Genetic risk variants for schizophrenia and bipolar disorder
NORMENT has been involved in discoveries of new gene variants associated with severe mental illness. These include large international studies reporting over 100 genetic variants related to schizophrenia (PGC SCZ 2014, Trubetskoy 2022) and more than 60 risk variants associated with bipolar disorder (Stahl 2019, Mullins 2021). Risk genes are related to brain development, neuronal signaling, and the immune system. Many of the genetic variants are shared between schizo- phrenia and bipolar disorder. NORMENT researchers have also developed novel statistical tools that boost the discovery of genetic variants and improve prediction in mental illness (Frei 2019, van der Meer 2020).
Genetic overlap between mental disorders, personal traits, and other disorders
We have found that genetic variants involved in schizophrenia or bipolar disorder overlap with other mental disorders (PGC 2019, Hindley 2022) and with brain disorders such as ADHD (O’Connell 2021). Further, we have discovered shared genes for mental disorders and personal traits, including cognitive function (Smeland 2017), intelligence (Smeland 2019), personality (Hindley 2022), body mass index (Bahrami 2020), cardiovascular risk factors (Rødevand 2023), and cannabis use (Cheng, Parker 2023).
Brain structure and networks in mental illness, and relation to genes and environment
By using advanced brain imaging technology, NORMENT has contributed with new knowledge about how the brain is affected in mental illness. We have demonstrated cortical brain abnormalities in bipolar disorder (Hibar 2018), reductions (Haukvik 2015) and sex differences (Barth 2023) in hippocampal subfield volumes in schizophrenia, and white matter microstructure alterations in adolescent psychosis (Barth 2023). We have reported that schizophrenia is associated with increased interindividual differences in brain structure (Alnæs 2019) and that cerebellum is among the most affected brain regions in this disorder (Moberget 2018).
Researchers at NORMENT have also identified genetic variants linked to specific brain regions in mental illness, including the brain stem (Elvsåshagen, Bahrami 2020), thalamus (Elvsåshagen 2021), hippocampus (van der Meer 2020), and cor- tical brain areas (Cheng 2021). We have demonstrated that brain structural measures in mental disorders are associated with factors such as obstetric complications (Wortinger 2022) and use of antipsychotic medication (Jørgensen 2016).
Our research has also shown that alterations of specific nerve fibers in the brain of children and adolescents may increase the risk of mental illness later in life (Alnæs 2018). We have discovered a fingerprint-like pattern in the brain that evolves during development and is associated with mental health challenges (Kaufmann 2017), and we have reported distinct patterns of brain aging in schizophrenia and other disorders (Kaufmann 2019).
The role of the immune system in mental disorders
NORMENT has gained new knowledge about how the immune system is involved in mental illness, both on a genetic level, and in relation to clinical and cognitive symptoms. We have demonstrated abnormalities in a neuroprotective immune pathway in schizophrenia and bipolar disorder (Engh 2022) and dysfunctions of biological pathways associated with the immune system in both disorders (Steen 2020, Torsvik 2023).
Increased immune activity in mental illness has been linked to cognitive impairment (Sæther 2022, Fathian 2018), illness course severity (Elkjær Greenwood Ormerod 2022, Hoprekstad 2023), and childhood trauma (Aas 2017). We have worked to identify new drug treatment targeted at the immune system (Kroken 2019, Nasib 2020) and reported that different antipsychotic drugs impact immune levels differently (Fathian 2022).
Factors that influence course and outcome of mental illness
NORMENT has identified several environmental, clinical, and genetic factors that are important for clinical outcome and prediction of illness course in mental disorders. We have shown that illness outcome is affected by environmental factors such as early trauma (Aas 2014, Vaskinn 2021, Ottesen 2023), obstetric complications (Wortinger 2020), migration (Berg 2015), and substance use, including tobacco smoking (Icick 2019) and cannabis use (Lagerberg 2014, Helle 2016, Ringen 2016).
Our research has shown that immune markers (as described above), serum lipids (Gjerde 2018), polygenic scores (Engen 2020, Werner 2020), and sleep disturbances (Laskemoen 2021) influence the course of mental illness. Further, we have identified causes and predictors of premature death in first-episode schizophrenia spectrum disorders (Melle 2017).
We have also demonstrated that cognitive deficits in mental disorders do not worsen over time, by showing that cognitive functions in first-episode schizophrenia and bipolar disorder are stable after over 1 year (Haatveit 2015, Demmo 2017) and improve over 10 years (Flaaten 2023).
Medication effects and stem cells
NORMENT has documented significant differences in effectiveness of antipsychotic medication (Johnsen 2020) and sex differences in effects and adverse effects of antipsychotic medication (Hoekstra 2021). We have identified genetic factors that are important for drug treatment response (Athanasiu 2015, Akkouh 2020, Akkouh 2022), and our research on anti-inflammatory drugs has provided promising results for treatment alternatives (Kroken 2019, Nasib 2020).
The long-term Centre funding have also allowed us to develop an advanced stem cells technology lab. We have used this methodology to better understand disease mechanisms in mental disorders, develop better medication, and to study the effect of pharmacological treatment such as Lithium (Osete 2021) and clozapine (Akkouh 2022).