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Antidepressant medications (ADMs) are widely used and long-term use is increasing. Given this extensive use and recommendation of ADMs in guidelines, one would expect ADMs to be universally considered effective. Surprisingly, that is not the case; fierce debate on their benefits and harms continues. This editorial seeks to understand why the controversy continues and how consensus can be achieved.
‘Position’ paper. Critical analysis and synthesis of relevant literature.
Advocates point at ADMs impressive effect size (number needed to treat, NNT = 6–8) in acute phase treatment and continuation/maintenance ADM treatment prevention relapse/recurrence in acute phase ADM responders (NNT = 3–4). Critics point at the limited clinically significant surplus value of ADMs relative to placebo and argue that effectiveness is overstated. We identified multiple factors that fuel the controversy: certainty of evidence is low to moderate; modest efficacy on top of strong placebo effects allows critics to focus on small net efficacy and advocates on large gross efficacy; ADM withdrawal symptoms masquerade as relapse/recurrence; lack of association between ADM treatment and long-term outcome in observational databases. Similar problems affect psychological treatments as well, but less so. We recommend four approaches to resolve the controversy: (1) placebo-controlled trials with relevant long-term outcome assessments, (2) inventive analyses of observational databases, (3) patient cohort studies including effect moderators to improve personalized treatment, and (4) psychological treatments as universal first-line treatment step.
Given the public health significance of depression and increased long-term ADM usage, new approaches are needed to resolve the controversy.
The association between dietary patterns and CVD risk factors among non-Hispanic whites has not been fully studied. Data from 650 non-Hispanic white adults who participated in one of two clinical sub-studies (about 2 years after the baseline) of the Adventist Health Study-2 (AHS-2) were analysed. Four dietary patters were identified using a validated 204-item semi-quantitative FFQ completed at enrolment into AHS-2: vegans (8·3 %), lacto-ovo-vegetarians (44·3 %), pesco-vegetarians (10·6 %) and non-vegetarians (NV) (37·3 %). Dietary pattern-specific prevalence ratios (PR) of CVD risk factors were assessed adjusting for confounders with or without BMI as an additional covariable. The adjusted PR for hypertension, high total cholesterol and high LDL-cholesterol were lower in all three vegetarian groups. Among the lacto-ovo-vegetarians the PR were 0·57 (95 % CI 0·45, 0·73), 0·72 (95 % CI 0·59, 0·88) and 0·72 (95 % CI 0·58, 0·89), respectively, which remained significant after additionally adjusting for BMI. The vegans and the pesco-vegetarians had similar PR for hypertension at 0·46 (95 % CI 0·25, 0·83) and 0·62 (95 % CI 0·42, 0·91), respectively, but estimates were attenuated and marginally significant after adjustment for BMI. Compared with NV, the PR of obesity and abdominal adiposity, as well as other CVD risk factors, were significantly lower among the vegetarian groups. Similar results were found when limiting analyses to participants not being treated for CVD risk factors, with the vegans having the lowest mean BMI and waist circumference. Thus, compared with the diet of NV, vegetarian diets were associated with significantly lower levels of CVD risk factors among the non-Hispanic whites.
Research in depression has progressed rapidly over the past four decades. Yet depression rates are not subsiding and treatment success is not improving. We examine the extent to which the gap between science and practice is associated with the level of integration in how depression is considered in research and stakeholder-relevant documents.
We used a network-science perspective to analyze similar uses of depression relevant terms in the Google News corpus (approximately 1 billion words) and the Web of Science database (120 000 documents).
These analyses yielded consistent pictures of insular modules associated with: (1) patient/providers, (2) academics, and (3) industry. Within academia insular modules associated with psychology, general medical, and psychiatry/neuroscience/biology were also detected.
These analyses suggest that the domain of depression is fragmented, and that advancements of relevance to one stakeholder group (academics, industry, or patients) may not translate to the others. We consider potential causes and associated responses to this fragmentation that could help to unify and advance translation from research on depression to the clinic, largely involving harmonizing employed language, bridging conceptual domains, and increasing communication across stakeholder groups.
This paper is devoted to dimensional reductions via the norm-resolvent convergence. We derive explicit bounds on the resolvent difference as well as spectral asymptotics. The efficiency of our abstract tool is demonstrated by its application on seemingly different partial differential equation problems from various areas of mathematical physics; all are analysed in a unified manner, known results are recovered and new ones established.
Alongside impulsive suicide attempts, clinicians encounter highly premeditated suicidal acts, particularly in older adults. We have previously found that in contrast to the more impulsive suicide attempters’ inability to delay gratification, serious and highly planned suicide attempts were associated with greater willingness to wait for larger rewards. This study examined neural underpinnings of intertemporal preference in suicide attempters. We expected that impulsivity and suicide attempts, particularly poorly planned ones, would predict altered paralimbic subjective value representations. We also examined lateral prefrontal and paralimbic correlates of premeditation in suicidal behavior.
A total of 48 participants aged 46–90 years underwent extensive clinical and cognitive characterization and completed the delay discounting task in the scanner: 26 individuals with major depression (13 with and 13 without history of suicide attempts) and 22 healthy controls.
More impulsive individuals displayed greater activation in the precuneus/posterior cingulate cortex (PCC) to value difference favoring the delayed option. Suicide attempts, particularly better-planned ones, were associated with deactivation of the lateral prefrontal cortex (lPFC) in response to value difference favoring the immediate option. Findings were robust to medication exposure, depression severity and possible brain damage from suicide attempts, among other confounders. Finally, in suicide attempters longer reward delays were associated with diminished parahippocampal responses.
Impulsivity was associated with an altered paralimbic (precuneus/PCC) encoding of value difference during intertemporal choice. By contrast, better-planned suicidal acts were associated with altered lPFC representations of value difference. The study provides preliminary evidence of impaired decision processes in both impulsive and premeditated suicidal behavior.
Altered corticostriatothalamic encoding of reinforcement is a core feature of depression. Here we examine reinforcement learning in late-life depression in the theoretical framework of the vascular depression hypothesis. This hypothesis attributes the co-occurrence of late-life depression and poor executive control to prefrontal/cingulate disconnection by vascular lesions.
Our fMRI study compared 31 patients aged ⩾60 years with major depression to 16 controls. Using a computational model, we estimated neural and behavioral responses to reinforcement in an uncertain, changing environment (probabilistic reversal learning).
Poor executive control and depression each explained distinct variance in corticostriatothalamic response to unexpected rewards. Depression, but not poor executive control, predicted disrupted functional connectivity between the striatum and prefrontal cortex. White-matter hyperintensities predicted diminished corticostriatothalamic responses to reinforcement, but did not mediate effects of depression or executive control. In two independent samples, poor executive control predicted a failure to persist with rewarded actions, an effect distinct from depressive oversensitivity to punishment. The findings were unchanged in a subsample of participants with vascular disease. Results were robust to effects of confounders including psychiatric comorbidities, physical illness, depressive severity, and psychotropic exposure.
Contrary to the predictions of the vascular depression hypothesis, altered encoding of rewards in late-life depression is dissociable from impaired contingency learning associated with poor executive control. Functional connectivity and behavioral analyses point to a disruption of ascending mesostriatocortical reward signals in late-life depression and a failure of cortical contingency encoding in elderly with poor executive control.
Vegetarian dietary patterns have been reported to be associated with a number of favourable health outcomes in epidemiological studies, including the Adventist Health Study 2 (AHS-2). Such dietary patterns may vary and need further characterisation regarding foods consumed. The aims of the present study were to characterise and compare the food consumption patterns of several vegetarian and non-vegetarian diets. Dietary intake was measured using an FFQ among more than 89 000 members of the AHS-2 cohort. Vegetarian dietary patterns were defined a priori, based on the absence of certain animal foods in the diet. Foods were categorised into fifty-eight minor food groups comprising seventeen major food groups. The adjusted mean consumption of each food group for the vegetarian dietary patterns was compared with that for the non-vegetarian dietary pattern. Mean consumption was found to differ significantly across the dietary patterns for all food groups. Increased consumption of many plant foods including fruits, vegetables, avocados, non-fried potatoes, whole grains, legumes, soya foods, nuts and seeds was observed among vegetarians. Conversely, reduced consumption of meats, dairy products, eggs, refined grains, added fats, sweets, snack foods and non-water beverages was observed among vegetarians. Thus, although vegetarian dietary patterns in the AHS-2 have been defined based on the absence of animal foods in the diet, they differ greatly with respect to the consumption of many other food groups. These differences in food consumption patterns may be important in helping to explain the association of vegetarian diets with several important health outcomes.
Background: Depression is frequently characterized by patterns of inflexible, maladaptive, and ruminative thinking styles, which are thought to result from a combination of decreased attentional control, decreased executive functioning, and increased negative affect. Cognitive Control Training (CCT) uses computer-based behavioral exercises with the aim of strengthening cognitive and emotional functions. A previous study found that severely depressed participants who received CCT exhibited reduced negative affect and rumination as well as improved concentration. Aims: The present study aimed to extend this line of research by employing a more stringent control group and testing the efficacy of three sessions of CCT over a 2-week period in a community population with depressed mood. Method: Forty-eight participants with high Beck Depression Inventory (BDI-II) scores were randomized to CCT or a comparison condition (Peripheral Vision Training; PVT). Results: Significant large effect sizes favoring CCT over PVT were found on the BDI-II (d = 0.73, p < .05) indicating CCT was effective in reducing negative mood. Additionally, correlations showed significant relationships between CCT performance (indicating ability to focus attention on CCT) and state affect ratings. Conclusions: Our results suggest that CCT is effective in altering depressed mood, although it may be specific to select mood dimensions.
The greenhouse gas (GHG) emissions, expressed in carbon dioxide equivalents (CO2-eq), of different Austrian biogas systems were analyzed and evaluated using life-cycle assessment (LCA) as part of a national project. Six commercial biogas plants were investigated and the analysis included the complete process chain: viz., the production and collection of substrates, the fermentation of the substrates in the biogas plant, the upgrading of biogas to biomethane (if applicable) and the use of the biogas or biomethane for heat and electricity or as transportation fuel. Furthermore, the LCA included the GHG emissions of construction, operation and dismantling of the major components involved in the process chain, as well as the use of by-products (e.g. fermentation residues used as fertilizers). All of the biogas systems reduced GHG emissions (in CO2-eq) compared with fossil reference systems. The potential for GHG reduction of the individual biogas systems varied between 60% and 100%. Type of feedstock and its reference use, agricultural practices, coverage of storage tanks for fermentation residues, methane leakage at the combined heat and power plant unit and the proportion of energy used as heat were identified as key factors influencing the GHG emissions of anaerobic digestion processes.
Sleep loss produces abnormal increases in reward seeking but the mechanisms underlying this phenomenon are poorly understood. The present study examined the influence of one night of sleep deprivation on neural responses to a monetary reward task in a sample of late adolescents/young adults.
Using a within-subjects crossover design, 27 healthy, right-handed late adolescents/young adults (16 females, 11 males; mean age 23.1 years) underwent functional magnetic resonance imaging (fMRI) following a night of sleep deprivation and following a night of normal sleep. Participants' recent sleep history was monitored using actigraphy for 1 week prior to each sleep condition.
Following sleep deprivation, participants exhibited increased activity in the ventral striatum (VS) and reduced deactivation in the medial prefrontal cortex (mPFC) during the winning of monetary reward, relative to the same task following normal sleep conditions. Shorter total sleep time over the five nights before the sleep-deprived testing condition was associated with reduced deactivation in the mPFC during reward.
These findings support the hypothesis that sleep loss produces aberrant functioning in reward neural circuitry, increasing the salience of positively reinforcing stimuli. Aberrant reward functioning related to insufficient sleep may contribute to the development and maintenance of reward dysfunction-related disorders, such as compulsive gambling, eating, substance abuse and mood disorders.
Previous work studying vegetarians has often found that they have lower blood pressure (BP). Reasons may include their lower BMI and higher intake levels of fruit and vegetables. Here we seek to extend this evidence in a geographically diverse population containing vegans, lacto-ovo vegetarians and omnivores.
Data are analysed from a calibration sub-study of the Adventist Health Study-2 (AHS-2) cohort who attended clinics and provided validated FFQ. Criteria were established for vegan, lacto-ovo vegetarian, partial vegetarian and omnivorous dietary patterns.
Clinics were conducted at churches across the USA and Canada. Dietary data were gathered by mailed questionnaire.
Five hundred white subjects representing the AHS-2 cohort.
Covariate-adjusted regression analyses demonstrated that the vegan vegetarians had lower systolic and diastolic BP (mmHg) than omnivorous Adventists (β = −6·8, P < 0·05 and β = −6·9, P < 0·001). Findings for lacto-ovo vegetarians (β = −9·1, P < 0·001 and β = −5·8, P < 0·001) were similar. The vegetarians (mainly the vegans) were also less likely to be using antihypertensive medications. Defining hypertension as systolic BP > 139 mmHg or diastolic BP > 89 mmHg or use of antihypertensive medications, the odds ratio of hypertension compared with omnivores was 0·37 (95 % CI 0·19, 0·74), 0·57 (95 % CI 0·36, 0·92) and 0·92 (95 % CI 0·50, 1·70), respectively, for vegans, lacto-ovo vegetarians and partial vegetarians. Effects were reduced after adjustment for BMI.
We conclude from this relatively large study that vegetarians, especially vegans, with otherwise diverse characteristics but stable diets, do have lower systolic and diastolic BP and less hypertension than omnivores. This is only partly due to their lower body mass.
Converging evidence implicates basal ganglia alterations in impulsivity and suicidal behavior. For example, D2/D3 agonists and subthalamic nucleus stimulation in Parkinson's disease (PD) trigger impulse control disorders and possibly suicidal behavior. Furthermore, suicidal behavior has been associated with structural basal ganglia abnormalities. Finally, low-lethality, unplanned suicide attempts are associated with increased discounting of delayed rewards, a behavior dependent upon the striatum. Thus, we tested whether, in late-life depression, changes in the basal ganglia were associated with suicide attempts and with increased delay discounting.
Fifty-two persons aged ⩾60 years underwent extensive clinical and cognitive characterization: 33 with major depression [13 suicide attempters (SA), 20 non-suicidal depressed elderly] and 19 non-depressed controls. Participants had high-resolution T1-weighted magnetization prepared rapid acquisition gradient–echo (MPRAGE) magnetic resonance imaging (MRI) scans. Basal ganglia gray matter voxel counts were estimated using atlas-based segmentation, with a highly deformable automated algorithm. Discounting of delayed rewards was assessed using the Monetary Choice Questionnaire (MCQ) and delay aversion with the Cambridge Gamble Task (CGT).
SA had lower putamen but not caudate or pallidum gray matter voxel counts, compared to the control groups. This difference persisted after accounting for substance use disorders and possible brain injury from suicide attempts. SA with lower putamen gray matter voxel counts displayed higher delay discounting but not delay aversion. Secondary analyses revealed that SA had lower voxel counts in associative and ventral but not sensorimotor striatum.
Our findings, although limited by small sample size and the case–control design, suggest that striatal lesions could contribute to suicidal behavior by increasing impulsivity.
Background: Recent advances have been made in the application of cognitive training strategies as interventions for mental disorders. One novel approach, cognitive control training (CCT), uses computer-based exercises to chronically increase prefrontal cortex recruitment. Activation of prefrontal control mechanisms have specifically been identified with attenuation of emotional responses. However, it is unclear whether recruitment of prefrontal resources alone is operative in this regard, or whether prefrontal control is important only in the role of explicit emotion regulation. This study examined whether exposure to cognitive tasks before an emotional challenge attenuated the effects of the emotional challenge. Aims: We investigated whether a single training session could alter participants' reactivity to subsequent emotional stimuli on two computer-based tasks as well as affect ratings made during the study. We hypothesized that individuals performing the Cognitive Control (CC) task as compared to those performing the Peripheral Vision (PV) comparison task would (1) report reduced negative affect following the mood induction and the emotion task, and (2) exhibit reduced reactivity (defined by lower affective ratings) to negative stimuli during both the reactivity and recovery phases of the emotion task and (3) show a reduced bias towards threatening information. Method: Fifty-nine healthy participants were randomized to complete CC tasks or PV, underwent a negative mood induction, and then made valence and arousal ratings for IAPS images, and completed an assessment of attentional bias. Results: Results indicated that a single-session of CC did not consistently alter participants' responses to either task. However, performance on the CC tasks was correlated on subsequent ratings of emotional images. Conclusions: While overall these results do not support the idea that affective responding is altered by making healthy volunteers use their prefrontal cortex before the affective task, they are discussed in the context of study design issues and future research directions.
This study investigated pupillary and behavioral responses to an emotional word valence identification paradigm among 32 pre-/early pubertal and 34 mid-/late pubertal typically developing children and adolescents. Participants were asked to identify the valence of positive, negative, and neutral words while pupil dilation was assessed using an eyetracker. Mid-/late pubertal children showed greater peak pupillary reactivity to words presented during the emotional word identification task than pre-/early pubertal children, regardless of word valence. Mid-/late pubertal children also showed smaller sustained pupil dilation than pre-/early pubertal children after the word was no longer on screen. These findings were replicated controlling for participants' age. In addition, mid-/late pubertal children had faster reaction times to all words, and rated themselves as more emotional during their laboratory visit compared to pre-/early pubertal children. Greater recall of emotional words following the task was associated with mid-/late pubertal status, and greater recall of emotional words was also associated with higher peak pupil dilation. These results provide physiological, behavioral, and subjective evidence consistent with a model of puberty-specific changes in neurobehavioral systems underpinning emotional reactivity.
The Arvedi Endless Strip Production plant to be started
in Cremona, Italy, is presented. The design and plant
configuration of this facility will allow fully-continuous casting
and, for the first time in the world, endless rolling of highquality
strip in a wide range of steel grades.
During 2002–2003 increased numbers of notified salmonellosis due to S. enterica serovar Agona were observed in Germany. In order to understand the recent spread of this serovar and to trace the route of infection to its source, a new phage-typing scheme and pulsed field gel electrophoresis (PFGE) were used to analyse these isolates. By using 14 bacteriophages, 52 phage types were distinguished among the S. Agona strains. PFGE also differentiated 52 different patterns. A combination of both methods generated 94 clonal types among 165 S. Agona strains originating from Germany and other countries including the United States, United Arab Emirates, Turkey, India, Austria and Finland, indicating a great biological diversity within this serovar. However, 36 recent S. Agona isolates from infantile gastroenteritis in Germany, from an untreated batch of aniseed imported from Turkey and from fennel-aniseed-caraway infusion (packed in tea bags) revealed clonal identity indicating their epidemiological relatedness as a new source of infection. It is suggested that strains of S. Agona will continue to be of public health concern, and that phage typing together with PFGE typing should be applied as reliable and rapid tools for epidemiological subtyping and future monitoring.
Patterns of brain activation associated with covert
performance of the Stroop Color–Word task were studied
in young, healthy, adult volunteers using blood oxygen
level dependent (BOLD) functional magnetic resonance imaging
(fMRI). Comparisons of the incongruous Stroop condition
were made with both color naming and word reading baselines.
Areas of the left and right anterior cingulate, the right
precuneus, and the left pars opercularis displayed larger
BOLD signal responses during the incongruous Stroop condition
than during baseline conditions. Activation of BOLD signals
in these areas was highly repeatable. In a second experiment,
pupil diameter was used to assess cognitive load in 7 individuals
studied during overt and covert performance of both Stroop
and color naming conditions. Cognitive load was similar
in overt and covert response conditions. Results from the
BOLD study indicate that brain regions participating in
selective visual attention and in the selection of motor
programs involved in speech were activated more by the
Stroop task than by the baseline tasks. The neural substrate
involved in the resolution of the perceptual and motor
conflicts elicited by the Stroop Color–Word task
does not appear to be a single brain region. Rather, a
network of brain regions is implicated, with separate regions
within this system supporting distinct functions. (JINS,
1999, 5, 308–319.)
This paper analyses the influence of the sapphire substrate on stress in GaN epilayers in the temperature range between 4K and 600K. Removal of the substrate by a laser assisted liftoff technique allows, for the first time, to distinguish between stress and other material specific temperature dependencies. In contrast to the prevailing assumption in the literature, that the difference in the thermal expansion coefficients is the main cause for stress it is found that the substrate has a rather small influence in the examined temperature range. The measured temperature dependence of stress is in contradiction to the published values for the thermal expansion coefficients for sapphire and GaN.
We report on growth of GaN on Germanium as an alternative substrate material. The GaN films were deposited on Ge(001) substrates by plasma-assisted molecular beam epitaxy. Atomic force microscopy, x-ray diffraction, photoluminescence, and Raman spectroscopy were used to characterize the structural and optical properties of the films. We observed that the Ga/N ratio plays a crucial role in determining the phase purity and crystal quality. Under N-rich conditions the films were phase-mixed, containing cubic and hexagonal GaN, while in the Ga-rich regime they were purily hexagonal. The latter samples show bandedge luminescence with linewidths as small as 31 meV at low temperatures.
We present results of high-pressure Raman-scattering experiments on bulk GaN and GaN grown on GaAs. We determined the Grüneisen parameters of both the cubic TO and LO phonon modes and the hexagonal A1, E1 and E2 modes. Our measurements reveal that the Grüneisen parameters for the GaAs substrate are about 30% smaller than those of bulk GaAs. This is a consequence of the lower compressibility of GaN compared to GaAs, which results in a pressure-induced biaxial strain on the substrate. From the pressure behavior of the GaAs modes and by comparing with our results for bulk GaN we obtained information about the biaxial strain in the GaN epitaxial layer.