Biomedical subjects

Machteld Marcelis

Publications and source records attributed to Machteld Marcelis.

4 recordsLinked to original sources

PubMed2006

Evidence that brain tissue volumes are associated with HVA reactivity to metabolic stress in schizophrenia.

BACKGROUND: Although liability to psychosis is thought to have its origins in cerebral alterations, expressed as cerebral grey and white matter loss, less is known about the degree to which such vulnerabilities impact on functional parameters, in particular altered stress reactivity. Breier et al. [Breier, A., Davis, O.R., Buchanan, R.W., Moricle, L.A., Munson, R.C., 1993b. Effects of metabolic perturbation on plasma homovanillic acid in schizophrenia. Relationship to prefrontal cortex volume. Arch. Gen. Psychiatry 50(7), 541-550] reported that lower prefrontal cortex volume was associated with altered metabolic stress response, but this finding has never been replicated. METHODS: Thirty-one patients with psychosis underwent structural magnetic resonance imaging scanning and a metabolic stress paradigm (glucoprivic 2-deoxyglucose (2DG) condition versus placebo condition) that yielded information on plasma homovanillic acid (HVA) reactivity. Total cerebral tissue volumes were derived from automated segmentation procedures. Associations between metabolic stress and tissue volumes (as well as their interactions) on the one hand, and plasma HVA level on the other, were investigated using multilevel random regression techniques. RESULTS: Analysis revealed a significant increase in plasma HVA over time in the 2DG condition. The increase in HVA in the stress condition was stronger in patients with lower grey and white matter volumes. There was no significant interaction between metabolic stress and CSF volume. CONCLUSION: Lower grey and white matter volumes in schizophrenia are associated with a dysregulated dopaminergic/noradrenergic mediated stress response. These findings may support the hypothesis that alterations in cortico-subcortical connections affect psychosis susceptibility through an altered stress response.

Adolescent↗

PubMed2005

Subtle fluctuations in psychotic phenomena as functional states of abnormal dopamine reactivity in individuals at risk.

BACKGROUND: Subjects at increased risk for psychosis experience continuous variation in the intensity of subtle psychotic experiences in response to minor stressors. It was investigated whether this psychotic reactivity in individuals at risk for psychosis is the exophenotypic expression of an underlying endophenotype characterized by a hyperreactive dopamine (DA) system. METHODS: First-degree relatives (n = 47) and control subjects (n = 49) were studied with the Experience Sampling Method (ESM), a structured diary technique assessing current context and psychopathology in daily life, to assess psychotic experiences in response to stress. A metabolic perturbation paradigm (administration of 2-deoxy-D-glucose inducing a mild state of glucoprivation) causing plasma elevation of homovanillic acid (HVA) was used as a proxy of DA reactivity. RESULTS: Multilevel regression analyses revealed that the interaction between HVA reactivity and daily stress in their effect on psychotic experiences differed according to underlying vulnerability. In the first-degree relatives, underlying HVA reactivity modified the psychotic experiences to daily stress, whereas no such effect was found in control subjects. CONCLUSIONS: These results suggest that psychotic experiences in response to minor stresses in the flow of daily life may be functional states of an underlying abnormal DA reactivity in subjects at risk to develop psychosis. The results add credence to the suggestion that abnormal DA reactivity may be part of the substrate that increases risk for psychotic symptoms in individuals at risk.

Adult↗

PubMed2003

Searching for a structural endophenotype in psychosis using computational morphometry.

Structural cerebral abnormalities are frequently observed in schizophrenia. These abnormalities may indicate vulnerability for the disorder, as evidenced by reports of familial clustering of measures identified through region-of-interest analyses using manual outlining procedures. We used computational morphometry to detect structural differences within the entire brain to further examine possible structural endophenotypes. Magnetic resonance imaging scans were obtained in 31 psychotic patients, 32 non-psychotic first-degree relatives of psychotic patients and 27 healthy controls. The images were processed using an automated procedure, yielding global grey matter, white matter, CSF and total brain volume. The relative distribution of grey matter was compared between groups on a clustered-voxel basis. Global grey matter and total brain volume did not differ between the groups. White matter volume was significantly higher and CSF volume significantly lower in relatives compared to both cases and controls. The clustered-voxel based group comparison yielded evidence for significant grey matter deficits in fronto-thalamic-cerebellar regions, in psychotic patients, whereas the most prominent deficits in relatives involved the cerebellum. Patients with psychosis and first-degree healthy relatives of patients with psychosis show cerebellar abnormalities, which may constitute a marker of genetic transmission.

Adolescent↗

PubMedDate not supplied

Nonreplication of the association between ab-ridge count and cerebral structural measures in schizophrenia.

The origins of cerebral abnormalities in psychotic patients remain unknown. Dermatoglyphics are suitable markers of prenatal injury due to their fetal ontogenesis and their susceptibility to some of the factors that also affect cerebral development. In a previous study, positive associations between brain volumetric measures and a dermatoglyphic marker, the ab-ridge count, were reported. The present study is an attempt to replicate that finding in an independent sample. Magnetic resonance imaging (MRI) scans and dermatoglyphic measures were available for 29 schizophrenia patients (Research Diagnostic Criteria [RDC] criteria) and 26 unrelated healthy controls. The images were processed using an automated procedure, yielding volumes of total grey matter, white matter, cerebrospinal fluid (CSF), and total brain volume. The ab-ridge count was not positively associated with brain volumes in either patients or controls. The present findings do not support the hypothesis that the changes in brain volume seen in patients with schizophrenia are of prenatal origin.

Adolescent↗