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Biomedical subjects

Therese van Amelsvoort

Publications and source records attributed to Therese van Amelsvoort.

14 recordsLinked to original sources
PubMed2006

Involvement of hyperprolinemia in cognitive and psychiatric features of the 22q11 deletion syndrome.

Microdeletions of the 22q11 region, responsible for the velo-cardio-facial syndrome (VCFS), are associated with an increased risk for psychosis and mental retardation. Recently, it has been shown in a hyperprolinemic mouse model that an interaction between two genes localized in the hemideleted region, proline dehydrogenase (PRODH) and catechol-o-methyl-transferase (COMT), could be involved in this phenotype. Here, we further characterize in eight children the molecular basis of type I hyperprolinemia (HPI), a recessive disorder resulting from reduced activity of proline dehydrogenase (POX). We show that these patients present with mental retardation, epilepsy and, in some cases, psychiatric features. We next report that, among 92 adult or adolescent VCFS subjects, a subset of patients with severe hyperprolinemia has a phenotype distinguishable from that of other VCFS patients and reminiscent of HPI. Forward stepwise multiple regression analysis selected hyperprolinemia, psychosis and COMT genotype as independent variables influencing IQ in the whole VCFS sample. An inverse correlation between plasma proline level and IQ was found. In addition, as predicted from the mouse model, hyperprolinemic VCFS subjects bearing the Met-COMT low activity allele are at risk for psychosis (OR = 2.8, 95% CI = 1.04-7.4). Finally, from the extensive analysis of the PRODH gene coding sequence variations, it is predicted that POX residual activity in the 0-30% range results into HPI, whereas residual activity in the 30-50% range is associated either with normal plasma proline levels or with mild-to-moderate hyperprolinemia.

Adolescent↗
PubMed2006

The COMT val158met polymorphism and brain morphometry in healthy young adults.

Catechol-O-methyltransferase (COMT) is the most important mechanism for dopamine degradation in the prefrontal cortex and contains a functional polymorphism (val(158)met) influencing enzyme activity. The low-activity met allele has been associated with better performance on cognitive tasks relying on the prefrontal cortex. Whether COMT also affects brain structure, is still unclear. This study investigated the relationship between the COMT val(158)met polymorphism and brain anatomy in healthy young adults. In a cross-sectional study, structural MRI data and DNA for COMT genotyping were obtained from 154 healthy young adults. Statistical Parametric Mapping software (SPM2) and optimized voxel-based morphometry were used to determine total and regional gray and white matter density differences between genotype groups, as well as age-related gray and white matter density differences within the genotype groups. We found a significant effect of COMT genotype on age-related differences in gray and white matter density in females but not in males. In female val carriers increased gray matter in the temporal and parietal lobe and the cerebellum and increased white matter in the frontal lobes were positively correlated with age; in female met homozygotes decreased gray matter density in the parietal lobe and decreased white matter density in the frontal lobes, the parahippocampal gyrus and the corpus callosum were positively correlated with age. These results suggest that the COMT val(158)met polymorphism may affect age-related differences in gray and white matter density in females.

Adolescent↗
PubMed2006

Brain and behaviour in children with 22q11.2 deletion syndrome: a volumetric and voxel-based morphometry MRI study.

In people with velo-cardio-facial syndrome [or 22q11.2 deletion syndrome (22qDS)], a single interstitial deletion of chromosome 22q11.2 causes a wide spectrum of cognitive deficits ranging from global learning difficulties to specific cognitive deficits. People with 22qDS are also at high risk of developing attention-deficit/hyperactivity disorder and autism spectrum disorders in childhood, and schizophrenia in adolescence or adult life. However, the neurobiology of 22qDS, and the relationship between abnormalities in brain anatomy and behaviour, is poorly understood. Thus, we studied the neuroanatomy of 22qDS children using fully automated voxel-based morphometry (VBM) and manually traced single region-of-interest (ROI) analysis. Also, we investigated whether those brain regions that differed significantly between groups were related to behavioural differences within children with 22qDS. We compared the brain morphometry of 39 children and adolescents with 22qDS (mean age: 11 years, SD +/-3, IQ = 67, SD +/-10) and 26 sibling controls (mean age: 11 years, SD +/-3, IQ = 102, SD +/-12). Using VBM, we found, after correction for IQ, that individuals with 22qDS compared with controls had a significant reduction in cerebellar grey matter, and white matter reductions in the frontal lobe, cerebellum and internal capsule. Using single ROI analysis, we found that people with 22qDS had a significant (P < 0.05) reduction in bulk volume bilaterally in the occipital-parietal lobes, but a larger right caudate nucleus and lateral ventricles. Further, within people with 22qDS, there was a significant positive correlation between severity of (i) schizotypy score and grey matter volume of the temporo-occipital regions and the corpus striatum; (ii) emotional problems and grey matter volume of frontostriatal regions; and (iii) social behavioural difficulties and grey matter in frontostriatal regions. Thus, subjects with 22qDS have widespread changes in brain anatomy, particularly affecting white matter, basal ganglia and cerebellum. Also, within 22qDS, regionally specific differences in brain development may partially underpin behavioural differences. We suggest that there is preliminary evidence for specific vulnerability of the frontostriatal and cerebellar-cortical networks in 22qDS.

Adolescent↗
PubMed2006

Processing facial emotions in adults with velo-cardio-facial syndrome: functional magnetic resonance imaging.

We studied the functional neuroanatomy of social behaviour in velo-cardio-facial syndrome (VCFS) using a facial emotional processing task and functional magnetic resonance imaging in adults with this syndrome and controls matched for age and IQ. The VCFS group had less activation in the right insula and frontal brain regions and more activation in occipital regions. Genetically determined abnormalities in pathways including those involved in emotional processing may underlie deficits in social cognition in people with VCFS.

Adult↗
PubMed2005

Occupancy of dopamine D2 receptors by antipsychotic drugs is related to nicotine addiction in young patients with schizophrenia.

RATIONALE: Occupancy of dopamine D2 receptors by antipsychotic drugs depends on the individual availability of D2 receptors and on the dose and type of antipsychotic medication. It has been suggested that a low availability of these receptors may increase the risk for addictive behavior. OBJECTIVE: This study aims to show that patients with relatively high occupancy of D2 receptors by antipsychotic drugs are more prone to nicotine consumption. METHODS: Striatal D2 receptor occupancy by equivalent doses of olanzapine or risperidone was assessed with [123I]iodobenzamide single-photon emission computed tomography (SPECT) in 36 patients with schizophrenia. Smoking status at the time of SPECT imaging was assessed. The number of cigarettes used in the following three consecutive years was estimated with the Life Chart Schedule (LCS). RESULTS: There was a positive and significant relation between D2 receptor occupancy following treatment with olanzapine (n=19) or risperidone (n=12) and the number of cigarettes smoked in three consecutive years (r=0.60, p<0.001) in patients who smoked. There was a significant difference in the percentage of D2 occupancy for smokers (mean 74.3%, SD 12.8, n=31) and nonsmokers (mean 49.8%, SD 9.1, n=5). CONCLUSION: Frequency of cigarette smoking in schizophrenic patients treated with antipsychotic medication is significantly and negatively related to the availability of striatal D2 receptors.

Adult↗
PubMed2005

Obsessive-compulsive symptoms and positive, negative, and depressive symptoms in patients with recent-onset schizophrenic disorders.

OBJECTIVES: To study the relation between obsessive-compulsive symptoms (OCS) and positive, negative, and depressive symptoms in patients with recent-onset schizophrenic disorders. METHODS: We undertook a prospective study of 113 consecutively hospitalized patients with recent-onset schizophrenia or related disorders diagnosed according to DSM-IV criteria. We compared 3 subgroups: one without comorbid OCS, one with OCS not fulfilling DSM-IV criteria for obsessive-compulsive disorder (OCD), and one with comorbid OCD diagnosed according to DSM-IV criteria. We assessed OCS severity at admission and 6 weeks thereafter with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The Positive and Negative Syndrome Scale (PANSS) and the Montgomery-Asberg Depression Rating Scale (MADRS) were independently administered. RESULTS: At admission, patients with schizophrenic disorders and OCD had higher mean MADRS scores than both other groups; patients with OCS not fulfilling DSM-IV criteria for OCD had lower mean PANSS negative subscale scores than both other groups. After 6 weeks, there were no significant between-group differences, and OCS severity remained constant. CONCLUSIONS: Acute patients with recent-onset schizophrenia and OCD have more severe depressive symptoms but do differ in negative symptoms, compared with patients without comorbid OCD. Mild OCS may be related to less severe negative symptoms. During regular inpatient treatment, OCS severity remains constant

Acute Disease↗
PubMed2004

Cognitive deficits associated with schizophrenia in velo-cardio-facial syndrome.

Velo-cardio-facial syndrome (VCFS) is a genetic disorder associated with 22q11 deletion, a characteristic clinical phenotype, behavourial problems, specific cognitive deficits and a high rate of psychosis (particularly schizophrenia). The study of VCFS provides a unique opportunity to identify susceptibility genes for schizophrenia and its associated cognitive deficits. To date, there have been no studies investigating the impact of schizophrenia on cognitive function in adults with VCFS. Therefore we studied the neuropsychological profile of 28 adults with VCFS; 13 with schizophrenia (mean age (+/-S.D.) 34 years +/-11, IQ 71+/-11) and 15 without a history of psychosis (mean age 33 years +/-11, IQ 75+/-11). The VCFS group with schizophrenia compared to the VCFS group without schizophrenia performed significantly (P<0.05) worse on tests of: (1) spatial working memory and strategy formation; (2) the similarities sub-test of the Weschler Adult Intelligence Scale (WAIS); (3) visual recognition; (4) and attention. These deficits may reflect differences in the development and function of frontal brain regions, and this might increase the risk of developing schizophrenia in VCFS. Future studies will need to address how haploinsufficiency of genes on chromosome 22q11 might affect cognition and its relation to the development of psychosis.

Adult↗
PubMed2004

Brain anatomy in adults with velocardiofacial syndrome with and without schizophrenia: preliminary results of a structural magnetic resonance imaging study.

CONTEXT: Velocardiofacial syndrome is associated with interstitial deletions of chromosome 22q11, mild to borderline learning disability, characteristic dysmorphology, and a high prevalence of schizophrenia. The biological basis for this increased risk for schizophrenia is unknown, but people with velocardiofacial syndrome may have genetically determined differences in brain anatomy that predispose to the development of schizophrenia. OBJECTIVE: To determine whether there are differences in brain structure between subjects with velocardiofacial syndrome with and without schizophrenia. DESIGN: A cross-sectional quantitative structural magnetic resonance imaging study in 39 adult subjects. SETTING: Referrals were made through medical genetics clinics and psychiatric services throughout the United Kingdom. PARTICIPANTS: Thirteen subjects with velocardiofacial syndrome and schizophrenia, 12 with velocardiofacial syndrome without history of a psychosis, and 14 healthy controls volunteered to participate after screening for eligibility. MAIN OUTCOME MEASURES: Total and regional brain volumes were analyzed by means of manual tracing, and gray- and white-matter densities were obtained by computerized voxel-based methods. RESULTS: People with velocardiofacial syndrome and schizophrenia, compared with both controls and nonschizophrenic patients with velocardiofacial syndrome, had a significant (P<.05) reduction in volume of whole-brain (white + gray) matter and whole-brain white matter, and an increase in total and sulcal cerebrospinal fluid volume. Both velocardiofacial syndrome groups had a reduced cerebellar volume compared with controls. CONCLUSIONS: Within velocardiofacial syndrome, schizophrenia is associated with generalized differences in brain anatomy, but white matter may be particularly implicated. Studies with larger samples are needed to replicate our findings.

Adult↗
PubMed2004

Subjective experience and dopamine D2 receptor occupancy in patients treated with antipsychotics: clinical implications.

OBJECTIVES: This paper gives an overview of studies on the association between dopaminergic neurotransmission and the subjective experience of patients with schizophrenia. METHODS: We undertook a review of the literature. RESULTS: Dopaminergic neurotransmission may be relevant for subjective experience. Higher striatal D2 receptor occupancy by typical and atypical antipsychotics is related to worse subjective experience, more severe negative symptoms, and depression. Individuals with lower baseline dopamine function are at an increased risk for dysphoric responses during antipsychotic therapy with dopaminergic-blocking drugs. There is preliminary evidence that a window of striatal D2 receptor occupancy between 60% and 70% is optimal for the subjective experience of patients. These occupancies are often reached even with low dosages of antipsychotic drugs. CONCLUSIONS: Reaching an optimal dopamine D2 receptor occupancy is clinically relevant, since subjective experience associated with antipsychotic medication is related to medication compliance. Antipsychotic drug dosages often need to be lower than levels in common use.

Antipsychotic Agents↗
PubMed2002

Mood, cognition and Alzheimer's disease.

There is good evidence for sex differences in brain disease, and that oestrogen modulates brain development and ageing. For example, females are significantly more likely to suffer from Alzheimer's disease, depression and late-onset psychosis than are men. Moreover, hormone replacement therapy may reduce the rate of cognitive decline in post-menopausal women and reduce their risk of developing Alzheimer's disease (as compared to post-menopausal women who do not take hormone replacement therapy). The neurobiological basis of these differences in brain disease and ageing was unknown until relatively recently. In this chapter we discuss results of studies demonstrating that sex steroids (i) are crucial for development and ageing of brain regions affected in Alzheimer's disease; (ii) interact with neuronal networks and chemical systems at many different levels in brain, and (iii) affect mood and cognitive function in elderly women without Alzheimer's disease. The current literature supports the hypothesis that sex steroids can modulate brain ageing and provides a number of potential neurobiological explanations for the cognitive effects of hormone replacement therapy. There is only limited evidence that hormone replacement therapy is effective in women already suffering from Alzheimer's disease. Nonetheless, recent work may lead to new prevention strategies for age-related cognitive decline and brain diseases such as Alzheimer's disease.

Aged↗
PubMed2002

Brain anatomy and sensorimotor gating in Asperger's syndrome.

Asperger's syndrome (an autistic disorder) is characterized by stereotyped and obsessional behaviours, and pervasive abnormalities in socio-emotional and communicative behaviour. These symptoms lead to social exclusion and a significant healthcare burden; however, their neurobiological basis is poorly understood. There are few studies on brain anatomy of Asperger's syndrome, and no focal anatomical abnormality has been reliably reported from brain imaging studies of autism, although there is increasing evidence for differences in limbic circuits. These brain regions are important in sensorimotor gating, and impaired 'gating' may partly explain the failure of people with autistic disorders to inhibit repetitive thoughts and actions. Thus, we compared brain anatomy and sensorimotor gating in healthy people with Asperger's syndrome and controls. We included 21 adults with Asperger's syndrome and 24 controls. All had normal IQ and were aged 18-49 years. We studied brain anatomy using quantitative MRI, and sensorimotor gating using prepulse inhibition of startle in a subset of 12 individuals with Asperger's syndrome and 14 controls. We found significant age-related differences in volume of cerebral hemispheres and caudate nuclei (controls, but not people with Asperger's syndrome, had age-related reductions in volume). Also, people with Asperger's syndrome had significantly less grey matter in fronto-striatal and cerebellar regions than controls, and widespread differences in white matter. Moreover, sensorimotor gating was significantly impaired in Asperger's syndrome. People with Asperger's syndrome most likely have generalized alterations in brain development, but this is associated with significant differences from controls in the anatomy and function of specific brain regions implicated in behaviours characterizing the disorder. We hypothesize that Asperger's syndrome is associated with abnormalities in fronto-striatal pathways resulting in defective sensorimotor gating, and consequently characteristic difficulties inhibiting repetitive thoughts, speech and actions.

Adolescent↗