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Biomedical subjects

Don Linszen

Publications and source records attributed to Don Linszen.

16 recordsLinked to original sources
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↗
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

The environment and schizophrenia: the role of cannabis use.

Cannabis use is associated with poor outcome in existing schizophrenia and may precipitate psychosis in individuals with preexisting liability. To investigate the overall effect size and consistency of the association between cannabis and psychosis, a meta-analysis from prospective studies was carried out. The pooled odds ratio was 2.1 (95% CI: 1.7-2.5) and could not be explained by confounding or reverse causality. Evidence suggests that cannabis is a component cause in the development and prognosis of psychosis, in which mechanisms of gene-environment interaction are most likely to explain this association. Potential new methods to directly link genetic liability to the effects of cannabis are discussed.

Genetic Predisposition to Disease↗
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↗
PubMed2005

The European Prediction of Psychosis Study (EPOS): integrating early recognition and intervention in Europe.

This paper provides the rationale and design of the European Prediction of Psychosis Study (EPOS), the first European prospective transnational field study of the prodrome and moderating risk/resilience factors of psychosis. As different health systems provide different structures of care, prevention programmes will only be successfully implemented and sustained system-wide, if they can be adapted to the system's special opportunities and needs. EPOS will provide a sound data base for a future evidence-based prevention of psychosis. Data on the recruitment of subjects and on the distribution of the four clinical criteria for an at-risk mental state for psychosis are given.

Journal Article↗
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

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↗
PubMed2003

Subjective experience and D2 receptor occupancy in patients with recent-onset schizophrenia treated with low-dose olanzapine or haloperidol: a randomized, double-blind study.

OBJECTIVE: The authors tested the hypothesis that a dopamine D(2) receptor occupancy level between 60% and 70% in patients with recent-onset schizophrenia would result in optimal subjective experience. In addition, they sought preliminary evidence on whether subjective experience is better with low-dose olanzapine than with low-dose haloperidol. METHOD: Subjects (N=24) who met DSM-IV criteria for schizophrenia were randomly assigned to 6 weeks of double-blind treatment with either olanzapine, 7.5 mg/day, or haloperidol, 2.5 mg/day. Subjective experience, psychopathology, and extrapyramidal symptoms were assessed at baseline and at endpoint. After 6 weeks, D(2) receptor occupancy was assessed with [(123)I]iodobenzamide single photon emission computed tomography. RESULTS: The two study groups were similar at baseline. After 6 weeks, patients receiving olanzapine had a significantly lower mean dopamine D(2) receptor occupancy (51.0%, range=36%-67%) than those given haloperidol (65.5%, range=45%-75%). Receptor occupancy between 60% and 70% was associated with optimal subjective experience, and subjective experience improved significantly in the haloperidol group. CONCLUSIONS: A level of D(2) receptor occupancy between 60% and 70% is optimal for subjective experience of patients with recent-onset schizophrenia. Substantial interindividual variation in D(2) receptor occupancy was seen at fixed low-dose levels of olanzapine and haloperidol. Olanzapine, 7.5 mg/day, showed no superior subjective response over haloperidol, 2.5 mg/day. Olanzapine may need to be dosed higher than 7.5 mg/day for most patients with recent-onset schizophrenia, and haloperidol needs to be individually titrated in the very low dose range to reach optimal occupancy.

Adolescent↗
PubMed2002

Attitudes of patients toward the first psychotic episode and the start of treatment.

Consecutively admitted patients with recent-onset schizophrenia disorders (n = 56) were interviewed about their awareness of mental disorder at first occurrence of psychotic symptoms, their views about the necessity of psychiatric treatment, their perception of the role of others in initiating psychiatric treatment, and suggestions they might have about getting treatment started at an earlier point in time. About 57 percent of the patients had at least some awareness of having a mental disorder at onset of psychotic symptoms, and 61 percent of the sample believed psychiatric help was unnecessary prior to the start of psychiatric treatment. A majority of the patients (91%) perceived others to be essential in initiating treatment. Most patients (82%) thought that no change is needed on the part of professional caregivers in order to facilitate early treatment. Some awareness of mental disorder at onset was related to a shorter duration of untreated psychosis (DUP). Delaying treatment until patients themselves become aware of the need for treatment may enlarge DUP.

Adolescent↗
PubMed2002

The trainee project: family-aided vocational rehabilitation of young people with schizophrenia.

This study explored the initial results of a family-aided vocational rehabilitation program for young people with schizophrenia in The Netherlands. Their parents act as 'job-finders" and traineeship providers. The traineeships obtained for the participants reflect their interests and capabilities, and the participants reported an increase in self-esteem. Some trainees entered paid employment within one year. The results suggest that family involvement, if it is tailored to individual possibilities and combined with key elements of the Individual Placement and Support model, can make a useful contribution to the vocational rehabilitation of young people with schizophrenia.

Adult↗
PubMed2002

Obsessive-compulsive symptoms during treatment with olanzapine and risperidone: a prospective study of 113 patients with recent-onset schizophrenia or related disorders.

OBJECTIVE: To determine whether severity of obsessive-compulsive symptoms (OCS) differs during treatment with olanzapine or risperidone and to establish whether duration of antipsychotic treatment is related to severity of OCS. METHOD: We conducted a prospective study of consecutively hospitalized young patients (mean age = 22.4 years) with DSM-IV schizophrenia or related disorders (N = 113) who were treated with olanzapine or risperidone. Olanzapine or risperidone was randomly prescribed for patients who were drug-naive or were treated with typical antipsychotics before admission (N = 36). Patients who had started olanzapine (N = 39) or risperidone treatment (N = 23) prior to admission continued with that medication if they showed initial clinical response. Patients who prior to admission started olanzapine (N = 6) or risperidone (N = 9) but showed no response or suffered from adverse effects switched at admission to risperidone or olanzapine, respectively. Medical records, parents, and patients revealed information on duration of treatment and compliance with olanzapine or risperidone prior to admission. The Yale-Brown Obsessive Compulsive Scale (YBOCS) was administered at admission and 6 weeks thereafter. RESULTS: At baseline and 6-week assessments, OCS were found in about 30% of 106 evaluable cases and 15% met DSM-IV criteria for obsessive-compulsive disorder. No differences in OCS were found in the patients randomly assigned to olanzapine or risperidone. The 35 subjects treated with olanzapine at both assessments had significantly (p = .01) more severe OCS at week 6 than the 20 subjects treated with risperidone at both assessments. Duration of treatment with olanzapine was significantly (p < .01) related to severity of OCS. CONCLUSION: There are no differences in the short-term propensity of olanzapine or risperidone to induce or exacerbate OCS. However, severity of OCS was associated with duration of treatment with olanzapine.

Acute Disease↗