E. Caspers

Microglia Activation in Recent-Onset Schizophrenia: A Quantitative (R)-[11C]PK11195 Positron Emission Tomography Study

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.

Excessive Brain Volume Loss Over Time in Cannabis-Using First-Episode Schizophrenia Patients

OBJECTIVE Cerebral gray matter volume reductions have been found to progress over time in schizophrenia, with larger decreases related to poorer outcome, which has also been associated with cannabis use in schizophrenia patients. Progressive gray matter changes in patients who use cannabis may be more extensive than in those who do not. METHOD Patients with recent-onset schizophrenia (N=51) and matched healthy subjects (N=31) were included. For all subjects, magnetic resonance imaging scans were obtained at inclusion (T0) and at 5-year follow-up (T5). Nineteen patients used cannabis but no other illicit drugs; 32 patients did not use any drugs during the 5-year follow-up. At T5, clinical outcome was measured. Cumulative amount of antipsychotic medication during the interval was calculated. At T0 and T5, total brain, gray and white matter, and lateral and third ventricle volumes were measured. Univariate analysis of covariance and pairwise comparisons were performed. RESULT Schizophrenia patients showed a larger gray matter volume decrease over time than healthy subjects. They also showed larger increases in lateral and third ventricle volumes than healthy subjects and patients who did not use cannabis during follow-up. This decrement was significantly more pronounced in the patients who continued to use cannabis. These differences could not be attributed to outcome or baseline characteristics. CONCLUSIONS First-episode schizophrenia patients who use cannabis show a more pronounced brain volume reduction over a 5-year follow-up than patients with schizophrenia who do not use cannabis. These results may help explain some of the detrimental effects of cannabis use in schizophrenia.

Psychosis and brain volume changes during the first five years of schizophrenia

The underlying mechanisms explaining brain volume changes in schizophrenia are not yet understood, but psychosis might be related to these changes. Forty-eight patients with first-episode schizophrenia underwent Magnetic Resonance Imaging brain scanning at inclusion and after five years. An association was found between longer duration of psychosis, larger gray matter volume decrease and larger ventricular volume increase. These findings strongly suggest that psychosis contributes to brain volume reductions found in schizophrenia.

Brain volumes as predictor of outcome in recent-onset schizophrenia: a multi-center MRI study

Gray matter brain volume decreases have been found in patients with schizophrenia as compared to healthy control subjects measured by using Magnetic Resonance Imaging (MRI). An association has been suggested between decreased gray matter volume and poor outcome in chronically ill patients with schizophrenia. The present longitudinal multi-center study investigated whether gray matter volume at illness onset can predict poor outcome in recent-onset schizophrenia after a follow-up of approximately 2 years. An MRI calibration study was performed since scans of patients with recent-onset psychosis were conducted at three sites with 1.5 T MR scanners from two different manufacturers. Applying a linear scaling procedure on the histogram improved comparability between volume measurements acquired from images from the different scanners. Brain scans were obtained from 109 patients with recent-onset schizophrenia. Volumes of intracranium, total brain, cerebral gray and white matter, third and lateral ventricles, and cerebellum were measured. After a mean follow-up period of approximately 2 years, measurements of symptoms, functioning, need for care, and illness history variables were assessed. No significant correlations were found between the brain volume measures and any of these measures. Gray matter volume at illness onset does not predict outcome after 2 years in recent-onset schizophrenia.

Smooth pursuit eye movement (SPEM) in patients with multiple complex developmental disorder (MCDD), a subtype of the pervasive developmental disorder

Objective. Multiple complex developmental disorder (MCDD) is a well-defined and validated behavioural subtype of pervasive developmental disorder-not otherwise specified (PDD-NOS) and is thought to be associated with a higher risk of developing a schizophrenic spectrum disorder. The question was addressed whether patients with MCDD show the same psychophysiological abnormalities as seen in patients with schizophrenia. Method. Smooth pursuit eye movement (pursuit gain and saccadic parameters) was measured in children with either MCDD (n=18) or autism (n=18), and in age- and IQ-matched controls (n=36), as well as in a group of adult patients with schizophrenia (n=14) and a group of adult controls (n=17). Results. We found the expected effect of lower velocity gain and increased number of saccades in schizophrenic patients. Children with MCDD also showed a lower velocity gain compared to controls children. In contrast, velocity gain was similar in autistic subjects and controls. No differences for velocity gain were found in a direct comparison between MCDD and autism. Saccadic parameters were not significantly different from controls in either MCDD or autistic subjects. Conclusion. Children with MCDD, like schizophrenic adults, show a reduced velocity gain, which could indicate that schizophrenia spectrum disorders and MCDD share (at least to some degree) a common neurobiological background.