Patients are included in this study in connection with their first psychotic episode and before they had received any antipsychotic medication. A control group of age- and gender-matched healthy controls were also included.
Our aim is to stratify patients based on their neurochemical (dopamine, glutamate, and GABA) and linked functional- (CBF and fMRI), connective- (fMRI, DTI), structural- (MRI), cognitive-, and EEG- disturbances – and to evaluate the prognostic value of these in terms of treatment outcome and progressive loss of brain tissue and functions.
Data will contribute with a coherent understanding of the disturbed mechanisms in key brain networks believed to be involved in the pathophysiology of schizophrenia during the first two years after the patients' first antipsychotic treatment. The study involves a standardized intervention contributing with knowledge on the significance of normalization or partial normalization of the disturbances on outcome.
Patients are treated with the partial dopamine D2 agonist aripiprazole (tool compound) after completing baseline investigations Aripiprazole is a first-line antipsychotic compound with a favourable (mild) side-effect profile for treatment of patients who have never previously received antipsychotic medication. Animal research has shown that aripiprazole might modify both presynaptic dopaminergic glutamatergic and GABAergic brain activity (Yang & Wang, 2008; Koprivica et al. 2011; Abekawa et al. 2011).
Levels of glutamate and GABA are measured by 1H-MRS in the anterior cingulate cortex and thalamus. Striatal dopamine synthesis capacity is measured with F-DOPA PET. The influence of glutamate, GABA, and dopamine activity for treatment outcome before and after the intervention is investigated. Additional modalities include assessment of pseudo-continuous arterial spin labeling (pCASL), i.e. CBF, blood-oxygenation level-dependent (BOLD), and resting state fMRI by whole brain MRI scanning. As in the other first-episode cohorts and to allow for cross cohort analyses, structural brain changes (in addition to DTI) with MRI, cognitive functions with a neuropsychological battery, reward processing with fMRI, early information processing with event related EEG and EMG (psychophysiological examinations) are also assessed for cohort E.
PhD theses based on data from this project:
- Kirsten B. Bojesen "Improving treatment of patients with schizophrenia – glutamergic disturbances as a possible marker of choice-of-treatment" (expected 2017)
- Kasper Jessen " A longitudinal study of cortical thickness and surface in antipsychotic-naïve first-episode schizophrenia patients: The impact of neurochemical disturbances and cognitive deficits" (expected 2017)
- Marie Bjerregaard Jensen "Associations between earlier and later matured cognitive functions and structural connectivity in antipsychotic-naïve first-episode schizophrenia" (expected 2018)
- Anne Mette Sigvard "The predictive value of different neurochemical profiles for treatment outcome in antipsychotic-naïve schizophrenia patients" (expected 2019)
- Karen Tangmose "Dopamine synthesis capacity and reward processing in first-episode psychosis" (expected 2020)