R. van Dyck

The Netherlands Study of Depression and Anxiety (NESDA): rationale, objectives and methods.

The Netherlands Study of Depression and Anxiety (NESDA) is a multi‐site naturalistic cohort study to: (1) describe the long‐term course and consequences of depressive and anxiety disorders, and (2) to integrate biological and psychosocial research paradigms within an epidemiological approach in order to examine (interaction between) predictors of the long‐term course and consequences.

Genome-wide association for major depressive disorder: a possible role for the presynaptic protein piccolo

Major depressive disorder (MDD) is a common complex trait with enormous public health significance. As part of the Genetic Association Information Network initiative of the US Foundation for the National Institutes of Health, we conducted a genome-wide association study of 435 291 single nucleotide polymorphisms (SNPs) genotyped in 1738 MDD cases and 1802 controls selected to be at low liability for MDD. Of the top 200, 11 signals localized to a 167 kb region overlapping the gene piccolo (PCLO, whose protein product localizes to the cytomatrix of the presynaptic active zone and is important in monoaminergic neurotransmission in the brain) with P-values of 7.7 × 10−7 for rs2715148 and 1.2 × 10−6 for rs2522833. We undertook replication of SNPs in this region in five independent samples (6079 MDD independent cases and 5893 controls) but no SNP exceeded the replication significance threshold when all replication samples were analyzed together. However, there was heterogeneity in the replication samples, and secondary analysis of the original sample with the sample of greatest similarity yielded P=6.4 × 10−8 for the nonsynonymous SNP rs2522833 that gives rise to a serine to alanine substitution near a C2 calcium-binding domain of the PCLO protein. With the integrated replication effort, we present a specific hypothesis for further studies.

Consequences of anxiety in older persons: its effect on disability, well-being and use of health services

BACKGROUND Although anxiety is quite prevalent in late life, its impact on disability, well-being, and health care utilization of older persons has not been studied. Older persons are a highly relevant age group for studying the consequences of anxiety, since their increasing numbers put an extra strain on already limited health care resources. METHODS Data of a large community-based random probability sample (N = 659) of older subjects (55-85 year) in the Netherlands were used to select three groups: subjects with a diagnosed anxiety disorder, subjects with merely anxiety symptoms and a reference group without anxiety. These groups were compared with regard to their functioning, subjective well-being, and use of health care services, while controlling for potentially confounding variables. RESULTS Anxiety was associated with increased disability and diminished well-being. Older persons with a diagnosed anxiety disorder were equally affected in their functioning as those with merely anxiety symptoms. Although use of health services was increased in anxiety sufferers, their use of appropriate care was generally low. CONCLUSIONS Anxiety has a clear negative impact on the functioning and well-being of older subjects. The similarity of participants with an anxiety disorder and those having merely anxiety symptoms regarding quality of life variables and health care use was quite striking. Finally, in spite of its grave consequences for the quality of life, appropriate care for anxiety is seldom received. Efforts to improve recognition, disseminate effective treatments in primary care, and referring to specialized care may have positive effects on the management of anxiety in late life.

A meta-analysis on the treatment of obsessive compulsive disorder: A comparison of antidepressants, behavior, and cognitive therapy

A meta-analysis was conducted to integrate treatment results from outcome research on the efficacy of antidepressants, behavior therapy, cognitive therapy, and the combination of these methods in obsessive compulsive disorder. The effect sizes for self-rated obsessive compulsive symptoms were found to be significantly smaller than for assessor-ratings. Because of the lack of overlap in use of measurement instruments in the respective studies, no common measurement instrument could be selected. Therefore, analyses were performed on both self- and assessor-ratings. On self- and assessor-rated obsessive-compulsive symptoms, the serotonergic antidepressants clomipramine, Fluoxetine, and fluvoxamine, behavior therapy, and the combination of serotonergic antidepressants with behavior therapy were significantly more effective than placebo treatment. Although scarce, follow-up data from 3 months to 6 years indicated that the short-term treatment effects remain stable. On self-ratings, behavior therapy was significantly more effective than serotonergic antidepressants. The combination treatment tended to be more effective than serotonergic antidepressants. On assessor-ratings, however, no difference could be demonstrated between these three treatments. Future research on antidepressants and behavior therapy should adopt the same standards for self and assessor-ratings. Moreover, research should focus on long-term efficacy of treatments offered.

The co-morbidity of anxiety and depression in the perspective of genetic epidemiology. A review of twin and family studies

BACKGROUND Co-morbidity within anxiety disorders, and between anxiety disorders and depression, is common. According to the theory of Gray and McNaughton, this co-morbidity is caused by recursive interconnections linking the brain regions involved in fear, anxiety and panic and by heritable personality traits such as neuroticism. In other words, co-morbidity can be explained by one disorder being an epiphenomenon of the other and by a partly shared genetic etiology. The aim of this paper is to evaluate the theory of Gray and McNaughton using the results of genetic epidemiological studies. METHOD Twenty-three twin studies and 12 family studies on co-morbidity are reviewed. To compare the outcomes systematically, genetic and environmental correlations between disorders are calculated for the twin studies and the results from the family studies are summarized according to the method of Klein and Riso. RESULTS Twin studies show that co-morbidity within anxiety disorders and between anxiety disorders and depression is explained by a shared genetic vulnerability for both disorders. Some family studies support this conclusion, but others suggest that co-morbidity is due to one disorder being an epiphenomenon of the other. CONCLUSIONS Discrepancies between the twin and family studies seem partly due to differences in used methodology. The theory of Gray and McNaughton that neuroticism is a shared risk factor for anxiety and depression is supported. Further research should reveal the role of recursive interconnections linking brain regions. A model is proposed to simultaneously investigate the influence of neuroticism and recursive interconnections on co-morbidity.

Psychiatric comorbidity in epilepsy

Many studies on psychiatric comorbidity in epilepsy have been performed using many different patient groups and diagnostic instruments. This methodological heterogeneity complicates comparison of the findings. In this article, psychiatric disorders in epilepsy are reviewed from the perspective of the DSM classification system. The empirical findings of axis I clinical disorders and axis II personality disorders are described separately. Furthermore, the existence and specificity of conditions such as interictal dysphoric disorder, interictal behavior syndrome, and psychosis of epilepsy are discussed. From the many studies that have been performed on this topic it can be learned that there is a need for well-controlled studies using representative patient groups and valid and standardized diagnostic instruments. So far, the majority of the studies have concerned axis I disorders; relatively little research has been performed on axis II personality disorders. More research on personality disorders, as well as on the relative contributions of the different (brain- and non-brain-related) factors to the relationship between epilepsy and psychiatric disorders, is recommended.

Two-year course of depressive and anxiety disorders: Results from the Netherlands Study of Depression and Anxiety (NESDA).

BACKGROUND Whether course trajectories of depressive and anxiety disorders are different, remains an important question for clinical practice and informs future psychiatric nosology. This longitudinal study compares depressive and anxiety disorders in terms of diagnostic and symptom course trajectories, and examines clinical prognostic factors. METHODS Data are from 1209 depressive and/or anxiety patients residing in primary and specialized care settings, participating in the Netherlands Study of Depression and Anxiety. Diagnostic and Life Chart Interviews provided 2-year course information. RESULTS Course was more favorable for pure depression (n=267, median episode duration = 6 months, 24.5% chronic) than for pure anxiety (n=487, median duration = 16 months, 41.9% chronic). Worst course was observed in the comorbid depression-anxiety group (n=455, median duration > 24 months, 56.8% chronic). Independent predictors of poor diagnostic and symptom trajectory outcomes were severity and duration of index episode, comorbid depression-anxiety, earlier onset age and older age. With only these factors a reasonable discriminative ability (C-statistic 0.72-0.77) was reached in predicting 2-year prognosis. LIMITATION Depression and anxiety cases concern prevalent - not incident - cases. This, however, reflects the actual patient population in primary and specialized care settings. CONCLUSIONS Their differential course trajectory justifies separate consideration of pure depression, pure anxiety and comorbid anxiety-depression in clinical practice and psychiatric nosology.

Meta-Analysis of Genome-Wide Association Data of Bipolar Disorder and Major Depressive Disorder

Meta-analysis of genome-wide association data of bipolar disorder and major depressive disorder

Prediction of outcome and early vs. late improvement in OCD patients treated with cognitive behaviour therapy and pharmacotherapy

In this study, follow‐up results of cognitive‐behaviour therapy and of a combination of cognitive‐behaviour therapy with a serotonergic antidepressant were determined. The study also examined factors that can predict this treatment effect, both in the long term and in the short term. In addition, it investigated whether differential prediction is possible for cognitive‐behaviour therapy vs. a combination of cognitive‐behaviour therapy with a serotenergic antidepressant. A total of 99 patients were included in the study. Treatment lasted 16 weeks, and a naturalistic follow‐up measurement was made 6 months later. Of the 70 patients who completed the treatment, follow‐up information was available for 61 subjects. Significant time effects were found on all outcome measures at both post‐treatment measurement and follow‐up. No differences in efficacy were found between the treatment conditions. Effectiveness at post‐treatment measurement appears to predict success at follow‐up. However, 17 of the 45 non‐responders at the post‐treatment measurement had become responders by the follow‐up. The severity of symptoms, motivation for treatment and the dimensional score on the PDQ‐R for cluster A personality disorder appear to predict treatment outcome. No predictors were found that related specifically to cognitive‐behaviour therapy or combined treatment. These results indicate that the effectiveness of cognitive‐behaviour therapy or a combination of cognitive‐behaviour therapy and fluvoxamine at the post‐treatment measurement is maintained at follow‐up. However, non‐response at post‐treatment does not always imply non‐response at follow‐up. Patients with more severe symptoms need a longer period of therapy to become responders. Although predictors for treatment success were found, no evidence was found to determine the choice of one of the treatment modalities.

Comorbidity of the anxiety disorders in a community-based older population in The Netherlands

Objective: The aim of the study was to investigate patterns of comorbidity among the anxiety disorders in a community‐based older population, and the relationship of these disorders with major depression, use of alcohol and benzodiazepines, cognitive impairment and chronic somatic illnesses.