Affect fluctuations examined with ecological momentary assessment in patients with current or remitted depression and anxiety disorders.

BACKGROUND: There is increasing interest in day-to-day affect fluctuations of patients with depressive and anxiety disorders. Few studies have compared repeated assessments of positive affect (PA) and negative affect (NA) across diagnostic groups, and fluctuation patterns were not uniformly defined. The aim of this study is to compare affect fluctuations in patients with a current episode of depressive or anxiety disorder, in remitted patients and in controls, using affect instability as a core concept but also describing other measures of variability and adjusting for possible confounders. METHODS: Ecological momentary assessment (EMA) data were obtained from 365 participants of the Netherlands Study of Depression and Anxiety with current (n = 95), remitted (n = 178) or no (n = 92) DSM-IV defined depression/anxiety disorder. For 2 weeks, five times per day, participants filled-out items on PA and NA. Affect instability was calculated as the root mean square of successive differences (RMSSD). Tests on group differences in RMSSD, within-person variance, and autocorrelation were performed, controlling for mean affect levels. RESULTS: Current depression/anxiety patients had the highest affect instability in both PA and NA, followed by remitters and then controls. Instability differences between groups remained significant when controlling for mean affect levels, but differences between current and remitted were no longer significant. CONCLUSIONS: Patients with a current disorder have higher instability of NA and PA than remitted patients and controls. Especially with regard to NA, this could be interpreted as patients with a current disorder being more sensitive to internal and external stressors and having suboptimal affect regulation.

[Involving forensic psychiatric patients in scientific research]. / De bereidheid van forensisch psychia­trische patiënten tot deelname aan wetenschappelijk onderzoek.

Background Forensic psychiatric patients are at risk to cause damage to society in the future again, both materially and immaterially. Little is known about the pharmacotherapeutic or psychotherapeutic treatment of the specific psychopathology of forensic psychiatric patients. This is possibly due to scarcity of research in the field, which could be caused by the fact that forensic psychiatric patients are often unwilling to participate in scientific research. Aim To explore the reasons why patients are unwilling to participate in research. Method Sixty-five forensic psychiatric patients were asked about their opinion on participating in pharmacological, psychotherapy, MRI- and DNA research.  Results The main reasons for not participating in pharmacological research were 'patient's belief that they will not benefit from participation in research' and 'physical integrity' (the fear of being physically harmed by participation in research). 'General resistance' (not willing to take part for no particular reason) was the main reason for not participating in psychotherapy-, MRI and DNA research.  Conclusion In order to enhance willingness to take part in research, informing the patients in the right manner with the aim of taking distrust away, would be important. Also, it could be helpful to offer a reward for participation in scientific research, although this could lead to ethical complications.

Advancing interdisciplinary research in head and neck cancer through a multicenter longitudinal prospective cohort study: the NETherlands QUality of life and BIomedical Cohort (NET-QUBIC) data warehouse and biobank.

BACKGROUND: Worldwide, over 500,000 people are diagnosed with head and neck cancer each year, a disease with major impact on life expectancy and quality of life. The purpose of the Netherlands Quality of life and Biomedical Cohort study (NET-QUBIC) is to advance interdisciplinary research that aims to optimize diagnosis, treatment, and supportive care for head and neck cancer patients and their informal caregivers. METHODS: Using an extensive assessment protocol (electronic clinical record form, patient reported outcome measures and fieldwork (interviews and physical tests)), clinical data and data on quality of life, demographic and personal factors, psychosocial (depression, anxiety, fatigue, pain, sleep, mental adjustment to cancer, posttraumatic stress), physical (speech, swallowing, oral function, malnutrition, physical fitness, neurocognitive function, sexual function), lifestyle (physical activity, nutrition, smoking, alcohol, drugs), and social factors (social function, social support, work, health care use, and costs) are collected and stored in the data warehouse. A longitudinal biobank is built with tumor tissue, blood and blood components, saliva samples, and oral rinses. An infrastructure for fieldwork and laboratory protocols is established at all participating centers. All patients fill out patient reported outcome measures before treatment and at 3, 6, 12, 24, 36, 48, and 60 months follow-up. The interviews, physical tests and biological sample collection are at baseline and 6, 12, and 24 months follow-up. The protocol for caregivers includes blood sampling and oral rinses at baseline and a tailored list of questionnaires, administered at the same time points as the patients. In total, 739 HNC patients and 262 informal caregivers have been included in 5 out of the 8 HNC centers in the Netherlands. DISCUSSION: By granting access to researchers to the NET-QUBIC data warehouse and biobank, we enable new research lines in clinical (e.g. treatment optimization in elderly patients), biological (e.g. liquid biopsy analysis for relapse detection), health related quality of life (e.g. the impact of toxicity on quality of life), and interrelated research (e.g. health related quality of life in relation to biomarkers and survival).

Correction to: Advancing interdisciplinary research in head and neck cancer through a multicenter longitudinal prospective cohort study: the NETherlands QUality of life and BIomedical Cohort (NET-QUBIC) data warehouse and biobank.

Following publication of the original article [1], the authors reported the name of R.J. Baatenburg de Jong was incorrectly tagged in the HTML version of the article.

Validity of LIDAS (LIfetime Depression Assessment Self-report): a self-report online assessment of lifetime major depressive disorder.

BACKGROUND: There is a paucity of valid, brief instruments for the assessment of lifetime major depressive disorder (MDD) that can be used in, for example, large-scale genomics, imaging or biomarker studies on depression. We developed the LIfetime Depression Assessment Self-report (LIDAS), which assesses lifetime MDD diagnosis according to DSM criteria, and is largely based on the widely used Composite International Diagnostic Interview (CIDI). Here, we tested the feasibility and determined the sensitivity and specificity for measuring lifetime MDD with this new questionnaire, with a regular CIDI as reference. METHOD: Sensitivity and specificity analyses of the online lifetime MDD questionnaire were performed in adults with (n = 177) and without (n = 87) lifetime MDD according to regular index CIDIs, selected from the Netherlands Study of Depression and Anxiety (NESDA) and Netherlands Twin Register (NTR). Feasibility was tested in an additional non-selective, population-based sample of NTR participants (n = 245). RESULTS: Of the 753 invited persons, 509 (68%) completed the LIDAS, of which 419 (82%) did this online. User-friendliness of the instrument was rated high. Median completion time was 6.2 min. Sensitivity and specificity for lifetime MDD were 85% [95% confidence interval (CI) 80-91%] and 80% (95% CI 72-89%), respectively. This LIDAS instrument gave a lifetime MDD prevalence of 20.8% in the population-based sample. CONCLUSIONS: Measuring lifetime MDD with an online instrument was feasible. Sensitivity and specificity were adequate. The instrument gave a prevalence of lifetime MDD in line with reported population prevalences. LIDAS is a promising tool for rapid determination of lifetime MDD status in large samples, such as needed for genomics studies.

Gene expression in major depressive disorder.

The search for genetic variants underlying major depressive disorder (MDD) has not yet provided firm leads to its underlying molecular biology. A complementary approach is to study gene expression in relation to MDD. We measured gene expression in peripheral blood from 1848 subjects from The Netherlands Study of Depression and Anxiety. Subjects were divided into current MDD (N=882), remitted MDD (N=635) and control (N=331) groups. MDD status and gene expression were measured again 2 years later in 414 subjects. The strongest gene expression differences were between the current MDD and control groups (129 genes at false-discovery rate, FDR<0.1). Gene expression differences across MDD status were largely unrelated to antidepressant use, inflammatory status and blood cell counts. Genes associated with MDD were enriched for interleukin-6 (IL-6)-signaling and natural killer (NK) cell pathways. We identified 13 gene expression clusters with specific clusters enriched for genes involved in NK cell activation (downregulated in current MDD, FDR=5.8 × 10(-5)) and IL-6 pathways (upregulated in current MDD, FDR=3.2 × 10(-3)). Longitudinal analyses largely confirmed results observed in the cross-sectional data. Comparisons of gene expression results to the Psychiatric Genomics Consortium (PGC) MDD genome-wide association study results revealed overlap with DVL3. In conclusion, multiple gene expression associations with MDD were identified and suggest a measurable impact of current MDD state on gene expression. Identified genes and gene clusters are enriched with immune pathways previously associated with the etiology of MDD, in line with the immune suppression and immune activation hypothesis of MDD.

Effectiveness of blended depression treatment for adults in specialised mental healthcare: study protocol for a randomised controlled trial.

BACKGROUND: Internet-based interventions are seen as an important potential strategy to improve accessibility and affordability of high quality treatments in mental healthcare. A growing number of studies have demonstrated the clinical efficacy of internet-based treatment for mood disorders, but scientific evidence for the application in routine specialised mental healthcare settings is limited. Also, little is known about the clinical and health-economic benefits of blended treatment, where online interventions are integrated with face-to-face treatment of depression in one treatment protocol. The primary aim of this study is to investigate the clinical and cost-effectiveness of blended Cognitive Behavioural Therapy (bCBT) for depression, as compared to treatment as usual (TAU) in specialised routine mental healthcare in the Netherlands. This trial is part of the E-COMPARED project which has a broader perspective, focussing on primary and specialised care in eight European countries. METHODS/DESIGN: The study is a randomised controlled non-inferiority trial with two parallel conditions: bCBT and TAU. The blended treatment combines individual face-to-face CBT with CBT delivered through an Internet-based treatment platform (Moodbuster). This platform includes a mobile phone application, used for ecological momentary assessments, automated feedback and motivational messages. Weekly alternating face-to-face (10) and online (9) sessions will be delivered over a period of 19-20 weeks. TAU is defined as the routine care that subjects receive when they are diagnosed with depression in specialised mental healthcare. Adult patients ≥ 18 years old meeting DSM-IV diagnostic criteria for major depressive disorder will be recruited within participating outpatient specialised mental healthcare clinics in the Netherlands. Measurements will be taken at baseline and at 3, 6 and 12 months follow-up. The primary outcome will be depressive symptoms, measured with the PHQ-9 and QIDS. Secondary outcomes include health-related quality of life, mastery, treatment preference, working alliance, system usability, treatment satisfaction and possible negative side-effects. Moreover, a cost-effectiveness analysis will be conducted from a societal perspective and will include both direct and indirect healthcare costs. DISCUSSION: The results of this study will provide insight into the health and economical outcomes of blended treatment for depression and give an indication of the value of implementing blended treatment in specialised clinical settings. TRIAL REGISTRATION: Netherlands Trial Register NTR4962 . Registered 05-01-2015.

The association between low vitamin D and depressive disorders.

It has been hypothesized that hypovitaminosis D is associated with depression but epidemiological evidence is limited. We investigated the association between depressive disorders and related clinical characteristics with blood concentrations of 25-hydroxyvitamin D [25(OH)D] in a large cohort. The sample consisted of participants (aged 18-65 years) from the Netherlands Study of Depression and Anxiety (NESDA) with a current (N=1102) or remitted (N=790) depressive disorder (major depressive disorder, dysthymia) defined according to DSM-IV criteria, and healthy controls (N=494). Serum levels of 25(OH)D measured and analyzed in multivariate analyses adjusting for sociodemographics, sunlight, urbanization, lifestyle and health. Of the sample, 33.6% had deficient or insufficient serum 25(OH)D (<50 nmol l(-1)). As compared with controls, lower 25(OH)D levels were found in participants with current depression (P=0.001, Cohen's d=0.21), particularly in those with the most severe symptoms (P=0.001, Cohen's d=0.44). In currently depressed persons, 25(OH)D was inversely associated with symptom severity (ß=-0.19, s.e.=0.07, P=0.003) suggesting a dose-response gradient, and with risk (relative risk=0.90, 95% confidence interval=0.82-0.99, P=0.03) of having a depressive disorders at 2-year follow-up. This large cohort study indicates that low levels of 25(OH)D were associated to the presence and severity of depressive disorder suggesting that hypovitaminosis D may represent an underlying biological vulnerability for depression. Future studies should elucidate whether-the highly prevalent-hypovitaminosis D could be cost-effectively treated as part of preventive or treatment interventions for depression.

[Complex PTSD following early-childhood trauma: emotion-regulation training as addition to the PTSD guideline]. / Complexe PTSS na vroegkinderlijk trauma: emotieregulatietraining als aanvulling op de PTSS-richtlijn.

BACKGROUND: Posttraumatic stress disorder (PTSD) symptoms in individuals who have experienced repeated trauma (sexual and/or physical) in early childhood can lead to problems associated with emotion regulation, interpersonal functioning and self-image. This so-called complex PTSD is often accompanied by a comorbid personality disorder. Although ptsd is associated with structural and functional abnormalities in emotion-regulation areas in the brain, it is not known whether complex PTSD shows similar abnormalities. Experts take the view that before individuals with complex PTSD are given appropriate therapy they should receive a course of emotion-regulation therapy such as the one tested by Zlotnick e.a. (1997) in a randomised controlled trial (RCT).   AIM: To replicate Zlotnick's RCT in the Netherlands and to find out whether complex PTSD patients show specific structural and functional brain abnormalities and whether psychological recovery is linked to the 'normalisation' of these abnormalities. METHOD: In a RCT with complex PTSD patients (n = 71) who had experienced trauma in early childhood, we compared normal individual treatment with treatment supported by 'Before and beyond', which consists of emotion-regulation therapy combined with cognitive group therapy. In a subsample (n= 33) we also performed an mri (repeated, n = 9) in which individuals were required to execute an emotional memory and attention task. RESULTS: In complex PTSD, structural abnormalities in the brain seemed to be more extensive than in PTSD and brain activity in complex PTSD seemed to be strikingly different from the brain activity seen in PTSD patients who had experienced only single trauma. The results of the RCT indicate that 'Before and beyond' is a clinically meaningful treatment (with minimal drop-out) for complex PTSD patients with a variety of personality disorders. The psychological recovery of patients who received the emotion regulation and cognitive group treatment was associated with normalisation of brain function. CONCLUSION: Treatment guidelines for ptsd patients cannot be applied directly and automatically to complex PTSD because there is no scientific evidence to justify such a step. The neurobiological profile of PTSD differs from that of complex PTSD. Patients with complex PTSD seem to react favourably to emotion regulation therapy. This treatment therefore could be a useful addition to the current PTSD guideline for this specific group. There is a need for further research that focuses on complex PTSD patients.

Age of onset in obsessive-compulsive disorder: admixture analysis with a large sample.

BACKGROUND: Research into age of onset in obsessive-compulsive disorder (OCD) has indicated significant differences between patients with early and late onset of the disorder. However, multiple criteria have been used arbitrarily for differentiating between early- and late-onset OCD, rendering inconsistent results that are difficult to interpret. METHOD: In the current study, admixture analysis was conducted in a sample of 377 OC patients to determine the number of underlying populations of age of onset and associated demographic and clinical characteristics. Various measures of anxiety, depression, co-morbidity, autism, OCD, tics and attention deficit hyperactivity disorder (ADHD) symptoms were administered. RESULTS: A bimodal age of onset was established and the best-fitting cut-off score between early and late age of onset was 20 years (early age of onset ≤19 years). Patients with early age of onset were more likely to be single. Early age of onset patients demonstrated higher levels of OCD severity and increased symptoms on all OCD dimensions along with increased ADHD symptoms and higher rates of bipolar disorder. CONCLUSIONS: It is suggested that 20 years is the recommended cut-off age for the determination of early versus late age of onset in OCD. Early age of onset is associated with a generally graver OCD clinical picture and increased ADHD symptoms and bipolar disorder rates, which may be related to greater functional implications of the disorder. We propose that age of onset could be an important marker for the subtyping of OCD.

Genome-wide association study of Tourette's syndrome.

Tourette's syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (P<5 × 10(-8)); the top signal was found in rs7868992 on chromosome 9q32 within COL27A1 (P=1.85 × 10(-6)). A secondary analysis including an additional 211 cases and 285 controls from two closely related Latin American population isolates from the Central Valley of Costa Rica and Antioquia, Colombia also identified rs7868992 as the top signal (P=3.6 × 10(-7) for the combined sample of 1496 cases and 5249 controls following imputation with 1000 Genomes data). This study lays the groundwork for the eventual identification of common TS susceptibility variants in larger cohorts and helps to provide a more complete understanding of the full genetic architecture of this disorder.

The role of negative emotionality and impulsivity in depressive/anxiety disorders and alcohol dependence.

BACKGROUND: Much is still unclear about the role of personality in the structure of common psychiatric disorders such as depressive/anxiety disorders and alcohol dependence. This study will therefore examine whether various traits of negative emotionality and impulsivity showed shared or specific associations with these disorders. Method Cross-sectional data were used from the Netherlands Study of Depression and Anxiety (NESDA), including individuals with no DSM-IV psychiatric disorder (n = 460), depressive/anxiety disorder only (i.e. depressive and/or anxiety disorder; n = 1398), alcohol dependence only (n = 32) and co-morbid depressive/anxiety disorder plus alcohol dependence (n = 358). Aspects of negative emotionality were neuroticism, hopelessness, rumination, worry and anxiety sensitivity, whereas aspects of impulsivity included disinhibition, thrill/adventure seeking, experience seeking and boredom susceptibility. RESULTS: Aspects of negative emotionality formed a homogeneous dimension, which was unrelated to the more heterogeneous construct of impulsivity. Although all aspects of negative emotionality were associated with alcohol dependence only, associations were much stronger for depressive/anxiety disorder only and co-morbid depressive/anxiety disorder with alcohol dependence. The results for impulsivity traits were less profound and more variable, with disinhibition and boredom susceptibility showing modest associations with both depressive/anxiety disorder and alcohol dependence, whereas low thrill/adventure seeking and high disinhibition were more strongly related with the first and the latter, respectively. CONCLUSIONS: Our results suggest that depressive/anxiety disorder and alcohol dependence result from shared as well as specific aetiological pathways as they showed the same associations with all aspects of negative emotionality, disinhibition and boredom susceptibility as well as specific associations with thrill/adventure seeking and disinhibition.

Genome-wide association study of major depressive disorder: new results, meta-analysis, and lessons learned.

Major depressive disorder (MDD) is a common complex disorder with a partly genetic etiology. We conducted a genome-wide association study of the MDD2000+ sample (2431 cases, 3673 screened controls and >1 M imputed single-nucleotide polymorphisms (SNPs)). No SNPs achieved genome-wide significance either in the MDD2000+ study, or in meta-analysis with two other studies totaling 5763 cases and 6901 controls. These results imply that common variants of intermediate or large effect do not have main effects in the genetic architecture of MDD. Suggestive but notable results were (a) gene-based tests suggesting roles for adenylate cyclase 3 (ADCY3, 2p23.3) and galanin (GAL, 11q13.3); published functional evidence relates both of these to MDD and serotonergic signaling; (b) support for the bipolar disorder risk variant SNP rs1006737 in CACNA1C (P=0.020, odds ratio=1.10); and (c) lack of support for rs2251219, a SNP identified in a meta-analysis of affective disorder studies (P=0.51). We estimate that sample sizes 1.8- to 2.4-fold greater are needed for association studies of MDD compared with those for schizophrenia to detect variants that explain the same proportion of total variance in liability. Larger study cohorts characterized for genetic and environmental risk factors accumulated prospectively are likely to be needed to dissect more fully the etiology of MDD.

Theory of Mind differences in older patients with early-onset and late-onset paranoid schizophrenia.

OBJECTIVE: Theory of Mind (ToM) is considered an essential element of social cognition. In younger schizophrenia patients, ToM impairments have extensively been demonstrated. It is not clear whether similar impairments can be found in older schizophrenia patients and if these impairments differ between older patients with early-onset and late-onset schizophrenia. METHODS: Theory of Mind abilities were assessed using the Hinting Task in 15 older patients (age 60 years and older) with early-onset paranoid schizophrenia, 15 older patients with late-onset paranoid schizophrenia and 30 healthy controls. ANCOVA was performed to test differences between groups. Analyses were adjusted for level of education. Effect sizes, partial eta squared (ε(2) ), were computed as an indication of the clinical relevance of the findings. RESULTS: Patients with early-onset schizophrenia scored significantly lower on the Hinting Task (mean 16.1; SD 4.3) compared with patients with late-onset schizophrenia (mean 18.6; SD 1.5) and with healthy controls (mean 19.0; SD 1.4). The effect size of this difference was large (ε(2) = 0.2). CONCLUSIONS: These results suggest that ToM functioning may be a protective factor modulating the age at onset of psychosis. Further studies into the relationship between social cognition and onset age of psychosis are warranted.

Treatment effects on insular and anterior cingulate cortex activation during classic and emotional Stroop interference in child abuse-related complex post-traumatic stress disorder.

BACKGROUND: Functional neuroimaging studies have shown increased Stroop interference coupled with altered anterior cingulate cortex (ACC) and insula activation in post-traumatic stress disorder (PTSD). These brain areas are associated with error detection and emotional arousal. There is some evidence that treatment can normalize these activation patterns. METHOD: At baseline, we compared classic and emotional Stroop performance and blood oxygenation level-dependent responses (functional magnetic resonance imaging) of 29 child abuse-related complex PTSD patients with 22 non-trauma-exposed healthy controls. In 16 of these patients, we studied treatment effects of psycho-educational and cognitive behavioural stabilizing group treatment (experimental treatment; EXP) added to treatment as usual (TAU) versus TAU only, and correlations with clinical improvement. RESULTS: At baseline, complex PTSD patients showed a trend for increased left anterior insula and dorsal ACC activation in the classic Stroop task. Only EXP patients showed decreased dorsal ACC and left anterior insula activation after treatment. In the emotional Stroop contrasts, clinical improvement was associated with decreased dorsal ACC activation and decreased left anterior insula activation. CONCLUSIONS: We found further evidence that successful treatment in child abuse-related complex PTSD is associated with functional changes in the ACC and insula, which may be due to improved selective attention and lower emotional arousal, indicating greater cognitive control over PTSD symptoms.

[ROM in adult psychiatry: an evaluation of measurement instruments]. / ROM in de volwassenenpsychiatrie: een evaluatie van meetinstrumenten.

BACKGROUND: An evaluation of the most commonly used ROM measures in Dutch psychiatry is lacking, both for severe mental illnesses and for common psychiatric disorders. AIM: To provide an overview of the characteristics and quality of outcome measures. METHOD: A literature study yielded six outcome measures. The psychometrical, clinical and practical aspects of these scales are described. RESULTS: The measures are suitable and are of adequate quality. DISCUSSION: It remains to be seen if any of the outcome measures are suitable for both serious and less serious mental illnesses. The use of a combination of a self-rating scale and an observerrating scale that measure symptoms and domains of functioning may be the most promising choice.

[A study of job satisfaction among Dutch psychiatrists]. / Een onderzoek naar arbeidssatisfactie onder Nederlandse psychiaters.

BACKGROUND: Psychiatrists in the Netherlands seem to be experiencing more and more work stress and consequently less job satisfaction. Little research has been done in this field and the situation needs to be further investigated. AIM: To obtain insight into the degree of job satisfaction experienced by Dutch psychiatrists and into factors that influence their job satisfaction. METHOD: 2489 Dutch psychiatrists were asked to participate in a written enquiry. RESULTS: psychiatrists responded; of these, 852 responses were complete. The age, sex and years of experience of the respondents seemed to be largely representative for Dutch psychiatrists in general. Psychiatrists in the Netherlands seemed to be reasonably satisfied with their work, but they also experienced a considerable amount of work stress. In particular, it was organisationrelated work stress that reduced their job satisfaction. This pattern does not differ essentially from the pattern that exists in other countries or among representatives of other specialisms. In the Netherlands, however, the work setting is particularly significant. CONCLUSION: There seems to be a discrepancy between the relatively positive job satisfaction of Dutch psychiatrists and the high level of stress they experience as a result of working conditions. This situation is having a detrimental effect on job satisfaction. The implication is therefore that a number of managerial and policy measures need to be taken at various levels.

[Validation of two measuring instruments for routine outcome monitoring in psychiatry: the HORVAN study]. / Validering van twee meetinstrumenten voor routine outcome monitoring in de psychiatrie: de HORVAN-studie.

BACKGROUND: Transparency in psychiatry can be increased by the use of routine outcome monitoring (rom) instruments. Instruments should be easy to use and take very little time to complete; they also need to have psychometric qualities, be sensitive to change, and provide information about patients' symptoms, and about interpersonal and social functioning. AIM: To investigate to what extent the combination of Health of the Nation Outcome Scales (HoNOS) and the Outcome Questionnaire (OQ) in the Dutch situation meets the above-mentioned quality criteria and to examine how the combination relates to the Symptom CheckList (SCL-­90). METHOD: Data for 148 patients collected at three measurement moments were available for analysis. The psychometric qualities of the instruments and their sensitivity to change were checked carefully. RESULTS: The three scales showed high values for internal consistency (Cronbach's alpha). The HoNOS total score and the subscales of the OQ correlated reasonably well with the SCL­-90 total score (convergence validity). At the first measurements, patients with a comorbid diagnosis had the lowest scores (discrimination validity). The clinically significant change between T1 and T2 and between T2 and T3 was sufficiently high for all three measuring instruments. CONCLUSION: The combination of the HoNOS rating scale and the self­-report list OQ seems to be suitable for ROM in psychiatry.

[The immune system and Alzheimer's disease]. / Het immuunsysteem en de ziekte van Alzheimer.

BACKGROUND: It has still not been established unequivocally whether vascular risk factors and inflammatory reactions, determined by heredity, are a cause or a result of Alzheimer's disease AIM: If the offspring of parents with AD have more risk factors and more frequent and severe inflammatory reactions than the offspring of parents without AD , this argues strongly in favor of a causal relationship between vascular risk factors, a pro-inflammatory cytokine response and AD. AIM: To determine whether the offspring of parents with ad have more risk factors and more frequent and severe inflammatory reactions than the offspring of parents without ad. method Vascular risk-factors, pro-inflammatory cytokines and the apoe genotype were determined in 206 offspring of parents with ad and in 200 offspring of parents without AD. RESULTS: Offspring of parents with ad carried more apoe epsilon4 than offspring of parents without ad (47% vs 21%). Middle-aged offspring of parents with a history of ad also had higher blood pressure and a greater atherosclerotic burden than the offspring of parents without AD. Also their response to the pro-inflammatory cytokine was significantly higher. CONCLUSION: Hypertension and an inherited pro-inflammatory cytokine profile in middle age are early risk factors that contribute to the development of ad in old age. Offspring with a parental history of AD should therefore be offered screening and treatment for hypertension and have their blood pressure checked so that the development of AD in old age can be prevented.