Our research group is currently working on three main projects:
I. The genetic architecture of human brainstem structures and their involvement in neurological and psychiatric disorders
The brainstem is an essential regulator of vital bodily functions and is implicated in the pathophysiology of common brain disorders. However, the structure and genetic architecture of the brainstem regions remain understudied. Using magnetic resonance imaging, we examine volumes of brainstem structures, including the mesencephalon, pons, and medulla oblongata in healthy individuals and participants with neurological or psychiatric disorders. We conduct genome wide association studies of brainstem volumes in healthy individuals and assess the polygenic overlap with brainstem-related disorders. We also examine volumes of brainstem structures in individuals with neurological and psychiatric disorders and compare these to volumes of healthy individuals.
II. Sleep-wake-dependent brain plasticity in health and depression
Sleep insufficiency is prevalent, impairs human functioning, and causes vast negative health effects and societal costs. Sleep disturbances are also common in individuals with neurological and psychiatric disorders. In addition, one night of sleep deprivation has robust antidepressant effects in major depressive disorder (MDD), yet the majority of sleep deprivation-responders relapse after recovery sleep. We and others have recently found evidence for structural and functional brain changes after hours of wake and sleep using magnetic resonance imaging (MRI), including alterations in cerebral cortical thickness, white matter microstructure, cerebral blood flow, and functional brain connectivity. Together, the results raise the prospect of sleep-wake-dependent human brain plasticity. However, the relationship between these plasticity processes and antidepressant response to sleep deprivation in MDD remains unknown. The overall goals of this project are A) to clarify whether structural and functional brain plasticity are characteristics of the human sleep-wake cycle and B) to reveal neurobiological mechanisms underlying the acute antidepressant effects of sleep deprivation and relapse of depressive symptoms after recovery sleep in MDD. We will examine 100 healthy controls and 50 individuals with MDD using structural and functional MRI techniques before, during, and after one night of sleep deprivation and recovery sleep. By combining in vivo brain imaging with characterization of sleep and psychiatric phenomenology, this research project has the potential to provide new knowledge about sleep and wake in health and depression.
III. Genes, computational modelling, and in vivoelectrophysiology in severe mental illnesses: from pathophysiology towards personalized medicine
The clarification of central pathophysiological mechanisms, identification of patient subgroups with distinct neural abnormalities, and development of novel diagnostic tools are critical steps towards personalized medicine and improved outcomes in schizophrenia (SCZ) and bipolar disorder (BD). On the basis of preclinical research and landmark genome-wide association studies, impaired glutamatergic neurotransmission and dysregulated neuronal excitability have emerged as two of the leading candidate mechanisms in SCZ and BD. The present project is conducted at the Norwegian Centre for Mental Disorders Research (NORMENT), where glutamatergic neurotransmission and neuronal excitability will be examined across genetics, induced pluripotent stem cell (iPSC)-derived neurons, and in vivo electrophysiology in healthy individuals and individuals with SCZ or BD. This multi-disciplinary approach has the potential to provide new knowledge about central disease mechanisms in SCZ and BD.