[show abstract][hide abstract] ABSTRACT: To assess the effect of withdrawal of antipsychotic treatment on relapse risk in remitted first-episode schizophrenia patients.
First-episode 1-year stable and remitted outpatients with a schizophrenic disorder were randomly allocated to continuation of their antipsychotic regimen for at least 6 months (N = 9), or gradual withdrawal (N = 11). Primary outcome was the difference in cumulative relapse-free survival at 9 months.
Recruitment was terminated prematurely on 26 October 2005. The cumulative relapse-free survival was 88% (SE = 0.12) in the continuation and 18% (SE = 0.12) in the discontinuation group (P = 0.001) at 9 months follow-up.
Discontinuation of antipsychotic medication markedly increases the risk of relapse in stable remitted first-episode schizophrenia patients. In future studies the topics of safety monitoring and sampling of patients should receive extra attention.
International Journal of Psychiatry in Clinical Practice 06/2011; 15(2):128-34. · 0.45 Impact Factor
[show abstract][hide abstract] ABSTRACT: Infections have been suggested to play a role in the etiology of schizophrenia, but the evidence for this has been inconsistent. Schizophrenia patients have an increased risk of infections as a result of hospitalizations or life style factors. Therefore a study on early subclinical manifestations of psychosis in relation to virus infections is warranted. We examined whether serum antibodies against human Herpes viruses and Toxoplasma gondii were associated with subclinical symptoms of psychosis in adolescents. Data were collected as part of the TRacking Adolescents' Individual Lives Survey (TRAILS) cohort, a large prospective cohort of Dutch adolescents. A total of 1176 participants with an available Community Assessment of Psychic Experiences (CAPE) and an available blood sample were included in this analysis. Solid-enzyme immunoassay methods were used to measure the presence of immunoglobulin G (IgG) antibodies in serum to the Herpes virus family and to T. gondii. There was no significant association between serologic evidence of infection with human Herpes viruses or T. gondii and the risk of subclinical positive experience of psychosis. Subjects with a positive serological reaction to Epstein-Barr Virus (EBV) had higher scores on the positive dimension of psychosis measured by CAPE (b=0.03, P=0.02). This significant association was observed in males, but not in females. The current study suggests that there is no significant association between serological evidence of infection to human Herpes viruses and positive subclinical experience of psychosis, whereas there was an association between EBV infection and subclinical psychotic symptoms in boys.
Schizophrenia Research 03/2011; 129(1):47-51. · 4.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: Weight gain is one of the major problems in patients using antipsychotic medication, leading to relevant morbidities and reduced compliance to pharmacotherapy. Recently, an association has been reported between a single nucleotide polymorphism (rs1455832) of the roundabout axon guidance receptor, homolog 1 (ROBO1) gene and body mass index (BMI) in persons younger than 30 years. The aim of this study is to investigate the association between BMI and rs1455832 in patients with a psychotic disorder using antipsychotics.
A cross-sectional design was used in a pooled sample of Caucasian psychiatric patients obtained from three comparable Dutch psychiatric populations. Patients were eligible for inclusion in this study if they met the Diagnostic and Statistical Manual of Mental Disorders-IV criteria for a nonaffective psychotic disorder, were 18 years or older, and used one or more antipsychotics. Genotyping was performed according to standard protocols. Linear (for BMI) and logistic (for obesity, defined as BMI > 30) regression analyses, corrected for age and sex, were applied in the statistical analyses.
A total of 435 patients were included in this association analyses. The rs1455832 polymorphism studied was significantly associated with BMI and obesity in female patients. Female patients had a statistically significant (P = 0.025) decrease of 1.76 kg/m in BMI values per C allele. In contrast to female patients, this association was not exhibited in male patients.
The rs1455832 polymorphism may play a role in inducing obesity in female patients using antipsychotics.
[show abstract][hide abstract] ABSTRACT: Antidepressants are frequently prescribed in patients with psychotic disorders, but little is known about their effects in routine clinical practice. The objective was to investigate the prescribing patterns of antidepressants in relation to the course of depressive symptoms in patients with psychotic disorders.
A cohort of 214 Dutch patients with psychotic disorders received two assessments of somatic and psychiatric health, including a clinician-rated screening for depressive symptoms, as part of annual routine outcome monitoring.
Depressive symptoms were prevalent among 43% (93) of the patients. Antidepressants were prescribed for 40% (86) of the patients and the majority 83% (71) continued this therapy after one year. Multivariable analysis showed that patients with more severe psychopathology had a higher risk to develop depressive symptoms the following year (OR [95% CI]=0.953 [0.912-0.995]). For patients with depressive symptoms at baseline, polypharmacy was a potential risk factor to keep having depressive symptoms (OR [95% CI]=1.593 [1.123-2.261]). Antidepressant use was not an independent predictor in both analyses.
Routine outcome monitoring in patients with psychotic disorders revealed a high prevalence of depressive symptoms. Antidepressants were frequently prescribed and continued in routine clinical practice.
European Psychiatry 02/2011; 27(4):240-4. · 3.29 Impact Factor
[show abstract][hide abstract] ABSTRACT: Antipsychotic affinity for the histamine H1 receptor and the muscarinic M3 receptor have been associated with the side effects weight gain, and development of diabetes, respectively.
We investigated polymorphisms of the histamine H1 (HRH1) and muscarinic acetylcholine receptor M3 (CHRM3) receptor genes for an association with body mass index (BMI) and glycated hemoglobin (HbA1c).
We included 430 Caucasian patients with a non-affective psychotic disorder using antipsychotics for at least 3 months. Primary endpoints of the study were cross-sectionally measured BMI and HbA1c; secondary endpoints were obesity and hyperglycaemia. Two single-nucleotide polymorphisms (SNPs) in the HRH1 gene, rs346074 and rs346070, and one SNP in the CHRM3 gene, rs3738435, were genotyped. Our primary hypothesis in this study was an interaction between genotype on BMI and antipsychotic affinity for the H1 and M3 receptor.
A significant association of interaction between haplotype rs346074-rs346070 and BMI (p value 0.025) and obesity (p value 0.005) in patients using high-H1 affinity antipsychotics versus patients using low-H1 affinity antipsychotics was found. There was no association of CHRM3 gene variant rs3738435 with BMI, and we observed no association with HbA1c or hyperglycaemia in any of the variants.
This study, for the first time, demonstrates a significant association between HRH1 variants and BMI in patients with a psychotic disorder using antipsychotics. In future, genotyping of HRH1 variants may help predicting weight gain in patients using antipsychotics.
[show abstract][hide abstract] ABSTRACT: Antipsychotics are approved treatment for severe conditions and have serious side effects. Antipsychotics are often prescribed off-label. Although a substantial proportion of antipsychotics are prescribed in primary care, it is largely unknown what motivates the general practitioner (GP) to initiate antipsychotic treatment. Therefore, we sought to examine the relation between pre-defined, licensed as well as off-label, reasons for antipsychotic treatment and the initiation of this treatment by the GP as well as report registration and incidence of antipsychotic treatment in general practice.
In a case-control study, 723 patients selected from an electronic database and with a new antipsychotic prescription were compared with 3615 controls receiving any other new prescription. Using logistic regression, six pre-defined categories of International Classification of Primary Care (ICPC) codes ('psychosis', 'depression and anxiety', 'sleeping disorders', 'acute stress and surmenage', 'dementia' and 'somatic indications') were associated with initiating antipsychotic treatment.
All, including off-label, categories were significantly related to initiating antipsychotic treatment. The incidence of initiating antipsychotic therapy was 1.28 per 1000 persons per year (95% confidence interval: 1.09, 1.48). GPs registered an ICPC code in 50% and prescribed typical antipsychotics in 90% of the cases. Prescription of atypical antipsychotics increased almost threefold over the study period.
The results suggest that GPs prescribe antipsychotics off-label. Despite serious side effects and relatively infrequent occurrence in Dutch general practices, GPs seem imprecise in underpinning and registrating the initiation of antipsychotic treatment. GPs increasingly prescribe atypical antipsychotics although the prescription of typical antipsychotics still dominates.
Journal of Evaluation in Clinical Practice 02/2011; 17(1):12-7. · 1.51 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate the association between cognitive complaints and objective cognitive functioning in bipolar patients, with a focus on the moderating role of depressive symptoms.
The association between cognitive complaints (measured by the total score and four subscales of the Cognitive Failure Questionnaire; CFQ) and objective cognitive functioning (domains of psychomotor speed, speed of information processing, attentional switching, verbal memory, visual memory and executive functioning/working memory, and the total score) was assessed in 108 euthymic (n=45) or mildly to moderately depressed bipolar patients (n=63). We studied potential moderation of this association by depressive symptoms (total score of the Inventory of Depressive Symptomatology-self rating). Analyses were performed using Pearson correlations and multiple linear regression.
Cognitive complaints were not associated with objective cognitive functioning, except for CFQ 'memory for names' which was positively correlated with speed of information processing (r=0.257, p=0.007). Although depressive symptoms were positively associated with cognitive complaints (total score and three subscales; p<0.01), the association between cognitive complaints and objective cognitive functioning was not moderated by depressive symptoms (p for interaction 0.054 to 0.988).
It can be argued whether the retrospective questionnaire (CFQ) is sufficiently accurate to measure the type of cognitive dysfunctions seen in bipolar patients.
Cognitive complaints are not associated with objective cognitive functioning, irrespective of depressive symptoms. However, cognitive complaints are indicative for depressive symptoms. Clinicians should be to be alert to depressive symptoms rather than objective cognitive problems in patients expressing cognitive complaints.
Journal of affective disorders 02/2011; 130(1-2):306-11. · 3.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: The influence of antipsychotic medication on brain morphology in schizophrenia may confound interpretation of brain changes over time. We aimed to assess the effect of discontinuation of atypical antipsychotic medication on change in brain volume in patients. Sixteen remitted, stable patients with first-episode schizophrenia, schizoaffective or schizophreniform disorder and 20 healthy controls were included. Two magnetic resonance imaging brain scans were obtained from all subjects with a 1-year interval. The patients either discontinued (n = 8) their atypical antipsychotic medication (olanzapine, risperidone, or quetiapine) or did not (n = 8) discontinue during the follow-up period. Intracranial volume and volumes of total brain, cerebral gray and white matter, cerebellum, third and lateral ventricle, nucleus caudatus, nucleus accumbens, and putamen were obtained. Multiple linear regression analyses were used to assess main effects for group (patient-control) and discontinuation (yes-no) for brain volume (change) while correcting for age, sex, and intracranial volume. Decrease in cerebral gray matter and caudate nucleus volume over time was significantly more pronounced in patients relative to controls. Our data suggest decreases in the nucleus accumbens and putamen volumes during the interval in patients who discontinued antipsychotic medication, whereas increases were found in patients who continued their antipsychotics. We confirmed earlier findings of excessive gray matter volume decrements in patients with schizophrenia compared with normal controls. We found evidence suggestive of decreasing volumes of the putamen and nucleus accumbens over time after discontinuation of medication. This might suggest that discontinuation reverses effects of atypical medication.
Journal of clinical psychopharmacology 02/2011; 31(2):146-53. · 5.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: The present study examined construct equivalence of the teacher Strengths and Difficulties Questionnaire and compared mean scores in an ethnically diverse sample of children living in the Netherlands. Elementary schoolteachers completed the Strengths and Difficulties Questionnaire for 2,185 children aged 6 to 10 years of the four largest ethnic groups in the Netherlands, namely native Dutch (n = 684) and Moroccan (n = 702), Turkish (n = 434), and Surinamese (n = 365) immigrant children. Multigroup confirmatory factor analysis suggested the factor structure of the Strengths and Difficulties Questionnaire to be invariant across children’s ethnicity and gender. Additionally, the factor structure appeared to be similar for Dutch and Surinamese teachers. However, mean scores on emotional problems, hyperactivity, conduct problems, prosocial behavior, and impairment varied significantly according to ethnicity and gender. Mean scores on peer problems differed significantly for boys and girls, but not across ethnicity. Whether mean differences reflect a method bias or actual differences in classroom behaviors is discussed and needs further research.
Journal of Cross-Cultural Psychology 01/2011; 42(3):466-481. · 1.42 Impact Factor
[show abstract][hide abstract] ABSTRACT: Grief interventions are more effective for high risk individuals. The presence of suicide ideation following suicide bereavement was examined to determine whether it indicates a high risk status. Using data from a randomized controlled trial (n = 122) on the effectiveness of cognitive-behavior therapy, the effect of suicide ideation on the effectiveness of grief therapy on the bereavement outcome at 13 months post loss was examined. Results show that suicide ideators more often have a history of mental disorder and suicidal behavior than non-ideators, and suicide ideation indicates a high risk for adverse bereavement outcome. Grief therapy likely reduces the risk of maladaptive grief reactions among suicide ideators. Therefore, suicide ideators may benefit from grief therapy following a loss through suicide.
Suicide and Life-Threatening Behavior 10/2010; 40(5):425-37. · 1.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate associations between different indices of family socioeconomic position (SEP) and the use of specialty mental health services (SMHS) and whether the associations exist after adjusting for severity of mental problems.
Using data from a large longitudinal study of adolescents (N = 2,149; mean age = 13.6 years [SD = 0.53, range = 12 to 15 years]; 51% girls), we assessed the relations of family SEP indices with SMHS use while accounting for severity of mental problems in logistic regression models. Multiple informants (parent, self, and teachers) assessed severity of mental health problems using the Achenbach scales. A parent questionnaire was used to assess family SEP (parents' education, parents' occupation, and family income) and SMHS use. Baseline response rate was 76%, and 96.4% of responders were reassessed at a 2.5-year follow-up visit. Baseline assessments ran from March 2001 through July 2002 and follow-up from September 2003 to December 2004.
Overall, 6.7% of the total sample and 42.9% of those with mental problems accessed SMHS. Univariable analyses yielded no significant associations between SMHS and all the indices of SEP. Adjustment for the severity of mental problems resulted in substantial and statistically significant associations of indices of SEP with SMHS use. Adolescents were particularly more likely to use SMHS with increasing levels of maternal education. Compared to mothers with elementary education, those with university education were three times more likely to consult SMHS independent of severity of their offspring's mental health problems (odds ratio [OR] = 3.18, confidence interval [CI] = 1.22, 8.30). For the aggregate measure of SEP, high SEP was associated with increased use of SMHS compared with low SEP (OR = 1.63, CI = 1.04, 2.55).
Higher levels of maternal education and overall SEP predict more SMHS use when the severity of mental problems was accounted for. Without correcting for the severity of mental problems, the true association between SEP and SMHS use is obscured in early adolescents.
Journal of the American Academy of Child and Adolescent Psychiatry 07/2010; 49(7):647-55. · 4.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: Inflammatory processes may play a role in the pathophysiology of schizophrenia. The aim of this study was to determine the efficacy of adjuvant treatment with aspirin (acetylsalicylic acid) in schizophrenia spectrum disorders.
This randomized, double-blind, placebo-controlled study was conducted between May 2004 and August 2007. Seventy antipsychotic-treated inpatients and outpatients from 10 psychiatric hospitals in The Netherlands with a DSM-IV-diagnosed schizophrenia spectrum disorder were included. Patients were randomized to adjuvant treatment with aspirin 1000 mg/d or placebo. During a 3-month follow-up, psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS). Other assessments included cognitive tests and immune function. The primary efficacy outcome was the change in total PANSS score. Secondary outcomes were changes in the PANSS subscales and cognitive test results.
Mixed-effect models showed a 4.86-point (95% CI, 0.91 to 8.80) and 1.57-point (95% CI, 0.06 to 3.07) larger decrease in the aspirin group compared to the placebo group on the total and positive PANSS score, respectively. Similar but not statistically significant results were observed for the other PANSS subscale scores. Treatment efficacy on total PANSS score was substantially larger in patients with the more altered immune function (P = .018). Aspirin did not significantly affect cognitive function. No substantial side effects were recorded.
Aspirin given as adjuvant therapy to regular antipsychotic treatment reduces the symptoms of schizophrenia spectrum disorders. The reduction is more pronounced in those with the more altered immune function. Inflammation may constitute a potential new target for antipsychotic drug development.
controlled-trials.com Identifier: ISRCTN27745631.
The Journal of Clinical Psychiatry 05/2010; 71(5):520-7. · 5.81 Impact Factor
[show abstract][hide abstract] ABSTRACT: Cognitive dysfunction is clearly recognized in bipolar patients, but the degree of impairment varies due to methodological factors as well as heterogeneity in patient populations. The goal of this study was to evaluate cognitive functioning in bipolar patients and to assess its association with depressive symptoms. Post hoc the relationship with lifetime alcohol use disorder was explored.
The study included 110 bipolar patients and 75 healthy controls. Patients with severe depressive symptoms, (hypo)manic symptoms and current severe alcohol use disorder were excluded. Diagnoses were evaluated via the Mini-International Neuropsychiatric Interview. Cognitive functioning was measured in domains of psychomotor speed, speed of information processing, attentional switching, verbal memory, visual memory, executive functioning and an overall mean score. Severity of depression was assessed by the Inventory of Depressive Symptomatology-self rating. Patients were euthymic (n = 46) or with current mild (n = 38) or moderate (n = 26) depressive symptoms. Cognitive impairment was found in 26% (z-score 2 or more above reference control group for at least one domain) of patients, most prominent in executive functioning (effect size; ES 0.49) and speed of information processing (ES 0.47). Depressive symptoms were associated with dysfunction in psychomotor speed (adjusted beta 0.43; R(2) 7%), speed of information processing (adjusted beta 0.36; R(2) 20%), attentional switching (adjusted beta 0.24; R(2) 16%) and the mean score (adjusted beta 0.23; R(2) 24%), but not with verbal and visual memory and executive functioning. Depressive symptoms explained 24% of the variance in the mean z-score of all 6 cognitive domains. Comorbid lifetime alcohol use (n = 21) was not associated with cognitive dysfunction.
Cognitive dysfunction in bipolar disorder is more severe in patients with depressive symptoms, especially regarding speed and attention. Therefore, interpretation of cognitive functioning in patients with depressive symptoms should be cautious. No association was found between cognitive functioning and lifetime comorbid alcohol use disorder.
[show abstract][hide abstract] ABSTRACT: The link between physical conditions and mental health is poorly understood. Functional disability could explain the association of physical conditions with major depressive episode (MDE) as an intermediary factor.
Data was analyzed from a subsample (N=8796) of the European Study of the Epidemiology of Mental Disorders (ESEMeD), a cross-sectional general population survey. MDE during the last 12 months was assessed using a revision of the Composite International Diagnostic Interview (CIDI 3.0). Lifetime chronic physical conditions were assessed by self-report. Functional disability was measured using a version of the World Health Organization Disability Assessment Schedule (WHODAS). The associations of physical conditions with MDE and explanation by functional disability were quantified using logistic regression.
All physical conditions were significantly associated with MDE. The increases in risk of MDE ranged from 30% for allergy to amply 100% for arthritis and heart disease. When adjusted for physical comorbidity, associations decreased and were no longer statistically significant for allergy and diabetes. Functional disability explained between 17 and 64% of these associations, most substantially for stomach or duodenum ulcer, arthritis and heart disease.
Due to the cross-sectional nature of the study the temporal relationship of the variables could not be assessed and the amount of explanation cannot simply be interpreted as the amount of mediation.
Our findings suggest that the association of chronic physical conditions with MDE is partly explained by functional disability. Such explanation is more pronounced for pain causing conditions and heart disease. Health professionals should be particularly aware of the increased risk of depressive disorder when patients experience disability from these conditions.
Journal of affective disorders 11/2009; 124(1-2):38-44. · 3.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: Familial risk factors have been implicated in the development of mental health problems in adolescents. Whether the associations between parental loading, as assessed by lifetime psychopathology, and offspring internalising and externalising problems were moderated by family socioeconomic position (SEP) was investigated. Two hypotheses of moderation were tested: (1) the "social push" hypothesis in which parental loading effects are stronger in contexts with low environmental risks and (2) the "vulnerability" hypothesis in which parental loading effects are stronger in high-risk environments.
In a population-based sample of 2149, familial loading and family SEP were assessed at baseline by parent reports. Offspring psychopathology was assessed by reports from multiple informants (parent, self and teachers). Multiple linear regression was used to assess the independent associations of parental loading and family SEP on offspring psychopathology and their potential interaction.
Both family SEP and familial loading had significant independent main effects on offspring internalising and externalising problems. However, the interaction terms were not significant and did not add any explanatory power to the model.
Lower levels of family SEP appear not to confer additional risks for mental health problems in offspring of parents with high loading on psychopathology. During early adolescence, parental psychopathology and low family SEP seem independent risk factors for offspring mental health problems. Results do not support either the social push or vulnerability hypothesis as no evidence of interactions between parental loading and family SEP were found.
Journal of epidemiology and community health 10/2009; 65(1):57-63. · 3.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: Data about follow-up after acute pharmacological treatment of psychotic depression are scarce.
A 4 month open follow-up was done, preferentially with same medication as during acute treatment, of patients (n=59) with DSM-IV-TR major depressive disorder with psychotic features, aged 18 to 65 years, who had completed as responders an acute double-blind 7 week trial with imipramine, venlafaxine or venlafaxine plus quetiapine. Main outcome measures were Hamilton Rating Scale for Depression and Clinical Global Impression Scale.
Six patients dropped out during the 4 month follow-up. Almost all patients (86.4%; 51/59) remained responder while remission rate increased from 59.3% (35/59) to 86.8% (46/53), independent of treatment. Relapse rate was low (3.8%; 2/53). Tolerability was good. Weight increased with all treatments.
Limitations were the limited sample size and consequent limited statistical power. The treatment during follow-up was not double-blind.
Continuation treatment with the same medication that was effective in the acute treatment trial, remained effective during the 4 month follow-up in many patients leading to further improvement, and was well tolerated.
Journal of affective disorders 10/2009; 123(1-3):238-42. · 3.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: Life stressors and family socioeconomic position have often been associated with mental health status. The aim of the present study is to contribute to the understanding of the pathways from low socioeconomic position and life stressors to mental problems.
In a cross-sectional analysis using data from a longitudinal study of early adolescents (N = 2,149, 51% girls; mean age 13.6 years, SD 0.53, range 12-15), we assessed the extent of mediation of the association between family socioeconomic position and mental health problems by different types of life stressors in multiple regression models. Stressors were rated as environment related or person related. Information on socioeconomic position was obtained directly from parents, and internalizing and externalizing problem behaviors were assessed by reports from multiple informants (parents, self, and teachers).
Low socioeconomic position was associated with more mental health problems and more life stressors. Both environment-related and person-related stressors predicted mental health problems independently of socioeconomic position. The associations between socioeconomic position and all mental health outcomes were partly mediated by environment-related life stressors. Mediation by environment-related and person-related stressors as assessed by linear regression amounted to 56% (95% confidence interval [CI] 35%-78%) and 7% (95% CI -25% to 38%) for internalizing problems and 13% (95% CI 7%-19%) and 5% (95% CI -2% to 13%) for externalizing problems, respectively.
Environment-related, but not person-related, stressors partly mediated the association between socio economic position and adolescent mental problems. The extent of mediation was larger for internalizing than for externalizing problems. Because the effect sizes of the associations were relatively small, targeted interventions to prevent impaired mental health may have only modest benefits to adolescents from low socioeconomic background.
Journal of the American Academy of Child and Adolescent Psychiatry 09/2009; 48(10):1031-8. · 4.98 Impact Factor