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Dietary interventions did not prevent depression onset nor reduced depressive symptoms in a large multi-center randomized controlled depression prevention study (MooDFOOD) involving overweight adults with subsyndromal depressive symptoms. We conducted follow-up analyses to investigate whether dietary interventions differ in their effects on depressive symptom profiles (mood/cognition; somatic; atypical, energy-related).
Baseline, 3-, 6-, and 12-month follow-up data from MooDFOOD were used (n = 933). Participants received (1) placebo supplements, (2) food-related behavioral activation (F-BA) therapy with placebo supplements, (3) multi-nutrient supplements (omega-3 fatty acids and a multi-vitamin), or (4) F-BA therapy with multi-nutrient supplements. Depressive symptom profiles were based on the Inventory of Depressive Symptomatology.
F-BA therapy was significantly associated with decreased severity of the somatic (B = −0.03, p = 0.014, d = −0.10) and energy-related (B = −0.08, p = 0.001, d = −0.13), but not with the mood/cognition symptom profile, whereas multi-nutrient supplementation was significantly associated with increased severity of the mood/cognition (B = 0.05, p = 0.022, d = 0.09) and the energy-related (B = 0.07, p = 0.002, d = 0.12) but not with the somatic symptom profile.
Differentiating depressive symptom profiles indicated that food-related behavioral interventions are most beneficial to alleviate somatic symptoms and symptoms of the atypical, energy-related profile linked to an immuno-metabolic form of depression, although effect sizes were small. Multi-nutrient supplements are not indicated to reduce depressive symptom profiles. These findings show that attention to clinical heterogeneity in depression is of importance when studying dietary interventions.
With the increasing availability of large amounts of data in the livestock domain, we face the challenge to store, combine and analyse these data efficiently. With this study, we explored the use of a data lake for storing and analysing data to improve scalability and interoperability. Data originated from a 2-day animal experiment in which the gait score of approximately 200 turkeys was determined through visual inspection by an expert. Additionally, inertial measurement units (IMUs), a 3D-video camera and a force plate (FP) were installed to explore the effectiveness of these sensors in automating the visual gait scoring. We deployed a data lake using the IMU and FP data of a single day of that animal experiment. This encompasses data from 84 turkeys for which we preprocessed by performing an ‘extract, transform and load’ (ETL-) procedure. To test scalability of the ETL-procedure, we simulated increasing volumes of the available data from this animal experiment and computed the ‘wall time’ (elapsed real time) for converting FP data into comma-separated files and storing these files. With a simulated data set of 30 000 turkeys, the wall time reduced from 1 h to less than 15 min, when 12 cores were used compared to 1 core. This demonstrated the ETL-procedure to be scalable. Subsequently, a machine learning (ML) pipeline was developed to test the potential of a data lake to automatically distinguish between two classses, that is, very bad gait scores v. other scores. In conclusion, we have set up a dedicated customized data lake, loaded data and developed a prediction model via the creation of an ML pipeline. A data lake appears to be a useful tool to face the challenge of storing, combining and analysing increasing volumes of data of varying nature in an effective manner.
In middle-aged and older patients in whom antidepressant use increased in last decades, patterns of use might be of concern The objective of this study was to investigate the patterns of prevalence, incidence and duration of antidepressant use in an ageing population.
All participants (aged > 45 years) from the population-based Rotterdam Study were followed from January 1st 1991 until death, loss to follow-up, or end of the study period (December 31st 2011). Antidepressant drug dispensing, based on pharmacy records, were subdivided into Tricyclic Antidepressants (TCAs), Selective Serotonin Reuptake Inhibitors (SSRIs) and other antidepressants. One-year prevalence, 5-year incidence and duration of antidepressant use were calculated.
Yearly prevalence of antidepressant use increased from 3.9% in 1991 to 8.3% of the population in 2011. The increase in SSRI use was 5.8-fold, whereas use of other antidepressants doubled and TCA use remained stable over time. Incidence of all antidepressants decreased from 23.9 to 14.2 per 1000 person-years between 1992 and 2011. The duration of a first treatment episode increased over time.
Despite the prevalence of antidepressant use increased over time, incidence did not, which is most likely explained by a longer treatment duration and recurrent episodes.
Suicide remains the leading cause of premature death in patients with psychotic disorders. The lifetime suicide risk for schizophrenia is approximately 10%.
This study aims to compare the suicide risk over the past decade following recent onset psychosis to findings from the eighties and nineties in the same catchment area and to identify predictors of suicide in the context of the Psychosis Recent Onset Groningen – Survey (PROGR-S).
A medical file search was carried out to determine the current status of all patients admitted between 2000 and 2009. The suicide rate was compared with a study executed in 1973-1988 in the same catchment area. Predictors of suicide were investigated using Cox regression.
The status of 424 of the 614 patients was known in July 2014. Suicide occurred in 2.4% of the patients with psychotic disorders (n=10; mean follow-up 5.6 years); 6 out of 10 suicides took place within two years. Within two decades, the suicide rate dropped from 11% (follow-up 15 years, 8.5% after 5 years) to 2.4%. The Standardized Mortality Rate (SMR) of suicides compared with the general population was 41.6. A higher age was the only significant predictor for suicide. Neuroticism, living situation, disorganized and negative symptoms, and passive coping style showed a trend for significance. A significant reduction in the suicide rate was found for people with psychosis over the past decades.
A considerable drop in suicide rate was found. Given the high SMR, suicide research should have the highest priority.
Studies in the general population show cannabis use has a beneficial effect on metabolic disorders. Given the increased cardiometabolic risk in patients with psychotic disorders, as well as their prevalent use of cannabis, we aim to investigate whether such effects are also evident in these patients.
3176 patients with chronic psychotic disorders from mental health institutions in the Netherlands were included in the study. With multivariate regression analyses we examined the effects of cannabis use on metabolic risk factors; BMI, waist circumference, blood pressure (BP), cholesterol, HDL-C, LDL-C, triglycerides, glucose and HbA1c. Age, sex, smoking, alcohol use and antipsychotic drugs were included as confounders. Next, we examined change in metabolic risk factors after one-year follow up for cannabis users, non-users, discontinuers and starters.
We found a significant negative association between cannabis use and BMI (p=0.003), waist circumference (p>0.001), diastolic BP (p=0.015) and HbA1c (0.004). One year later, patients who had discontinued their cannabis use had a greater increase of BMI (p=0.002) and waist circumference (p=0.011) than other patients. They also had a greater increase of diastolic BP than non-users (p=0.036) or starters (p=0.004).
Discontinuation of cannabis use increased metabolic risk. To stop cannabis use is often an important treatment goal, because it reduces psychotic symptoms. However, physicians should be aware of the increased metabolic risk in patients who discontinue the use of cannabis. Extra attention should be paid to monitoring and treatment of metabolic parameters in these patients to prevent cardiovascular diseases and premature cardiovascular mortality.
Multidisciplinary guidelines in adolescent mental health care are based on RCTs, while treatment efficacy can be different from effectiveness seen in ‘the real world’. Studies in the real world conducted so far suggest that treatment has a negligible effect on follow-up symptomatology. However, these studies did not incorporate the pre-treatment trajectory of symptoms nor investigated a dose-response relationship.
To test whether future treatment users and non-users differed in emotional and behavioural problem scores, whether specialist mental health treatment (SMHT) was effective in reducing problem levels while controlling for pre-treatment trajectory, and to seek evidence of a dose-response relationship.
Six-year follow up data were used from the Tracking Adolescents’ Individual Lives Survey (TRAILS). We identified adolescents with a clinical level of problem behaviour on the Child Behaviour Checklist or Youth Self Report and first SMHT between the ages 13 and 16. Adolescents with a clinical level of problem behaviour but without SMHT use served as control group. A psychiatric case register provided data on number of treatment contacts. Using regression analysis, we predicted the effect of treatment on post-treatment problem scores.
Treated adolescents more often had a (severe) diagnosis than untreated adolescents. Pre-treatment trajectories barely differed between treated and untreated adolescents. Treatment predicted an increase in follow-up problem scores, regardless of the number of sessions.
The quasi-experimental design calls for modest conclusions. We might however need to take a closer look at real-world service delivery, and invest in developing treatments that can achieve sustainable benefits.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Watching videotaped personal compulsions together with a therapist might enhance the effect of cognitive–behavioural therapy in obsessive–compulsive disorder (OCD) but little is known about how patients experience this.
To performed a qualitative study that describes how watching these videos influences motivation for treatment and whether patients report any adverse events.
In this qualitative study, data were gathered in semi-structured interviews with 24 patients with OCD. The transcripts were coded by two researchers. They used a combination of open and thematic coding and discrepancies in coding were discussed.
The experience of watching videos with personal compulsions helped patients to realise that these compulsions are aberrant and irrational. Patients report increased motivation to resist their OCD and to adhere to therapy. No adverse events were reported.
Videos with personal compulsions create more awareness in patients with OCD that compulsions are irrational, leading to enhanced motivation for treatment.
Individuals with autism spectrum disorder (ASD) appear to be at increased risk of non-affective psychotic disorder (NAPD) and bipolar disorder (BD). However, most previous studies examined the co-occurrence of ASD and NAPD or BD, ignoring possible diagnostic bias and selection bias. We used longitudinal data from Dutch psychiatric case registers to assess the risk of NAPD or BD among individuals with ASD, and compared the results to those obtained for the Dutch population in earlier studies.
Individuals with ASD (n = 17 234) were followed up between 16 and 35 years of age. Kaplan–Meier estimates were used to calculate the risk of NAPD or BD. We conducted separate analyses to reduce possible bias, including an analysis among individuals diagnosed with ASD before age 16 years (n = 8337).
Of the individuals with ASD, 23.50% (95% confidence interval 21.87–25.22) were diagnosed with NAPD and 3.79% (3.06–4.69) with BD before age 35 years. The corresponding figures for the general population were 0.91% (0.63–1.28) and 0.13% (0.08–0.20). Risk estimates were substantially lower, but still higher than general population estimates, when we restricted our analyses to individuals diagnosed with ASD before age 16, with 1.87% (1.33–2.61) being diagnosed with NAPD and 0.57% (0.21–1.53) with BD before age 25 years. The corresponding figures for the general population were 0.63% (0.44–0.86) and 0.08% (0.05–0.12).
Individuals with ASD are at increased risk of NAPD or BD. This is likely not the result of diagnostic or selection bias.
The most popular beef breed in South Africa is the Bonsmara, a locally developed composite breed adapted to sub-tropical conditions. The establishment of a genomic reference population is currently ongoing for the application of genomic selection. To date, 583 Bonsmara cattle (388 bulls and 195 cows) have been genotyped with the GeneSeek® Genomic Profiler Bovine HD™ Chip (GGP-HD) 80 K chip, and the population structure of the reference population was studied. The average minor allele frequency for the Bonsmara was 0.280 across 56 248 autosomal single-nucleotide polymorphisms (SNPs), whereas the observed and expected heterozygosity values were 0.361 and 0.365, respectively. After pruning the data set for SNPs in linkage disequilibrium, 19 119 SNPs were retained, averaging 659 SNPs per autosomal chromosome. This generated an average SNP density of 1 SNP per 90 kb. Structure analysis revealed a non-homogenous population with a high level of genetic admixture, which may negatively influence genomic breeding value prediction accuracy. Genotyping of a further 990 Bonsmara cattle are pending, using the GeneSeek® GGP-HD 150 K chip. As more animals will be added to the reference population, the profile of the reference population are expected to change in such a way to ensure improved genomic estimated breeding value accuracies.
Timely recognition and treatment of mental disorders with an onset in childhood and adolescence is paramount, as these are characterized by greater severity and longer persistence than disorders with an onset in adulthood. Studies examining time-to-treatment, also referred to as treatment delay, duration of untreated illness or latency to treatment, and defined as the time between disorder onset and initial treatment contact, are sparse and all based on adult samples. The aim of this study was to describe time-to-treatment and its correlates for any health care professional (any care) and secondary mental health care (secondary care), for a broad range of mental disorders, in adolescents.
Data from the Dutch community-based cohort study TRacking Adolescents’ Individual Lives Survey (TRAILS; N = 2230) were used. The Composite International Diagnostic Interview (CIDI) was administered to assess DSM-IV disorders, the age of onset, and the age of initial treatment contact with any health care professional in 1584 adolescents of 18–20 years old. In total 43% of the adolescents (n = 675) were diagnosed with a lifetime DSM-IV disorder. The age of initial treatment contact with secondary care was based on administrative records from 321 adolescents without a disorder onset before the age of 10. Descriptive statistics, cumulative lifetime probability plots, and Cox regression analyses were used analyze time-to-treatment.
The proportion of adolescents who reported lifetime treatment contact with any care varied from 15% for alcohol dependence to 82% for dysthymia. Regarding secondary care, proportions of lifetime treatment contact were lower for mood disorders and higher for substance dependence. Time-to-treatment for any care varied considerably between and within diagnostic classes. The probability of lifetime treatment contact for mood disorders was above 90%, whereas for other mental disorders this was substantially lower. An earlier age of onset predicted a longer, and the presence of a co-morbid mood disorder predicted a shorter time-to-treatment in general. Disorder severity predicted a shorter time-to-treatment for any care, but not for secondary care. Time-to-treatment for secondary care was shorter for adolescents from low and middle socioeconomic background than for adolescents from a high socioeconomic background.
Although the time-to-treatment was shorter for adolescents than for adults, it was still substantial, and the overall patterns were remarkably similar to those found in adults. Efforts to reduce time-to-treatment should therefore be aimed at children and adolescents. Future research should address mechanisms underlying time-to-treatment and its consequences for early-onset disorders in particular.
Tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) may be associated with lower heart rate variability (HRV), a condition associated with increased mortality risk. We aimed to investigate the association between TCAs, SSRIs and HRV in a population-based study.
In the prospective Rotterdam Study cohort, up to five electrocardiograms (ECGs) per participant were recorded (1991–2012). Two HRV variables were studied based on 10-s ECG recordings: standard deviation of normal-to-normal RR intervals (SDNN) and root mean square of successive RR interval differences (RMSSD). We compared the HRV on ECGs recorded during use of antidepressants with the HRV on ECGs recorded during non-use of any antidepressant. Additionally, we analysed the change in HRV on consecutive ECGs. Those who started or stopped using antidepressants before the second ECG were compared with non-users on two ECGs.
We included 23 647 ECGs from 11 729 participants (59% women, mean age 64.6 years at baseline). Compared to ECGs recorded during non-use of antidepressants (n = 22 971), SDNN and RMSSD were lower in ECGs recorded during use of TCAs (n = 296) and SSRIs (n = 380). Participants who started using TCAs before the second ECG had a decrease in HRV and those who stopped had an increase in HRV compared to consistent non-users (p < 0.001). Starting or stopping SSRIs was not associated with HRV changes.
TCAs were associated with a lower HRV in all analyses, indicating a real drug effect. For SSRIs the results are mixed, indicating a weaker association, possibly due to other factors.
We investigated the course of decline in multiple cognitive domains in non-demented subjects from a memory clinic setting, and compared pattern, onset and magnitude of decline between subjects who progressed to Alzheimer's disease (AD) dementia at follow-up and subjects who did not progress.
In this retrospective cohort study 819 consecutive non-demented patients who visited the memory clinics in Maastricht or Amsterdam between 1987 and 2010 were followed until they became demented or for a maximum of 10 years (range 0.5–10 years). Differences in trajectories of episodic memory, executive functioning, verbal fluency, and information processing speed/attention between converters to AD dementia and subjects remaining non-demented were compared by means of random effects modelling.
The cognitive performance of converters and non-converters could already be differentiated seven (episodic memory) to three (verbal fluency and executive functioning) years prior to dementia diagnosis. Converters declined in these three domains, while non-converters remained stable on episodic memory and executive functioning and showed modest decline in verbal fluency. There was no evidence of decline in information processing speed/attention in either group.
Differences in cognitive performance between converters to AD dementia and subjects remaining non-demented could be established 7 years prior to diagnosis for episodic memory, with verbal fluency and executive functioning following several years later. Therefore, in addition to early episodic memory decline, decline in executive functions may also flag incident AD dementia. By contrast, change in information processing speed/attention seems less informative.
Few studies have investigated the efficacy of repetitive transcranial magnetic stimulation (rTMS) treatment for negative symptoms of schizophrenia, reporting inconsistent results. We aimed to investigate whether 10 Hz stimulation of the bilateral dorsolateral prefrontal cortex during 3 weeks enhances treatment effects.
A multicenter double-blind randomized controlled trial was performed in 32 patients with schizophrenia or schizo-affective disorder, and moderate to severe negative symptoms [Positive and Negative Syndrome Scale (PANSS) negative subscale ⩾15]. Patients were randomized to a 3-week course of active or sham rTMS. Primary outcome was severity of negative symptoms as measured with the Scale for the Assessment of Negative Symptoms (SANS) and the PANSS negative symptom score. Secondary outcome measures included cognition, insight, quality of life and mood. Subjects were followed up at 4 weeks and at 3 months. For analysis of the data a mixed-effects linear model was used.
A significant improvement of the SANS in the active group compared with sham up to 3 months follow-up (p = 0.03) was found. The PANSS negative symptom scores did not show a significant change (p = 0.19). Of the cognitive tests, only one showed a significant improvement after rTMS as compared with sham. Finally, a significant change of insight was found with better scores in the treatment group.
Bilateral 10 Hz prefrontal rTMS reduced negative symptoms, as measured with the SANS. More studies are needed to investigate optimal parameters for rTMS, the cognitive effects and the neural basis.
Anxiety, apathy and depression are common in subjects with mild cognitive impairment (MCI) and may herald Alzheimer's disease (AD). We investigated whether these symptoms correlated with cerebrospinal fluid (CSF) markers for AD in subjects with MCI.
Subjects with MCI (n=268) were selected from the ‘Development of screening guidelines and criteria for pre-dementia Alzheimer's disease’ (DESCRIPA) and Alzheimer's Disease Neuroimaging Initiative (ADNI) studies. We measured amyloid β(1-42) protein (Aβ42) and total tau (t-tau) in CSF. Neuropsychiatric symptoms were measured with the Neuropsychiatric Inventory.
Depressive symptoms were reported by 55 subjects (21%), anxiety by 35 subjects (13%) and apathy by 49 subjects (18%). The presence of anxiety was associated with abnormal CSF Aβ42 [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.6–3.3] and t-tau (OR 2.6, 95% CI 1.9–3.6) concentrations and with the combination of abnormal concentrations of both Aβ42 and t-tau (OR 3.1, 95% CI 2.0–4.7). The presence of agitation and irritability was associated with abnormal concentrations of Aβ42 (agitation: OR 1.6, 95% CI 1.1–2.3; irritability: OR 2.2, 95% CI 1.5–3.3). Symptoms of depression and apathy were not related to any of the CSF markers.
In subjects with MCI, symptoms of anxiety, agitation and irritability may reflect underlying AD pathology, whereas symptoms of depression and apathy do not.
Ice desorption affects the evolution of the gas-phase chemistry during the protostellar
stage, and also determines the ice composition of comets forming in circumstellar disks.
From observations, most volatile species, including CO2, are found in
H2O-dominated ices. In this study, the desorption of CO2 mixed in
H2O ice and the impact of ice thickness, mixture ratio and heating rate are
experimentally determined. The results are used to parametrize an extended three-phase
model (gas, ice surface and ice mantle) which describes ice mixture desorption using rate
equations and a minimum number of free parameters. The model can be used to predict the
evolution in thickness and concentration of volatile-rich H2O ice during infall
of icy grains around protostars.
In shock, organ perfusion is of vital importance because organ oxygenation is at risk. NO, the main endothelial-derived vasodilator, is crucial for organ perfusion and coronary patency. The availability of NO might depend on the balance between a substrate (arginine) and an inhibitor (asymmetric dimethylarginine; ADMA) of NO synthase. Therefore, we investigated the relationship of arginine, ADMA and their ratio with circulatory markers, disease severity, organ failure and mortality in shock patients. In forty-four patients with shock (cardiogenic n 17, septic n 27), we prospectively measured plasma arginine and ADMA at intensive care unit admission, Acute Physiology and Chronic Health Evaluation (APACHE) II-(predicted mortality) and Sequential Organ Failure Assessment (SOFA) score, and circulatory markers to investigate their relationship. Arginine concentration was decreased (34·6 (sd 17·9) μmol/l) while ADMA concentration was within the normal range (0·46 (sd 0·18) μmol/l), resulting in a decrease in the arginine:ADMA ratio. The ratio correlated with several circulatory markers (cardiac index, disseminated intravascular coagulation, bicarbonate, lactate and pH), APACHE II and SOFA score, creatine kinase and glucose. The arginine:ADMA ratio showed an association (OR 0·976, 95 % CI 0·963, 0·997, P = 0·025) and a diagnostic accuracy (area under the curve 0·721, 95 % CI 0·560, 0·882, P = 0·016) for hospital mortality, whereas the arginine or ADMA concentration alone or APACHE II-predicted mortality failed to do so. In conclusion, in shock patients, the imbalance of arginine and ADMA is related to circulatory failure, organ failure and disease severity, and predicts mortality. We propose a pathophysiological mechanism in shock: the imbalance of arginine and ADMA contributes to endothelial and cardiac dysfunction resulting in poor organ perfusion and organ failure, thereby increasing the risk of death.
Loneliness has a significant influence on both physical and mental health. Few studies have investigated the possible associations of loneliness with mortality risk, impact on men and women and whether this impact concerns the situation of being alone (social isolation), experiencing loneliness (feeling lonely) or both. The current study investigated whether social isolation and feelings of loneliness in older men and women were associated with increased mortality risk, controlling for depression and other potentially confounding factors.
In our prospective cohort study of 4004 older persons aged 65–84 years with a 10-year follow-up of mortality data a Cox proportional hazard regression analysis was used to test whether social isolation factors and feelings of loneliness predicted an increased risk of mortality, controlling for psychiatric disorders and medical conditions, cognitive functioning, functional status and sociodemographic factors.
At 10 years follow-up, significantly more men than women with feelings of loneliness at baseline had died. After adjustment for explanatory variables including social isolation, the mortality hazard ratio for feelings of loneliness was 1.30 [95% confidence interval (CI) 1.04–1.63] in men and 1.04 (95% CI 0.90–1.24) in women. No higher risk of mortality was found for social isolation.
Feelings of loneliness rather than social isolation factors were found to be a major risk factor for increasing mortality in older men. Developing a better understanding of the nature of this association may help us to improve quality of life and longevity, especially in older men.