventricles and smaller hippocampus volumes and reduced subcortical structures. From epidemiological studies, it is known that pre- and perinatal adversities may increase the risk for developing schizophrenia and bipolar disorder. That hypoxia-related OCs are related with brain structure changes in schizophrenia have also been demonstrated, but the importance of pre- or perinatal hypoxia to brain anatomy in bipolar disorder is unknown. The subjects were all partaking in the TOP-project (Thematic Organized Research Project) at the University of Oslo with participating psychiatric hospitals and clinics in the Oslo region, Norway. Data on clinical examinations were obtained from the TOP-database. Birth and pregnancy data were obtained from the Medical Birth Registry of Norway. The sample included 219 adults, of which 79 were patients with a DSM-IV diagnosis of bipolar disorder (age 29.4 years, s.d. = 11.8 years, 39% male) and 140 were healthy controls (age 30.8 years, s.d. = 12.0 years, 53% male). All subjects were scanned using 1.5 Tesla magnetic resonance imaging (MRI). The MR scans were segmented using FreeSurfer software suite. Severe hypoxia-related OCs throughout pregnancy/birth and perinatal asphyxia were each studied in relation to a priori selected brain volumes (hippocampus, lateral ventricles and amygdala), using linear regression models covarying for age, sex, medication use and intracranial volume. Multiple comparison adjustment was applied. The results showed that perinatal asphyxia was associated with smaller left amygdala volume (t = -2.59, p = 0.012) in bipolar disorder patients, but not in healthy controls. Patients with psychotic bipolar disorder showed distinct associations between perinatal asphyxia and smaller left amygdala volume (t = -2.69, p = 0.010), whereas patients with non-psychotic bipolar disorder showed smaller right hippocampal volumes related to both perinatal asphyxia (t = -2.60, p = 0.015) and severe OCs (t = -3.25, p = 0.003). No associations between asphyxia or severe OCs and the lateral ventricles were found. We conclude that having experienced pre- and perinatal hypoxia-related OCs is associated with brain morphometry in bipolar disorder in adulthood, with specific patterns in patients with psychotic versus non-psychotic illness.

2012

Early trauma, gene variants and brain structure in psychosisBy using advanced MRI post-processing techniques, medical birth registry data, and a large sample of patients with psychosis spectrum disorders, we study how pre- or perinatal trauma is related with adult brain structure, known to be abnormal in schizophrenia and bipolar disorder, and if any such relationships are modified by genes.It is recognized that both environmental and genetic factors increase risk of schizophrenia (SCZ) and bipolar disorder (BD). Pre- and perinatal complications (OCs) increase risk for both SCZ and BD, and inherent features e.g. hypoxia, can regulate gene expression, and thus affect neuronal migration that may be disturbed in the severe psychotic diseases. By using advanced MRI post-processing techniques, medical birth registry data, and a large sample of patients with severe mental illness, we study how early trauma e.g. OCs affect brain structure, known to be abnormal in SCZ and BP, and how such associations are modified by genes. Cortical area and thickness follow different neurodevelopmental trajectories and have different prenatal migration patterns. During a 6 month visiting scholar period at the University of California San Diego, an advanced MRI post processing method by which cortical area and thickness are estimated with submillimetre resolution across the whole cortex was applied to MR scans from patients with psychosis spectrum (n=359, including patients with SCZ (n=90), BP (n=79,) or other psychosis (n=40), and healthy controls (n=140)) from the Norwegian TOP (Tematisk Område Psykoser) Study. The results show that within the normal birth weight (BW) range there is a linear (positive) correlation between birth weight and adult cortical surface area in the patients as well as in the healthy controls. The results have now been replicated in an independent sample and are expected to have a high impact when published. There are no associations to cortical thickness which fits with the understanding that cortical area and thickness follow distinct developmental trajectories. A diagnosis of psychosis is more strongly related to cortical thinning suggesting that reduction of cortical area and thickness reflect different pathophysiological mechanisms underlying psychotic disorders. Because low BW reflects an array of OCs, e.g. hypoxia, prematurity, and intrauterine growth retardation, normal BW variation is an indirect measure of both severe and subtle prenatal adversities. Our findings indicate that subtle, as well as severe, disturbances in neurodevelopment may have lasting effects on cortical anatomy, and that such effects are independent of a diagnosis of psychosis. Whether the smaller cortical surface area reflecting the lower BW found in SCZ interacts with other risk factors for developing psychosis is a topic for future research. In collaboration with researchers at Karolinska Institutet, we now test a model of gene x environment interaction on schizophrenia risk and brain structure. Based on results from genome wide association studies from large samples of SCZ and healthy subjects a polygenic risk score (PRS) is calculated for each individual. Using PRS, we will study if relationships between OCs and brain structure are modified by genetic risk. This may further increase our knowledge on how early trauma relate to the brain abnormalities found in psychotic disorders. We conclude that cortical area appears to be a general, rather than a diagnosis-specific, marker of early neurodevelopment, with a dose-response association to normal birth weight variation. This is of importance to the understanding of brain pathology in psychotic disorders as well as normal brain development.

2011

Tidig skada og geneffekt på hjärnan vid psykossjukdom.Postdoktor-projekt som behandlar tidigt somatiskt trauma (skadlig påverkan under fosterlivet och förlossning) och genetiska effekter, separat eller i samklang, som påverkar hjärnan och har betydelse för utvecklandet av psykossjukdom (schizofreni och bipolärt syndrom).Dr. Unn Haukvik, utdannet lege med klinisk erfaring av psykiatri, tillträdde postdocstilling finansiert av HSØ i august 2011. Under hösten 2011 har hon färdigställt en vetenskaplig artikel som har publicerats i den internationella tidskriften Psychological Medicine. I denna studien visar hon att en reduktion av hjärnbarkens veckning (gyrificering), som på MR-bilder observeras i ett område i hjärnan vid namn pars triangularis, är specifikt associert med en ökad förekomst av obstetriska komplikationer som individen utsatts för tidigare i livet eller under fosterstadiet. Detta iakttages både hos patienter och friska kontrollpersoner. Uppgifterna om obstetriske komplikationer har erhållits genom att skatta information från kliniska förlossningsjournaler från svenske patienter som Dr. Haukvik studerade i sitt doktorgradsarbete. Hon har under hösten även arbetat med att skatta födelsedata fra Nyfødtmedisinsk kvalitetsregister i Norge, enligt en speciell skattningsskala, för patienter som deltager i våra hjernemorfologiska studier i TOP-projektet. Hon finner att fødelsevikt är korrelerat med storleken av hjärnytan, och att detta gäller även innanför det "normala" eller förväntade spannet av fødelsevikt. Vi har nyligen rapporterat att hjärnytan är minskad i vissa områden av hjärnan vid schizofreni och har utvecklat hypoteser att detta skulle kunna bero på störning i anläggningen av hjärnbarken. Anläggningen äger rum i fosterlivet och står under genetisk styrning men utvecklingen kan påverkas av yttre faktorer som infektion, malnutrition eller trauma. Normalt brukar man finna påverkansidikatorer i förhållande till diagnos i epidemiologiske studier men det er muligt att vi påvisat ett betydelsefullt samband i ett kliniskt material för vilket vi har hjernebilder med mål på hjärnans neuroanatomi. Dr. Haukvik har vidare sammanställt MR-data att benyttes under forskningsvistelse i USA planerad for förste halvan av 2012. Hon har också författat en ansökan till HSØ om stipendiatprojekt avseende studier av tidigt trauma och geneffekter på hjernen vid ungdomspsykos. Denna har glädjande nog beviljats.

Vitenskapelige artikler

Haukvik UK, Westlye LT, Mørch-Johnsen L, Jørgensen KN, Lange EH, Dale AM, Melle I, Andreassen OA, Agartz I

In vivo hippocampal subfield volumes in schizophrenia and bipolar disorder.

Biol Psychiatry 2015 Mar 15;77(6):581-8. Epub 2014 jul 3

PMID: 25127742

Aas Monica, Haukvik Unn K, Djurovic Srdjan, Tesli Martin, Athanasiu Lavinia, Bjella Thomas, Hansson Lars, Cattaneo Annamaria, Agartz Ingrid, Andreassen Ole A, Melle Ingrid

Interplay between childhood trauma and BDNF val66met variants on blood BDNF mRNA levels and on hippocampus subfields volumes in schizophrenia spectrum and bipolar disorders.

J Psychiatr Res 2014 Dec;59():14-21. Epub 2014 aug 30

PMID: 25246365

Dieset I, Haukvik UK, Melle I, Røssberg JI, Ueland T, Hope S, Dale AM, Djurovic S, Aukrust P, Agartz I, Andreassen OA

Association between altered brain morphology and elevated peripheral endothelial markers--implications for psychotic disorders.

Schizophr Res 2015 Feb;161(2-3):222-8. Epub 2014 nov 27

PMID: 25433965

Nesvåg Ragnar, Schaer Marie, Haukvik Unn K, Westlye Lars T, Rimol Lars M, Lange Elisabeth H, Hartberg Cecilie B, Ottet Marie-Christine, Melle Ingrid, Andreassen Ole A, Jönsson Erik G, Agartz Ingrid, Eliez Stephan

Reduced brain cortical folding in schizophrenia revealed in two independent samples.

Schizophr Res 2014 Feb;152(2-3):333-8. Epub 2013 des 22

PMID: 24365403

Lange Elisabeth Heffermehl, Nesvåg Ragnar, Ringen Petter Andreas, Hartberg Cecilie Bhandari, Haukvik Unn Kristin, Andreassen Ole Andreas, Melle Ingrid, Agartz Ingrid

One year follow-up of alcohol and illicit substance use in first-episode psychosis: does gender matter?

Compr Psychiatry 2014 Feb;55(2):274-82. Epub 2013 okt 19

PMID: 24262129

Thompson Paul M, Stein Jason L, Medland Sarah E, Hibar Derrek P, Vasquez Alejandro Arias, Renteria Miguel E, Toro Roberto, Jahanshad Neda, Schumann Gunter, Franke Barbara, Wright Margaret J, Martin Nicholas G, Agartz Ingrid, Alda Martin, Alhusaini Saud, Almasy Laura, Almeida Jorge, Alpert Kathryn, Andreasen Nancy C, Andreassen Ole A, Apostolova Liana G, Appel Katja, Armstrong Nicola J, Aribisala Benjamin, Bastin Mark E, Bauer Michael, Bearden Carrie E, Bergmann Orjan, Binder Elisabeth B, Blangero John, Bockholt Henry J, Bøen Erlend, Bois Catherine, Boomsma Dorret I, Booth Tom, Bowman Ian J, Bralten Janita, Brouwer Rachel M, Brunner Han G, Brohawn David G, Buckner Randy L, Buitelaar Jan, Bulayeva Kazima, Bustillo Juan R, Calhoun Vince D, Cannon Dara M, Cantor Rita M, Carless Melanie A, Caseras Xavier, Cavalleri Gianpiero L, Chakravarty M Mallar, Chang Kiki D, Ching Christopher R K, Christoforou Andrea, Cichon Sven, Clark Vincent P, Conrod Patricia, Coppola Giovanni, Crespo-Facorro Benedicto, Curran Joanne E, Czisch Michael, Deary Ian J, de Geus Eco J C, den Braber Anouk, Delvecchio Giuseppe, Depondt Chantal, de Haan Lieuwe, de Zubicaray Greig I, Dima Danai, Dimitrova Rali, Djurovic Srdjan, Dong Hongwei, Donohoe Gary, Duggirala Ravindranath, Dyer Thomas D, Ehrlich Stefan, Ekman Carl Johan, Elvsåshagen Torbjørn, Emsell Louise, Erk Susanne, Espeseth Thomas, Fagerness Jesen, Fears Scott, Fedko Iryna, Fernández Guillén, Fisher Simon E, Foroud Tatiana, Fox Peter T, Francks Clyde, Frangou Sophia, Frey Eva Maria, Frodl Thomas, Frouin Vincent, Garavan Hugh, Giddaluru Sudheer, Glahn David C, Godlewska Beata, Goldstein Rita Z, Gollub Randy L, Grabe Hans J, Grimm Oliver, Gruber Oliver, Guadalupe Tulio, Gur Raquel E, Gur Ruben C, Göring Harald H H, Hagenaars Saskia, Hajek Tomas, Hall Geoffrey B, Hall Jeremy, Hardy John, Hartman Catharina A, Hass Johanna, Hatton Sean N, Haukvik Unn K, Hegenscheid Katrin, Heinz Andreas, Hickie Ian B, Ho Beng-Choon, Hoehn David, Hoekstra Pieter J, Hollinshead Marisa, Holmes Avram J, Homuth Georg, Hoogman Martine, Hong L Elliot, Hosten Norbert, Hottenga Jouke-Jan, Hulshoff Pol Hilleke E, Hwang Kristy S, Jack Clifford R, Jenkinson Mark, Johnston Caroline, Jönsson Erik G, Kahn René S, Kasperaviciute Dalia, Kelly Sinead, Kim Sungeun, Kochunov Peter, Koenders Laura, Krämer Bernd, Kwok John B J, Lagopoulos Jim, Laje Gonzalo, Landen Mikael, Landman Bennett A, Lauriello John, Lawrie Stephen M, Lee Phil H, Le Hellard Stephanie, Lemaître Herve, Leonardo Cassandra D, Li Chiang-Shan, Liberg Benny, Liewald David C, Liu Xinmin, Lopez Lorna M, Loth Eva, Lourdusamy Anbarasu, Luciano Michelle, Macciardi Fabio, Machielsen Marise W J, Macqueen Glenda M, Malt Ulrik F, Mandl René, Manoach Dara S, Martinot Jean-Luc, Matarin Mar, Mather Karen A, Mattheisen Manuel, Mattingsdal Morten, Meyer-Lindenberg Andreas, McDonald Colm, McIntosh Andrew M, McMahon Francis J, McMahon Katie L, Meisenzahl Eva, Melle Ingrid, Milaneschi Yuri, Mohnke Sebastian, Montgomery Grant W, Morris Derek W, Moses Eric K, Mueller Bryon A, Muñoz Maniega Susana, Mühleisen Thomas W, Müller-Myhsok Bertram, Mwangi Benson, Nauck Matthias, Nho Kwangsik, Nichols Thomas E, Nilsson Lars-Göran, Nugent Allison C, Nyberg Lars, Olvera Rene L, Oosterlaan Jaap, Ophoff Roel A, Pandolfo Massimo, Papalampropoulou-Tsiridou Melina, Papmeyer Martina, Paus Tomas, Pausova Zdenka, Pearlson Godfrey D, Penninx Brenda W, Peterson Charles P, Pfennig Andrea, Phillips Mary, Pike G Bruce, Poline Jean-Baptiste, Potkin Steven G, Pütz Benno, Ramasamy Adaikalavan, Rasmussen Jerod, Rietschel Marcella, Rijpkema Mark, Risacher Shannon L, Roffman Joshua L, Roiz-Santiañez Roberto, Romanczuk-Seiferth Nina, Rose Emma J, Royle Natalie A, Rujescu Dan, Ryten Mina, Sachdev Perminder S, Salami Alireza, Satterthwaite Theodore D, Savitz Jonathan, Saykin Andrew J, Scanlon Cathy, Schmaal Lianne, Schnack Hugo G, Schork Andrew J, Schulz S Charles, Schür Remmelt, Seidman Larry, Shen Li, Shoemaker Jody M, Simmons Andrew, Sisodiya Sanjay M, Smith Colin, Smoller Jordan W, Soares Jair C, Sponheim Scott R, Sprooten Emma, Starr John M, Steen Vidar M, Strakowski Stephen, Strike Lachlan, Sussmann Jessika, Sämann Philipp G, Teumer Alexander, Toga Arthur W, Tordesillas-Gutierrez Diana, Trabzuni Daniah, Trost Sarah, Turner Jessica, Van den Heuvel Martijn, van der Wee Nic J, van Eijk Kristel, van Erp Theo G M, Van Haren Neeltje E M, van 't Ent Dennis, van Tol Marie-Jose, Valdés Hernández Maria C, Veltman Dick J, Versace Amelia, Völzke Henry, Walker Robert, Walter Henrik, Wang Lei, Wardlaw Joanna M, Weale Michael E, Weiner Michael W, Wen Wei, Westlye Lars T, Whalley Heather C, Whelan Christopher D, White Tonya, Winkler Anderson M, Wittfeld Katharina, Woldehawariat Girma, Wolf Christiane, Zilles David, Zwiers Marcel P, Thalamuthu Anbupalam, Schofield Peter R, Freimer Nelson B, Lawrence Natalia S, Drevets Wayne, Alzheimer’s Disease Neuroimaging Initiative, EPIGEN Consortium, IMAGEN Consortium, Saguenay Youth Study (SYS) Group

The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data.

Brain Imaging Behav 2014 Jun;8(2):153-82.

PMID: 24399358

Aas Monica, Haukvik Unn K, Djurovic Srdjan, Bergmann Ørjan, Athanasiu Lavinia, Tesli Martin S, Hellvin Tone, Steen Nils Eiel, Agartz Ingrid, Lorentzen Steinar, Sundet Kjetil, Andreassen Ole A, Melle Ingrid

BDNF val66met modulates the association between childhood trauma, cognitive and brain abnormalities in psychoses.

Prog Neuropsychopharmacol Biol Psychiatry 2013 Oct 1;46():181-8. Epub 2013 jul 19

PMID: 23876786

Haukvik U K, McNeil T, Lange E H, Melle I, Dale A M, Andreassen O A, Agartz I

Pre- and perinatal hypoxia associated with hippocampus/amygdala volume in bipolar disorder.

Psychol Med 2014 Apr;44(5):975-85. Epub 2013 jun 27

PMID: 23803260

Bergmann Orjan, Haukvik Unn K, Brown Andrew A, Rimol Lars M, Hartberg Cecilie B, Athanasiu Lavinia, Melle Ingrid, Djurovic Srdjan, Andreassen Ole A, Dale Anders M, Agartz Ingrid

ZNF804A and cortical thickness in schizophrenia and bipolar disorder.

Psychiatry Res 2013 May 30;212(2):154-7. Epub 2013 apr 4

PMID: 23562677

Haukvik Unn K, Rimol Lars M, Roddey J Cooper, Hartberg Cecilie B, Lange Elisabeth H, Vaskinn Anja, Melle Ingrid, Andreassen Ole A, Dale Anders, Agartz Ingrid

Normal birth weight variation is related to cortical morphology across the psychosis spectrum.

Schizophr Bull 2014 Mar;40(2):410-9. Epub 2013 feb 18

PMID: 23419977

Nesvåg Ragnar, Bergmann Ørjan, Rimol Lars M, Lange Elisabeth H, Haukvik Unn K, Hartberg Cecilie B, Fagerberg Thomas, Söderman Erik, Jönsson Erik G, Agartz Ingrid

A 5-year follow-up study of brain cortical and subcortical abnormalities in a schizophrenia cohort.

Schizophr Res 2012 Dec;142(1-3):209-16. Epub 2012 okt 30

PMID: 23116883

Wirgenes K V, Sønderby I E, Haukvik U K, Mattingsdal M, Tesli M, Athanasiu L, Sundet K, Røssberg J I, Dale A M, Brown A A, Agartz I, Melle I, Djurovic S, Andreassen O A

TCF4 sequence variants and mRNA levels are associated with neurodevelopmental characteristics in psychotic disorders.

Transl Psychiatry 2012;2():e112. Epub 2012 mai 8

PMID: 22832956

Rimol Lars M, Nesvåg Ragnar, Hagler Don J, Bergmann Orjan, Fennema-Notestine Christine, Hartberg Cecilie B, Haukvik Unn K, Lange Elisabeth, Pung Chris J, Server Andres, Melle Ingrid, Andreassen Ole A, Agartz Ingrid, Dale Anders M

Cortical volume, surface area, and thickness in schizophrenia and bipolar disorder.

Biol Psychiatry 2012 Mar;71(6):552-60. Epub 2012 jan 26

PMID: 22281121

Haukvik U K, Schaer M, Nesvåg R, McNeil T, Hartberg C B, Jönsson E G, Eliez S, Agartz I

Cortical folding in Broca's area relates to obstetric complications in schizophrenia patients and healthy controls.

Psychol Med 2012 Jun;42(6):1329-37. Epub 2011 okt 26

PMID: 22029970

Hartberg C B, Sundet K, Rimol L M, Haukvik U K, Lange E H, Nesvåg R, Dale A M, Melle I, Andreassen O A, Agartz I

Brain cortical thickness and surface area correlates of neurocognitive performance in patients with schizophrenia, bipolar disorder, and healthy adults.

J Int Neuropsychol Soc 2011 Nov;17(6):1080-93. Epub 2011 okt 3

PMID: 22013998

Hartberg Cecilie B, Sundet Kjetil, Rimol Lars M, Haukvik Unn K, Lange Elisabeth H, Nesvåg Ragnar, Melle Ingrid, Andreassen Ole A, Agartz Ingrid

Subcortical brain volumes relate to neurocognition in schizophrenia and bipolar disorder and healthy controls.

Prog Neuropsychopharmacol Biol Psychiatry 2011 Jun;35(4):1122-30. Epub 2011 mar 30

PMID: 21457744

Bakken Trygve E, Bloss Cinnamon S, Roddey J Cooper, Joyner Alexander H, Rimol Lars M, Djurovic Srdjan, Melle Ingrid, Sundet Kjetil, Agartz Ingrid, Andreassen Ole A, Dale Anders M, Schork Nicholas J

Association of genetic variants on 15q12 with cortical thickness and cognition in schizophrenia.

Arch Gen Psychiatry 2011 Aug;68(8):781-90.

PMID: 21810643

Agartz Ingrid, Brown Andrew Anand, Rimol Lars M, Hartberg Cecilie B, Dale Anders M, Melle Ingrid, Djurovic Srdjan, Andreassen Ole A

Common sequence variants in the major histocompatibility complex region associate with cerebral ventricular size in schizophrenia.

Biol Psychiatry 2011 Oct;70(7):696-8. Epub 2011 apr 22

PMID: 21514568

Kähler Anna K, Djurovic Srdjan, Rimol Lars M, Brown Andrew Anand, Athanasiu Lavinia, Jönsson Erik G, Hansen Thomas, Gústafsson Omar, Hall Håkan, Giegling Ina, Muglia Pierandrea, Cichon Sven, Rietschel Marcella, Pietiläinen Olli P H, Peltonen Leena, Bramon Elvira, Collier David, St Clair David, Sigurdsson Engilbert, Petursson Hannes, Rujescu Dan, Melle Ingrid, Werge Thomas, Steen Vidar M, Dale Anders M, Matthews Russell T, Agartz Ingrid, Andreassen Ole A

Candidate gene analysis of the human natural killer-1 carbohydrate pathway and perineuronal nets in schizophrenia: B3GAT2 is associated with disease risk and cortical surface area.

Biol Psychiatry 2011 Jan;69(1):90-6. Epub 2010 okt 15

PMID: 20950796

Leblanc Marissa, Kulle Bettina, Sundet Kjetil, Agartz Ingrid, Melle Ingrid, Djurovic Srdjan, Frigessi Arnoldo, Andreassen Ole A

Genome-wide study identifies PTPRO and WDR72 and FOXQ1-SUMO1P1 interaction associated with neurocognitive function.

J Psychiatr Res 2012 Feb;46(2):271-8. Epub 2011 nov 29

PMID: 22126837

Tesli Martin, Koefoed Pernille, Athanasiu Lavinia, Mattingsdal Morten, Gustafsson Omar, Agartz Ingrid, Rimol Lars M, Brown Andrew, Wirgenes Katrine V, Smorr Lisa-Lena, Kähler Anna K, Werge Thomas, Mors Ole, Mellerup Erling, Jönsson Erik G, Melle Ingrid, Morken Gunnar, Djurovic Srdjan, Andreassen Ole A

Association analysis of ANK3 gene variants in nordic bipolar disorder and schizophrenia case-control samples.

Am J Med Genet B Neuropsychiatr Genet 2011 Dec;156B(8):969-74. Epub 2011 okt 3

PMID: 21972176

Ripke Stephan, Sanders Alan R, Kendler Kenneth S, Levinson Douglas F, Sklar Pamela, Holmans Peter A, Lin Dan-Yu, Duan Jubao, Ophoff Roel A, Andreassen Ole A, Scolnick Edward, Cichon Sven, St Clair David, Corvin Aiden, Gurling Hugh, Werge Thomas, Rujescu Dan, Blackwood Douglas H R, Pato Carlos N, Malhotra Anil K, Purcell Shaun, Dudbridge Frank, Neale Benjamin M, Rossin Lizzy, Visscher Peter M, Posthuma Danielle, Ruderfer Douglas M, Fanous Ayman, Stefansson Hreinn, Steinberg Stacy, Mowry Bryan J, Golimbet Vera, De Hert Marc, Jönsson Erik G, Bitter István, Pietiläinen Olli P H, Collier David A, Tosato Sarah, Agartz Ingrid, Albus Margot, Alexander Madeline, Amdur Richard L, Amin Farooq, Bass Nicholas, Bergen Sarah E, Black Donald W, Børglum Anders D, Brown Matthew A, Bruggeman Richard, Buccola Nancy G, Byerley William F, Cahn Wiepke, Cantor Rita M, Carr Vaughan J, Catts Stanley V, Choudhury Khalid, Cloninger C Robert, Cormican Paul, Craddock Nicholas, Danoy Patrick A, Datta Susmita, de Haan Lieuwe, Demontis Ditte, Dikeos Dimitris, Djurovic Srdjan, Donnelly Peter, Donohoe Gary, Duong Linh, Dwyer Sarah, Fink-Jensen Anders, Freedman Robert, Freimer Nelson B, Friedl Marion, Georgieva Lyudmila, Giegling Ina, Gill Michael, Glenthøj Birte, Godard Stephanie, Hamshere Marian, Hansen Mark, Hansen Thomas, Hartmann Annette M, Henskens Frans A, Hougaard David M, Hultman Christina M, Ingason Andrés, Jablensky Assen V, Jakobsen Klaus D, Jay Maurice, Jürgens Gesche, Kahn René S, Keller Matthew C, Kenis Gunter, Kenny Elaine, Kim Yunjung, Kirov George K, Konnerth Heike, Konte Bettina, Krabbendam Lydia, Krasucki Robert, Lasseter Virginia K, Laurent Claudine, Lawrence Jacob, Lencz Todd, Lerer F Bernard, Liang Kung-Yee, Lichtenstein Paul, Lieberman Jeffrey A, Linszen Don H, Lönnqvist Jouko, Loughland Carmel M, Maclean Alan W, Maher Brion S, Maier Wolfgang, Mallet Jacques, Malloy Pat, Mattheisen Manuel, Mattingsdal Morten, McGhee Kevin A, McGrath John J, McIntosh Andrew, McLean Duncan E, McQuillin Andrew, Melle Ingrid, Michie Patricia T, Milanova Vihra, Morris Derek W, Mors Ole, Mortensen Preben B, Moskvina Valentina, Muglia Pierandrea, Myin-Germeys Inez, Nertney Deborah A, Nestadt Gerald, Nielsen Jimmi, Nikolov Ivan, Nordentoft Merete, Norton Nadine, Nöthen Markus M, O'Dushlaine Colm T, Olincy Ann, Olsen Line, O'Neill F Anthony, Orntoft Torben F, Owen Michael J, Pantelis Christos, Papadimitriou George, Pato Michele T, Peltonen Leena, Petursson Hannes, Pickard Ben, Pimm Jonathan, Pulver Ann E, Puri Vinay, Quested Digby, Quinn Emma M, Rasmussen Henrik B, Réthelyi János M, Ribble Robert, Rietschel Marcella, Riley Brien P, Ruggeri Mirella, Schall Ulrich, Schulze Thomas G, Schwab Sibylle G, Scott Rodney J, Shi Jianxin, Sigurdsson Engilbert, Silverman Jeremy M, Spencer Chris C A, Stefansson Kari, Strange Amy, Strengman Eric, Stroup T Scott, Suvisaari Jaana, Terenius Lars, Thirumalai Srinivasa, Thygesen Johan H, Timm Sally, Toncheva Draga, van den Oord Edwin, van Os Jim, van Winkel Ruud, Veldink Jan, Walsh Dermot, Wang August G, Wiersma Durk, Wildenauer Dieter B, Williams Hywel J, Williams Nigel M, Wormley Brandon, Zammit Stan, Sullivan Patrick F, O'Donovan Michael C, Daly Mark J, Gejman Pablo V, PubMed.ItemsChoiceType2[]

Genome-wide association study identifies five new schizophrenia loci.

Nat Genet 2011 Oct;43(10):969-76. Epub 2011 sep 18

PMID: 21926974

Hope Sigrun, Dieset Ingrid, Agartz Ingrid, Steen Nils E, Ueland Thor, Melle Ingrid, Aukrust Pål, Andreassen Ole A

Affective symptoms are associated with markers of inflammation and immune activation in bipolar disorders but not in schizophrenia.

J Psychiatr Res 2011 Dec;45(12):1608-16. Epub 2011 sep 1

PMID: 21889167

Steinberg Stacy, de Jong Simone, PubMed.ItemsChoiceType2[], Andreassen Ole A, Werge Thomas, Børglum Anders D, Mors Ole, Mortensen Preben B, Gustafsson Omar, Costas Javier, Pietiläinen Olli P H, Demontis Ditte, Papiol Sergi, Huttenlocher Johanna, Mattheisen Manuel, Breuer René, Vassos Evangelos, Giegling Ina, Fraser Gillian, Walker Nicholas, Tuulio-Henriksson Annamari, Suvisaari Jaana, Lönnqvist Jouko, Paunio Tiina, Agartz Ingrid, Melle Ingrid, Djurovic Srdjan, Strengman Eric, PubMed.ItemsChoiceType2[], Jürgens Gesche, Glenthøj Birte, Terenius Lars, Hougaard David M, Ørntoft Torben, Wiuf Carsten, Didriksen Michael, Hollegaard Mads V, Nordentoft Merete, van Winkel Ruud, Kenis Gunter, Abramova Lilia, Kaleda Vasily, Arrojo Manuel, Sanjuán Julio, Arango Celso, Sperling Swetlana, Rossner Moritz, Ribolsi Michele, Magni Valentina, Siracusano Alberto, Christiansen Claus, Kiemeney Lambertus A, Veldink Jan, van den Berg Leonard, Ingason Andres, Muglia Pierandrea, Murray Robin, Nöthen Markus M, Sigurdsson Engilbert, Petursson Hannes, Thorsteinsdottir Unnur, Kong Augustine, Rubino I Alex, De Hert Marc, Réthelyi János M, Bitter István, Jönsson Erik G, Golimbet Vera, Carracedo Angel, Ehrenreich Hannelore, Craddock Nick, Owen Michael J, O'Donovan Michael C, PubMed.ItemsChoiceType2[], Ruggeri Mirella, Tosato Sarah, Peltonen Leena, Ophoff Roel A, Collier David A, St Clair David, Rietschel Marcella, Cichon Sven, Stefansson Hreinn, Rujescu Dan, Stefansson Kari

Common variants at VRK2 and TCF4 conferring risk of schizophrenia.

Hum Mol Genet 2011 Oct;20(20):4076-81. Epub 2011 jul 26

PMID: 21791550

Rietschel M, Mattheisen M, Degenhardt F, eUtils.ItemsChoiceType2[], Mühleisen T W, Kirsch P, Esslinger C, Herms S, Demontis D, Steffens M, Strohmaier J, Haenisch B, Breuer R, Czerski P M, Giegling I, Strengman E, Schmael C, Mors O, Mortensen P B, Hougaard D M, Ørntoft T, Kapelski P, Priebe L, Basmanav F F, Forstner A J, Hoffman P, Meier S, Nikitopoulos J, Moebus S, Alexander M, Mössner R, Wichmann H -E, Schreiber S, Rivandeneira F, Hofman A, Uitterlinden A G, Wienker T F, Schumacher J, Hauser J, Maier W, Cantor R M, Erk S, Schulze T G, eUtils.ItemsChoiceType2[], Craddock N, Owen M J, O'Donovan M C, Børglum A D, Rujescu D, Walter H, Meyer-Lindenberg A, Nöthen N M, Ophoff R A, Cichon S

Association between genetic variation in a region on chromosome 11 and schizophrenia in large samples from Europe.

Mol Psychiatry 2012 Sep;17(9):906-17. Epub 2011 jul 12

PMID: 21747397

Olsen Line, Hansen Thomas, Djurovic Srdjan, Haastrup Eva, Albrecthsen Anders, Hoeffding Louise K E, Secher Anna, Gustafsson Omar, Jakobsen Klaus D, Nielsen Finn C, Ullum Henrik, Morken Gunnar, Agartz Ingrid, Melle Ingrid, Gether Ulrik, Andreassen Ole A, Werge Thomas

Copy number variations in affective disorders and meta-analysis.

Psychiatr Genet 2011 Dec;21(6):319-22.

PMID: 21451435

Håvik Bjarte, Le Hellard Stephanie, Rietschel Marcella, Lybæk Helle, Djurovic Srdjan, Mattheisen Manuel, Mühleisen Thomas W, Degenhardt Franziska, Priebe Lutz, Maier Wolfgang, Breuer Rene, Schulze Thomas G, Agartz Ingrid, Melle Ingrid, Hansen Thomas, Bramham Clive R, Nöthen Markus M, Stevens Beth, Werge Thomas, Andreassen Ole A, Cichon Sven, Steen Vidar M

The complement control-related genes CSMD1 and CSMD2 associate to schizophrenia.

Biol Psychiatry 2011 Jul;70(1):35-42. Epub 2011 mar 24

PMID: 21439553

Steen Nils Eiel, Methlie Paal, Lorentzen Steinar, Hope Sigrun, Barrett Elizabeth A, Larsson Sara, Mork Erlend, Almås Bjørg, Løvås Kristian, Agartz Ingrid, Melle Ingrid, Berg Jens P, Andreassen Ole A

Increased systemic cortisol metabolism in patients with schizophrenia and bipolar disorder: a mechanism for increased stress vulnerability?

J Clin Psychiatry 2011 Nov;72(11):1515-21. Epub 2011 feb 8

PMID: 21367348

Saetre Peter, Vares Maria, Werge Thomas, Andreassen Ole A, Arinami Tadao, Ishiguro Hiroki, Nanko Shinichiro, Tan Ene Choo, Han Doug Hyun, Roffman Joshua L, Muntjewerff Jan-Willem, Jagodzinski Pawel P, Kempisty Bartosz, Hauser Joanna, Vilella Elisabet, Betcheva Elitza, Nakamura Yusuke, Regland Björn, Agartz Ingrid, Hall Håkan, Terenius Lars, Jönsson Erik G

Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and age of onset in schizophrenia: a combined analysis of independent samples.

Am J Med Genet B Neuropsychiatr Genet 2011 Mar;156(2):215-24. Epub 2011 jan 13

PMID: 21302350

Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and age of onset in schizophrenia: A combined analysis of independent samples.

Am J Med Genet B Neuropsychiatr Genet 2011 Jan. Epub 2011 jan 13

PMID: 21234904

Doktorgrader

Cecilie Bhandari Hartberg

Anatomical brain structure and the relationship with neurocognitive functioning.

Disputert:: september 2011
Hovedveileder:: Ingrid Agartz

Unn Kristin Haukvik

Effects of obstetric complications on brain structure in schizophrenia

Disputert:: januar 2011
Hovedveileder:: Ingrid Agartz

Deltagere

Kjetil Nordbø Jørgensen Doktorgradsstipendiat
Lynn Mørch-Johnsen Doktorgradsstipendiat
Ole Andreas Andreassen Forskningsgruppeleder
Ingrid Melle Forskningsgruppeleder
Ingrid Agartz Prosjektleder
Elisabeth Lange Doktorgradsstipendiat
Lars Tjelta Westlye Prosjektdeltaker
Unn Kristin H. Haukvik Postdoktorstipendiat

eRapport er utarbeidet av Sølvi Lerfald og Reidar Thorstensen, Regionalt kompetansesenter for klinisk forskning, Helse Vest RHF, og videreutvikles av de fire RHF-ene i fellesskap, med støtte fra Helse Vest IKT

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