Title: Neurophysiological brain responses and school performance in adolescents at familial/genetic risk of severe mental illness
Date: 5^th July 2024, 09.00 AM
Place: Aarhus University Hospital, Auditorium G206-145

The defence is public, in English and expected to last 2 hours.
After the defence, Psychosis Research Unit will host a reception in front of the auditorium.

ALL ARE WELCOME

About the PhD thesis:

Schizophrenia (SZ) and bipolar disorder (BD) are severe mental disorders with a strong genetic component. While genetic studies have identified molecular pathways associated with SZ and BD, understanding how these relate to symptoms, cognitive processes and neurobiology remains challenging. To address this gap, our studies examine how familial and genetic risk for SZ and BD influence adolescent neurophysiological brain responses. Additionally, we investigate the impact of genetic risk of SZ and BD (and other disorders) on school performance in adolescence.

We acquired and analysed magnetoencephalographic (MEG) data from adolescents in The Danish High Risk and Resilience Study VIA, a register-based cohort. Using the roving auditory paradigm and 40 Hz auditory steady-state response (ASSR), known for revealing impairments in SZ and BD patients, we investigated the effects of familial and genetic (polygenic) risk of SZ and BD on auditory responses and cortical circuits using dynamic causal modelling (DCM). Additionally, we determined the association between polygenic risk of mental disorders and subject-specific school grades obtained in adolescence and early adulthood using nationwide-representative cohort data. To complement these studies, we conducted a meta-analysis of previous 40 Hz ASSR studies in patients with BD and a quality development project on the use of neurophysiological assessments (electroencephalography) in psychiatric settings.

Conventional MEG analysis revealed intact responses in adolescents at familial high risk of SZ or BD, suggesting that substantial impairments seen in patients and adult relatives depend on a fuller maturation of cortical circuits. DCM analyses, however, revealed changes in effective connectivity related to both familial and polygenic risk of SZ and BD, indicating potential for early detection of aberrant neurophysiology. Polygenic risk of SZ was associated with lower mathematics grades, but higher language grades, while polygenic risk of BD was associated with higher grades in both subjects, suggesting that genetic risk of SZ and BD can manifest both as impairments and strengths. In the clinical quality development project, EEG showed limited diagnostic utility in psychiatric settings with current methods. Despite the clinical potential of novel neurophysiological biomarkers, further research is needed before implementation.

Opponents:

• Marta Garrido, PhD, Professor of Psychology, Melbourne School of Psychological Sciences, The University of Melbourne, Australia.
• Juanita Todd, Professor of Psychology, The University of Newcastle, Australia.
• Charlotte Ulrikka Rask, Clinical Professor, Psychiatric Hospital for Children and Adolescents, AUH – Psychiatry (Chairperson of assessment committee)

Supervisors:

• Yury Shtyrov, Professor, CFIN, Aarhus University
• Martin Dietz, Assistant Professor, CFIN, Aarhus University
• Ole Mors, Professor, Psychosis Research Unit, Aarhus University Hospital Psychiatry
• Karl Friston, Professor, Wellcome Centre for Human Neuroimaging, Institute of Neurology, University College London

Contact:

For more information, please contact

Oskar Hougaard Jefsen
oskar.jefsen@clin.au.dk
+45 30 11 20 66

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DANISH:

Titel: Neurophysiological brain responses and school performance in adolescents at familial/genetic risk of severe mental illness
Tid: 5. juli 2024, kl. 09.00
Sted: Aarhus Universitetshospital, Auditorium G206-145

Forsvaret er offentligt, foregår på engelsk og forventes at vare ca. 2 timer.
Efter forsvaret er Forskningsenhed for Psykoser vært ved en reception foran auditoriet.

ALLE ER VELKOMNE

Om ph.d.-afhandlingen:

Skizofreni (SZ) og bipolar affektiv sindslidelse (BAS) er svære psykiske sygdomme med høj arvelighed. Selvom genetiske studier har identificeret molekylære mekanismer associateret med SZ og BD er det fortsat svært at koble disse til symptomer, kognitive processer, og neurobiologi. Derfor undersøgte vi, hvordan familiær og genetisk risiko for SZ or BAS påvirker neurofysiologiske hjerneresponser samt effekterne af genetisk risiko for SZ or BAS (og andre lidelser) på skolekarakterer blandt unge.

Vi optog og analyserede magnetoencefalografiske data fra unge deltagere i The Danish High-Risk and Resilience Study – VIA. Vi anvendte roving auditory oddball- og 40 Hz auditory steady-state (ASSR) paradigmer, som sædvanligvis viser svækkelser i patienter med SZ og BAS, og undersøgte effekterne af henholdsvis familiær og genetisk (polygen) risiko for SZ og BD på auditoriske reponser samt underliggende kortikale kredsløb, sidstnævnte ved brug af dynamic causal modeling (DCM). Derudover undersøgte vi associationen mellem polygen risiko for psykiske sygdomme og karakterer i matematik og dansk i ungdom og tidlig voksenalder ved brug af data fra landsdækkende, repræsentative kohorter. Som supplement til dette udførte vi en meta-analyse af tidligere undersøgelser af 40 Hz ASSR i patienter med BAS samt et kvalitetsudviklingsprojekt om brugen af neurofysiologisk udredning (elektroencefalografi) i psykiatrien.

Konventionelle analyser af MEG-data viste intakte auditoriske responser hos unge med familiær risiko for SZ eller BAS, hvilket indikerer at de udtalte svækkelser som set i patienter og voksne slægtninge er afhængig af yderligere modning af kortikale kredsløb. DCM-analyserne afslørede dog forandret konnektivitet relateret til både familiær og polygen risiko for SZ og BD, hvilket indikerer at tidlig detektion af sygdomsrelaterede neurofysiologiske forandringer er muligt. Polygen risiko for SZ var associeret med lavere matematik-karakterer, men højere dansk-karakterer, og polygen risiko for BAS var associeret med højere karakterer i begge fag. Dette viser, at genetisk risiko for SZ og BD både kan udtrykkes som styrker og som svagheder. I det kliniske kvalitetsudviklingsprojekt fandt vi begrænset brugbarhed af EEG i psykiatrisk udredning med nuværende metoder. Trods det kliniske potentiale af nye neurofysiologiske biomarkører, kræves der yderligere forskning før en implementering kan finde sted.

Opponenter:

• Marta Garrido, PhD, Professor i psykologi, Melbourne School of Psychological Sciences, The University of Melbourne, Australien.
• Juanita Todd, Professor i psykologi, The University of Newcastle, Australien.
• Charlotte Ulrikka Rask, Klinisk professor, Klinisk professor i Børne- og Ungdomspsykiatri, AUH – Psykiatrien (Forperson for bedømmelsesudvalget)

Vejledere:

• Yury Shtyrov, Professor, CFIN, Aarhus Universitet
• Martin Dietz, Adjunkt, CFIN, Aarhus Universitet
• Ole Mors, Professor, Forskningsenhed for Psykoser, Aarhus Universitetshospital Psykiatrien
• Karl Friston, Professor, Wellcome Centre for Human Neuroimaging, Institute of Neurology, University College London.

Kontakt:

For yderligere information, kontakt venligst

Oskar Hougaard Jefsen
oskar.jefsen@clin.au.dk
+45 30 11 20 66

Download invitation til Oskar Hougaard Jefsens ph.d.-forsvar ...