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Microglia activation in recent-onset schizophrenia: a quantitative (R)-[11C]PK11195 positron emission tomography
Bart N van Berckel1, Matthijs G Bossong, Ronald Boellaard
1Department of Psychiatry, Rudolf Magnus Institute for Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands. B.Berckel@VUmc.nl
Background:
Schizophrenia is a brain disease involving progressive loss of gray matter of unknown cause. Most likely, this loss reflects neuronal damage, which should, in turn, be accompanied by microglia activation. Microglia activation can be quantified in vivo using (R)-[(11)C]PK11195 and positron emission tomography (PET). The purpose of this study was to investigate whether microglia activation occurs in patients with recent-onset schizophrenia.
Methods:
Ten patients with recent-onset schizophrenia and 10 age-matched healthy control subjects were included. A fully quantitative (R)-[(11)C]PK11195 PET scan was performed on all subjects, including arterial sampling to generate a metabolite-corrected input curve.
Results:
Compared with control subjects, binding potential of (R)-[(11)C]PK11195 in total gray matter was increased in patients with schizophrenia. There were no differences in other PET parameters.
Conclusions:
Activated microglia are present in schizophrenia patients within the first 5 years of disease onset. This suggests that, in this period, neuronal injury is present and that neuronal damage may be involved in the loss of gray matter associated with this disease. Microglia may form a novel target for neuroprotective therapies in schizophrenia.
Insights
Microglia activation, a marker of brain injury, is present in recent-onset schizophrenia patients. This finding suggests neuronal damage contributes to gray matter loss and may offer a new therapeutic target.
Area of Science:
- Neuroscience
- Psychiatry
- Medical Imaging
Background:
- Schizophrenia is a progressive brain disease characterized by gray matter loss of unknown etiology.
- Neuronal damage is hypothesized to underlie gray matter loss, with microglia activation as a potential indicator.
- Microglia activation can be quantified non-invasively using (R)-[(11)C]PK11195 positron emission tomography (PET).
Purpose of the Study:
- To investigate the presence and extent of microglia activation in patients diagnosed with recent-onset schizophrenia.
Main Methods:
- A cohort of 10 patients with recent-onset schizophrenia and 10 age-matched healthy controls underwent quantitative (R)-[(11)C]PK11195 PET scans.
- Arterial blood sampling was performed to generate metabolite-corrected input curves for accurate quantification.
Main Results:
- Patients with schizophrenia exhibited significantly increased binding potential of (R)-[(11)C]PK11195 in total gray matter compared to healthy controls.
- No significant differences in other measured PET parameters were observed between the groups.
Conclusions:
- Activated microglia are detectable in the brains of schizophrenia patients within the initial 5 years of disease onset.
- The presence of activated microglia suggests ongoing neuronal injury during this early disease phase, potentially contributing to gray matter reduction.
- Microglia represent a promising novel target for developing neuroprotective strategies in schizophrenia treatment.
