Kirsten Borup Bojesen, MD, PhD
Residency trainee in psychiatry, postdoctoral researcher
Copenhagen University Hospital, Center for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Center Glostrup, Nordstjernevej 41, 2600 Glostrup
As a clinician-scientist, I have been struck by the large proportion of patients with schizophrenia insufficiently treated with antipsychotics and by the negative impact of cognitive deficits on everyday life. This has inspired me to explore the neurotransmitter aberrations underlying insufficient treatment response and cognitive deficits in patients with psychosis with a key focus on glutamate and GABA. My hope is that research on the impact of glutamatergic and GABAergic neurotransmitter disturbances on insufficient treatment outcome and cognition can pave the way for development of novel therapeutics.
My research has focused on glutamatergic and GABAergic aberrations in initially antipsychotic-naïve patients with first-episode psychosis and the impact of these disturbances on short- and long-term treatment outcome as well as cognitive performance. Specifically, we have found that higher levels of glutamate in thalamus and lower levels of GABA in dorsal Anterior Cingulate Cortex (dACC) are present from illness onset in antipsychotic-naïve first-episode patients and related to poor short-term treatment outcome after 6 and 26 weeks. Moreover, low GABA levels in dACC at illness onset are associated with poor functional outcome after two years of illness, and lower levels of glutamate in the dACC are associated with impaired cognitive function. Going further into the neurobiological underpinnings of insufficient treatment response, we investigated if brain glutamate and GABA levels were related to striatal dopaminergic function that is the main target of antipsychotic compounds. We observed that lower GABA levels in dACC were associated with higher striatal perfusion during the first two years of illness, suggesting that prefrontal GABA levels have a downregulatory effect on striatal activity and may be a novel treatment target. Furthermore, an aberrant interrelation between dACC levels of GABA and dopamine synthesis capacity in nucleus accumbens assessed with positron emission tomography could identify antipsychotic-naïve patients from healthy controls, whereas individual neurotransmitters were unable to do so, suggesting that aberrant interactions between neurotransmitters are more crucial for development of schizophrenia than single neurotransmitter disturbances. Currently, we examine the trajectory of glutamate levels in dACC and thalamus during the first two years of illness and relate neurotransmitter levels to long-term treatment outcome and cognitive function. Moreover, we investigate if a glutamatergic compound developed for neurological disorders is effective in patients with first-episode psychosis.
Our findings so far imply that treatment targeting glutamatergic and GABAergic disturbances can be beneficial in first-episode patients during the first two years of illness. As novel treatments are warranted not only during first-episode psychosis but also in the more chronic stage of the illness, we are currently preparing to re-examine brain levels of glutamate and GABA in the same cohort of patients and healthy controls after ten years.
I am always thrilled to attend the SIRS conference and get inspirated by both junior and senior researchers dedicating their time to improve the treatment and everyday life for patients with schizophrenia and psychotic disorders. The SIRS early career award 2023 and mentor program was very helpful in expanding my international network, and I especially gained from guidance on funding, publishing strategies, and life-work balance in academia. The program has supported me in developing my research career trajectory. It makes me believe that our combined international effort into unravelling the neurobiological and environmental factors underlying schizophrenia will lead to development of novel treatment options during the next decades.
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