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Differential susceptibility theory (DST) posits that individuals differ in their developmental plasticity: some children are highly responsive to both environmental adversity and support, while others are less affected. According to this theory, “plasticity” genes that confer risk for psychopathology in adverse environments may promote superior functioning in supportive environments. We tested DST using a broad measure of child genetic liability (based on birth parent psychopathology), adoptive home environmental variables (e.g., marital warmth, parenting stress, and internalizing symptoms), and measures of child externalizing problems (n = 337) and social competence (n = 330) in 54-month-old adopted children from the Early Growth and Development Study. This adoption design is useful for examining DST because children are placed at birth or shortly thereafter with nongenetically related adoptive parents, naturally disentangling heritable and postnatal environmental effects. We conducted a series of multivariable regression analyses that included Gene × Environment interaction terms and found little evidence of DST; rather, interactions varied depending on the environmental factor of interest, in both significance and shape. Our mixed findings suggest further investigation of DST is warranted before tailoring screening and intervention recommendations to children based on their genetic liability or “sensitivity.”
In research and clinical practice, familial risk for depression and anxiety is often constructed as a simple Yes/No dichotomous family history (FH) indicator. However, this measure may not fully capture the liability to these conditions. This study investigated whether a continuous familial loading score (FLS), incorporating family- and disorder-specific characteristics (e.g. family size, prevalence of depression/anxiety), (i) is associated with a polygenic risk score (PRS) for major depression and with clinical/psychosocial vulnerabilities and (ii) still captures variation in clinical/psychosocial vulnerabilities after information on FH has been taken into account.
Data came from 1425 participants with lifetime depression and/or anxiety from the Netherlands Study of Depression and Anxiety. The Family Tree Inventory was used to determine FLS/FH indicators for depression and/or anxiety.
Persons with higher FLS had higher PRS for major depression, more severe depression and anxiety symptoms, higher disease burden, younger age of onset, and more neuroticism, rumination, and childhood trauma. Among these variables, FH was not associated with PRS, severity of symptoms, and neuroticism. After regression out the effect of FH from the FLS, the resulting residualized measure of FLS was still associated with severity of symptoms of depression and anxiety, rumination, and childhood trauma.
Familial risk for depression and anxiety deserves clinical attention due to its associated genetic vulnerability and more unfavorable disease profile, and seems to be better captured by a continuous score that incorporates family- and disorder-specific characteristics than by a dichotomous FH measure.
Both attention-deficit/hyperactivity disorder (ADHD) and insomnia have been independently related to poorer quality of life (QoL), productivity loss, and increased health care use, although most previous studies did not take the many possible comorbidities into account. Moreover, ADHD and insomnia often co-occur. Symptoms of ADHD and insomnia together may have even stronger negative effects than they do separately. We investigated the combined effects of symptoms of ADHD and insomnia, in addition to their independent effects, on QoL, productivity, and health care use, thereby controlling for a wide range of possible comorbidities and confounders.
Data from the third wave of the Netherlands Mental Health Survey and Incidence Study-2 were used, involving N = 4618 from the general population. Both the inattention and the hyperactivity ADHD symptom dimensions were studied, assessed by the ASRS Screener.
Mental functioning and productivity were negatively associated with the co-occurrence of ADHD and insomnia symptoms, even after adjusting for comorbidity and confounders. The results show no indication of differences between inattention and hyperactivity. Poorer physical functioning and health care use were not directly influenced by the interaction between ADHD and insomnia.
People with both ADHD and sleep problems have increased risk for poorer mental functioning and productivity loss. These results underscore the importance of screening for sleep problems when ADHD symptoms are present, and vice versa, and to target both disorders during treatment.
Metabolites are small molecules involved in cellular metabolism where they act as reaction substrates or products. The term ‘metabolomics’ refers to the comprehensive study of these molecules. The concentrations of metabolites in biological tissues are under genetic control, but this is limited by environmental factors such as diet. In adult mono- and dizygotic twin pairs, we estimated the contribution of genetic and shared environmental influences on metabolite levels by structural equation modeling and tested whether the familial resemblance for metabolite levels is mainly explained by genetic or by environmental factors that are shared by family members. Metabolites were measured across three platforms: two based on proton nuclear magnetic resonance techniques and one employing mass spectrometry. These three platforms comprised 237 single metabolic traits of several chemical classes. For the three platforms, metabolites were assessed in 1407, 1037 and 1116 twin pairs, respectively. We carried out power calculations to establish what percentage of shared environmental variance could be detected given these sample sizes. Our study did not find evidence for a systematic contribution of shared environment, defined as the influence of growing up together in the same household, on metabolites assessed in adulthood. Significant heritability was observed for nearly all 237 metabolites; significant contribution of the shared environment was limited to 6 metabolites. The top quartile of the heritability distribution was populated by 5 of the 11 investigated chemical classes. In this quartile, metabolites of the class lipoprotein were significantly overrepresented, whereas metabolites of classes glycerophospholipids and glycerolipids were significantly underrepresented.
There are widespread concerns about the quality of mental health care for ethnic minority groups. This is supported mainly by studies from the U.S. and Great-Britain, raising doubts about the generalisability to (other) European countries. This study investigates ethnic differences in quality of care (QoC) for common mental disorders (CMD) in primary and outpatient mental health care in the Netherlands.
Data from electronic records of 89 primary care practices in 2007 (6,246 cases), and longitudinal data (2001 - 2005) from a nationwide psychiatric case register (17,270 cases). Quality of primary care indicators were ‘detection of CMD’, ‘adequate follow-up’, ‘adequate prescription of psychotropics’ and ‘referral to specialised mental health care’. Outpatient mental health care indicators were ‘waiting times’, ‘treatment intensity’, ‘early dropout’ and ‘early re-registration.
Compared with ethnic Dutch, quality of primary care was less for Turkish clients (CMD less likely to be detected) and Surinamese/Antillean clients (less than adequate prescription of psychotropics). Outpatient mental health treatment was less favourable for Moroccan and Turkish clients (longer waiting times and lower treatment intensity), but more favourable for Surinamese/Antillean clients (shorter waiting times and lower dropout).
The data do not provide sufficient support for a generalising statement that quality of CMD treatment is less favourable for ethnic minority clients. Though negative findings are not to be disregarded, positive findings - which may be related to the promotion of culturally sensitive care approaches in mainstream mental health services - deserve attention as well.
In the Netherlands, the Depression Initiative has been launched in 2006 as a nationwide attempt to implement the Multidisciplinary Guideline for Depression and to evaluate its cost effectiveness. Evaluation of a collaborative stepped care model in several health care settings is one of the objectives of the Depression Initiative. Currently a stepped collaborative care project is being evaluated in the primary care setting, evaluating stepped collaborative care for depressive disorder provided by the primary care practitioner, a nurse-care-manager, and a consultant psychiatrist, in a Randomised Controlled Trial. 150 Patients with depressive disorder are offered a treatment plan. They can choose from two options: Problem Solving Treatment with or without antidepressant treatment. The medication is prescribed by the PCP, PST and monitoring is provided by the care manager, and the psychiatrist can be consulted every 6 weeks in order to see if the intervention is sufficient to improve the symptoms of the patient. The PHQ is used for monitoring. A two step approach is aimed at; if the patient does not achieve remission after 18 weeks, the patient is referred to mental health care. This stepwise approach is supported by a training and supervision program and by a web-based tracking system in which the care-manager and the patient can monitor progress and consult the psychiatrist. This approach is compared with Care As Usual in the primary care setting. In the presentation, preliminary results will be presented.
About 13 percent of older individuals have symptoms of depression, and other researchers have speculated that vitamin D may be linked to depression. Underlying causes of vitamin D deficiency such as less sun exposure as a result of decreased outdoor activity, different housing or clothing habits and decreased vitamin intake may be secondary to depression, but depression may also be the consequence of poor vitamin D status. Moreover, poor vitamin D status causes an increase in serum parathyroid hormone levels. Overactive parathyroid glands are frequently accompanied by symptoms of depression that disappear after treatment of the condition. We recently measured blood levels of vitamin D and parathyroid hormone and assessed symptoms of depression among 1,282 community residents age 65 to 95 and found a strong decrease in vitamin D level and increase in parathyroid hormone level (Hoogendijk et al., Arch Gen Psychiat 2008;65(5):508-512). This finding may be important to patients because both low blood vitamin D levels and high parathyroid hormone levels can be treated with higher dietary intake of vitamin D or calcium and increased sunlight exposure. Moreover light treatment has been used successfully to treat seasonal affective disorder. Taking these two lines of studies together, sunlight may have an antidepressant effect via the eye-biological clock tract and via the skin-vitamin D-tract. Interestingly, the biological clock is located in the hypothalamus, where vitamin D receptor is most abundant.
Chronic depressions are difficult to treat. A new form of psychotherapy, CBASP, has been specifically developed for this subgroup of depressed patients by James McCullough (USA). In a large multisite randomized controlled trial, the combination of CBASP with antidepressant medication was considerably more effective than antidepressants alone (response rates of 73% versus 48% respectively). Therefore, CBASP is regarded as an evidence based therapy for chronic depression and mentioned in most depression treatment guidelines. Yet, the dissemination of this form of psychotherapy is still limited.
In the Netherlands, 25 therapists were trained by McCullough, and participate in a recently started (June 2007) randomized controlled trial, comparing CBASP with usual care in outpatient psychiatric clinics. The basic structure of the CBASP sessions is cognitive behaviorally oriented. Patients are learned to perform analyses of specific situations, and bring in and discuss a situational analysis form every session. As this approach alone often fails in chronic depressed patients, who are often emotionally detached and avoidant, other techniques are used to develop a therapeutic relationship, and to confront the patient with his/her behavior and opportunities to change. These techniques concern transference issues, and so-called disciplined personal involvement of the therapist.
This presentation will focus on the content of the CBASP therapy and on our experiences in learning and providing CBASP. Additionally, the study design of the randomized controlled trial will be presented.
CBASP is an interesting and promising treatment for chronically depressed patients.
Major depression is a highly recurrent and disabling disorder. At least 60% of first depressed individuals will have another episode. Knowledge of the predictors of recurrence is crucial in advising continuation and/or maintenance treatment.
Over the last 20-30 years a number of studies identified several sociodemographic-, psychosocial-, personality-, and clinical factors associated with the recurrence of major depression.
This presentation will give an overview of the most important predictors associated with recurrence of depression. Relevant articles were obtained through a search in Medline, Embase, and PsycINFO with the keywords recurrence, relapse, and major depression. This search covered the period from 1980 to 2007. Criteria to select the best studies will be presented.
The studies were further divided in general population studies, primary care and specialised mental health care studies.
The Netherlands Study of Depression and Anxiety (NESDA, www.nesda.nl) is an ongoing study to: 1) describe the long-term course and consequences of depressive and anxiety disorders, and 2) to examine the demographic, psychosocial, somatic, biological and genetic determinants of this course. This presentation describes NESDA's rationale, sampling frame and methods.
The design is an 8-year longitudinal cohort study following 2,850 participants aged 18 through 65 years. The sample consists of 1600 persons with a current (6 month recency) diagnosis of depression or anxiety disorder, 850 persons at risk (because of high symptomatology, family or life-time history), and 400 healthy controls. Recruitment takes place in the community, through 65 general practitioners (using a three-stage screening procedure), and through 17 mental health care institutions in order to include patients reflecting various settings and stages of psychopathology. The 4-hour baseline assessment includes questionnaires, interviews, a medical exam, a computer task and blood (including DNA and RNA) and saliva collections. Follow-up assessments are repeated after 1, 2, 4 and 8 years.
Over 2500 respondents with more than 2100 current diagnoses of depression or anxiety disorders, were recruited in November 2006 (mean age = 41 years, 67% female). Expected end date of recruitment is in February 2007.
NESDA is expected to provide more insight into (predictors of) the course of affective disorders. NESDA is open for collaboration (including data utilization) with other European research groups, which we hope to stimulate by a presentation of its design and methods.
Epidemiological studies have shown that anxiety disorders and depressive disorders frequently co-occur. Comorbidity studies revealed that estimations on comorbidity patterns of anxiety disorder and depressive disorders differs widely (30-80%). These differences may be due to different sampling-frames (community sample; primary care sample; secondary care sample). Our data were derived from the first wave of the Netherlands Study on Depression and Anxiety (NESDA), a 10-year longitudinal study on the long term prognosis of anxiety and depression. In our sample, 1285 subjects (52%) had a Major Depressive Disorder and/or an anxiety disorder (GAD; Social Phobia, PD with or without agoraphobia; agoraphobia alone) measured with the CIDI. These subjects were recruited from the general population (9%), in primary care (46%) and in specialized mental health care (44%). Of the 870 subjects with a MDD in the previous 6-months, 60% had an anxiety disorder (6-months) and 71% had an life-time anxiety disorder. Of the 937 subjects with a PD, GAD, Social Phobia or Agoraphobia in the previous 6-months, 56% had a MDD (6-months) and 70% had an life-time MDD. As expected comorbidity between anxiety disorders and MDD were significantly higher for subjects recruited in specialized mental health care settings (50%), then for subjects recruited in primary health-care facilities (34%) and for subject recruited from general population (27%)(p<.001). These preliminary findings suggested high levels of comorbidity between MDD and anxiety disorder. Furthermore, our findings demonstrated higher comorbidity patterns for subjects in specialized mental health care-settings.
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.
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.
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.
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.
Although depression with anxious distress appears to be a clinically relevant subtype of Major Depressive Disorder (MDD), whether it involves specific pathophysiology remains unclear. Inflammation has been implicated, but not comprehensively studied. We examined within a large MDD sample whether anxious distress and related anxiety features are associated with differential basal inflammation and innate cytokine production capacity.
Data are from 1078 MDD patients from the Netherlands study of depression and anxiety. Besides the DSM-5 anxious distress specifier, we studied various dimensional anxiety scales (e.g. Inventory of Depressive Symptomatology anxiety arousal subscale [IDS-AA], Beck Anxiety Inventory [BAI], Mood and Anxiety Symptoms Questionnaire Anxious Arousal scale [MASQ-AA]). Basal inflammatory markers included C-reactive protein, interleukin (IL)-6 and tumor-necrosis factor (TNF)-α. Innate production capacity was assessed by 13 lipopolysaccharide (LPS)-stimulated inflammatory markers. Basal and LPS-stimulated inflammation index scores were created.
Basal inflammation was not associated with anxious distress in MDD patients (anxious distress prevalence 54.3%), except for modest positive associations for IDS-AA and BAI scores. However, anxious distress was associated with higher LPS-stimulated levels (interferon-ɣ, IL-2, IL-6, monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, MIP-1β, matrix metalloproteinase-2, TNF-α, TNF-β, LPS-stimulated index). Oher anxiety indicators (number of specifier items and anxiety diagnoses, IDS-AA, BAI, MASQ-AA) were also associated with increased innate production capacity.
Within a large MDD sample, the anxious distress specifier was associated with increased innate cytokine production capacity but not with basal inflammation. Results from dimensional anxiety indicators largely confirm these results. These findings provide new insight into the pathophysiology of anxious depression.
Major depressive disorder (MDD) is often considered an episodic disorder. However, literature might underestimate the chronicity of MDD since results depend on follow-up duration and the extent to which psychiatric co-morbidity is taken into account.
To determine, whether MDD should be considered an episodic or chronic disorder.
To examine the 6 year course of MDD, incorporating data of multiple time points and taking common psychiatric comorbidities into account.
Data were from 903 patients with current MDD at baseline in the Netherlands study of depression and anxiety, with subsequent data from 2 year, 4 year and 6 year follow-up. Four course trajectories were created taking all information during follow-up into account classifying patients as (1) recovered, (2) recurrent without chronic episodes, (3) recurrent with chronic episodes or (4) consistently chronic. A chronic episode was defined as having symptoms consistently over 2 years.
The recovery rate of MDD was 58% at 2 year follow-up but looking at 6 year follow-up and taking into account co-morbid dysthymia, (hypo) mania and anxiety disorders reduced this recovery rate to 17%. Moreover, more than half of the patients experienced chronic episodes.
Longitudinal data of this psychiatric cohort study showed that full recovery is the exception rather than the rule. MDD follows a chronic course and, moreover, persons are prone to switch to other psychiatric disorders.
Valproic acid (VPA) is widely used in the treatment of epilepsy and bipolar disorder. It is largely bound to serum proteins (80–95%) in particular albumin, with a saturable binding capacity. Under conditions of hypoalbuminemia, protein binding of VPA will decrease and its pharmacologically-active free fraction will rise, even to toxic levels while measuring subtherapeutic VPA total blood levels .
We present an elderly bipolar patient with (sub)clinical total levels of VPA and a high free fraction of VPA due to hypoalbuminemia (14–24 g/L) leading to severe reversible cognitive impairment.
VPA and the free fraction in particular, was the most likely cause of the cognitive impairment . There was a time-correlation with increasing blood levels of total VPA (68 mg/L, reference 80–120 mg/L ), notably the free fraction (37.5 mg/L, reference 5–15 mg/L), and the intoxication.
For therapeutic drug monitoring in laboratories, generally, total VPA concentrations (free + protein-bound) are measured instead of free fractions, due to technical difficulties, a lack of established reference ranges  and (inter)national guidelines [5,6] not requiring it. This presentation and literature points out that it is clinically relevant to measure the free fraction [7,8], especially in patients with hypoalbuminemia [9–11] to prevent unnecessary side effects and toxicity.
We recommend measuring albumin during VPA use; particularly in patients with nephrotic syndrome, liver disease  or older adults [13–15]. Hypoalbuminemia demands a free fraction measurement.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Studying birth-cohort differences in depression incidence and their explanatory factors may provide insight into the aetiology of depression and could help to optimise prevention strategies to reduce the worldwide burden of depression.
Data were used from the Longitudinal Aging Study Amsterdam, a nationally representative study among community dwelling older adults in the Netherlands. Cohort differences in depression incidence over a 10-year-period (score ⩾16 on the Center for Epidemiologic Studies Depression scale) were tested using a cohort-sequential-longitudinal-design, comparing two identically measured cohorts of non-depressed 55–64-year-olds, born 10-years apart. Baseline measurements took place in 1992/93 (early cohort, n = 794), and 2002/03 (recent cohort, n = 771). As indicated by the dynamic equilibrium model of depression, potential explanatory factors were distinguished in risk and protective factors.
The incidence rates for depression in the early and recent cohort were 1.91 (95% confidence interval (CI) 1.59–2.27) and 1.60 (95% CI 1.31–1.94) per 100 person-years, respectively. A 29% risk reduction in depression incidence was observed in the recent cohort (HRcohort: 0.71, 95% CI 0.54–0.92, p = 0.011), as compared with the early cohort, even though average levels of risk factors such as chronic disease and functional limitations had increased. This reduction was primarily explained by increased levels of education, mastery and labour market participation.
These findings suggest that favourable developments of protective factors have counterbalanced unfavourable effects of risk factors on the incidence of depression, resulting in a net reduction of depression incidence among young-old adults. However, maintaining a good physical health must be a priority to further decrease depression rates.
Psychiatric patients are at increased risk to become victim of violence. It remains unknown whether subjects of the general population with mental disorders are at risk of victimisation as well. In addition, it remains unclear whether the risk of victimisation differs across specific disorders. This study aimed to determine whether a broad range of mood, anxiety and substance use disorders at baseline predict adult violent (physical and/or sexual) and psychological victimisation at 3-year follow-up, also after adjustment for childhood trauma. Furthermore, this study aimed to examine whether specific types of childhood trauma predict violent and psychological victimisation at follow-up, after adjustment for mental disorder. Finally, this study aimed to examine whether the co-occurrence of childhood trauma and any baseline mental disorder leads to an incrementally increased risk of future victimisation.
Data were derived from the first two waves of the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2): a psychiatric epidemiological cohort study among a nationally representative adult population. Mental disorders were assessed using the Composite International Diagnostic Interview version 3.0. Longitudinal associations between 12 mental disorders at baseline and violent and psychological victimisation at 3-year follow-up (n = 5303) were studied using logistic regression analyses, with adjustment for sociodemographic characteristics and childhood trauma. Furthermore, the moderating effect of childhood trauma on these associations was examined.
Associations with victimisation varied considerably across specific mental disorders. Only alcohol dependence predicted both violent and psychological victimisation after adjustment for sociodemographic characteristics and childhood trauma. Depression, panic disorder, social phobia, generalised anxiety disorder and alcohol dependence predicted subsequent psychological victimisation in the fully adjusted models. All types of childhood trauma independently predicted violent and psychological victimisation after adjustment for any mental disorder. The presence of any childhood trauma moderated the association between any anxiety disorder and psychological victimisation, whereas no interaction between mental disorder and childhood trauma on violent victimisation existed.
The current study shows that members of the general population with mental disorders are at increased risk of future victimisation. However, the associations with violent and psychological victimisation vary considerably across specific disorders. Clinicians should be aware of the increased risk of violent and psychological victimisation in individuals with these mental disorders – especially those with alcohol dependence – and individuals with a history of childhood trauma. Violence prevention programmes should be developed for people at risk. These programmes should not only address violent victimisation, but also psychological victimisation.