Driving Performance of Depressed Patients who are Untreated or Receive Long-Term Antidepressant (SSRI/SNRI) Treatment.

Introduction Depression is a mental disorder likely to affect everyday functions. The present study aimed to assess actual driving performance of depressed patients who were without specific antidepressant treatment or received long-term antidepressant treatment. Methods A standardized on-the-road driving test was used to assess standard deviation of lateral position (SDLP) in 3 patient groups receiving either no antidepressant treatment (with or without benzodiazepine medication) or treatment with selective serotonin/noradrenalin reuptake inhibitors for a period of 6-52 weeks. Severity of depression was assessed using Beck's Depression Inventory and the Hamilton Depression Rating Scale. The performance of patient groups was compared to healthy controls. Results The mean SDLP of untreated and treated patients was significantly higher than that of healthy controls. Driving impairment in the long-term treated group was significantly less than in the untreated groups. SDLP was positively correlated to severity of depression across all groups. Discussion It is concluded that symptoms of depression are a major cause of driving impairment. Reductions in severity of depression through antidepressant treatment reduce severity of driving impairment.

The impact of area-based initiatives on physical activity trends in deprived areas; a quasi-experimental evaluation of the Dutch District Approach.

BACKGROUND: Numerous area-based initiatives (ABIs) have been implemented in deprived neighbourhoods across Europe. These large-scale initiatives aim to tackle the socio-economic and environmental problems in these areas that might influence physical activity (PA). There is little robust evidence of their impact on PA. This study aimed to assess the impact of a Dutch ABI called the District Approach on trends in leisure-time PA in deprived districts. METHODS: Repeated cross-sectional data on 48401 adults across the Netherlands were obtained from the Integrated Survey on Household Living Conditions (POLS) 2004-2011. 1517 of these adults resided in deprived target districts and 46884 adults resided elsewhere in the Netherlands. In a quasi-experimental interrupted time-series design, multilevel logistic regression analyses were performed to assess trends in leisure-time walking, cycling, and sports before and during the intervention. Trends in deprived target districts were compared with trends in various control groups. The role of the intensity of environmental interventions was also assessed. RESULTS: Deprived target districts showed a significantly positive change in walking trend between the pre-intervention and intervention period. The trend change in the deprived target districts was significantly larger compared to the rest of the Netherlands, but not compared to other deprived districts. For cycling and sports, neither deprived districts nor control districts showed a significant trend change. For all leisure-time PA outcomes, trend changes were not related to the intensity of environmental interventions in the deprived target districts. CONCLUSION: Some evidence was found to suggest that ABIs like the District Approach have a positive impact on leisure-time PA in deprived districts, regardless of the intensity of environmental interventions.

[Home care in deprived districts: what is the role of material wealth?]. / Thuiszorg in aandachtswijken: wat is de rol van materiële welvaart?

OBJECTIVE: To examine if there is a higher uptake of home care among residents of deprived districts and to determine if this can be attributed to the lower levels of income and wealth of these residents. DESIGN: Retrospective, descriptive study. METHOD: The study focused on residents aged 50 and above. We obtained data on uptake of home care in 2007 from national care registries, which were combined with fiscal registry data on income and wealth. Postcode data were used to distinguish between 40 'deprived' districts and all other Dutch districts. RESULTS: In the deprived districts more residents received home care than in other districts. This difference was greatest among residents aged 50 to 69 years. After correction for age, sex and country of origin, the difference was substantial (odds ratio (OR): 1.31). After correction for differences in income this difference was halved (OR: 1.17).The difference was further strongly reduced after correction for wealth (OR: 1.06). In deprived districts there was a higher uptake of domestic care (OR: 1.12) but the inverse was true for personal care (OR: 0.95). The latter was most marked in residents aged 80 and above (OR: 0.88). CONCLUSION: The higher uptake of home care among residents of deprived districts can be attributed to low levels of income and wealth. In the Netherlands, changes in home care arrangements at national and local level should take into account people with financial problems and the districts in which they live.

Escitalopram Decreases Cross-Regional Functional Connectivity within the Default-Mode Network.

The default-mode network (DMN), which comprises medial frontal, temporal and parietal regions, is part of the brain's intrinsic organization. The serotonergic (5-HT) neurotransmitter system projects to DMN regions from midbrain efferents, and manipulation of this system could thus reveal insights into the neurobiological mechanisms of DMN functioning. Here, we investigate intrinsic functional connectivity of the DMN as a function of activity of the serotonergic system, through the administration of the selective serotonin reuptake inhibitor (SSRI) escitalopram. We quantified DMN functional connectivity using an approach based on dual-regression. Specifically, we decomposed group data of a subset of the functional time series using spatial independent component analysis, and projected the group spatial modes to the same and an independent resting state time series of individual participants. We found no effects of escitalopram on global functional connectivity of the DMN at the map-level; that is, escitalopram did not alter the global functional architecture of the DMN. However, we found that escitalopram decreased DMN regional pairwise connectivity, which included anterior and posterior cingulate cortex, hippocampal complex and lateral parietal regions. Further, regional DMN connectivity covaried with alertness ratings across participants. Our findings show that escitalopram altered intrinsic regional DMN connectivity, which suggests that the serotonergic system plays an important role in DMN connectivity and its contribution to cognition. Pharmacological challenge designs may be a useful addition to resting-state functional MRI to investigate intrinsic brain functional organization.

Smoking initiation, continuation and prevalence in deprived urban areas compared to non-deprived urban areas in The Netherlands.

Previous studies have shown that smoking prevalence is higher in deprived areas than in affluent areas. We aimed to determine whether smoking initiation or continuation contributes most to inequalities in current smoking, and in which population subgroups these area differences were largest. Therefore, we assessed the relationship between area deprivation and current smoking, initiation and continuation in urban areas, in subgroups defined by gender, generation and educational level. Cross-sectional data of 20,603 Dutch adults (18 years and over) living in 963 urban areas in The Netherlands were obtained from the annual national health survey (2003-2009). Three interrelated smoking outcomes were used: current smoking (smokers/total population), initiation (ever-smokers/total population) and continuation (smokers/ever-smokers). Area deprivation was dichotomised; deprived urban areas (as defined by the Dutch government) and non-deprived urban areas (reference group) were distinguished. Multilevel logistic regression models controlled for individual characteristics (including education and income) and tested for interaction with gender, generation and education. After controlling for individual characteristics, odds for smoking were not significantly higher in deprived areas (current smoking: OR = 1.04 [0.92-1.18], initiation: OR = 1.05 [0.93-1.18], continuation: OR = 1.03 [0.88-1.19]). For smoking initiation, significant differences between deprived areas and other areas remained in younger generations (OR = 1.19 [1.02-1.38]) and higher educated (OR = 1.23 [1.04-1.45]) respondents. For continuation and current smoking, after controlling for individual characteristics, no associations were found in any subgroups. In conclusion, area deprivation appears to be independently related to smoking initiation in, respectively, higher educated and younger generations. These results suggest that initiatives to reduce area-level inequalities in smoking should focus on preventing smoking initiation in deprived areas.

Why residents of Dutch deprived neighbourhoods are less likely to be heavy drinkers: the role of individual and contextual characteristics.

BACKGROUND: Earlier research has shown that residents of Dutch deprived neighbourhoods drink less alcohol than people in other areas. We aimed to assess the role of individual and neighbourhood characteristics in a cross-sectional, nationwide, multilevel study. METHODS: Individual data of 30,117 Dutch adults, living in 1722 neighbourhoods across the Netherlands, were obtained from the 2004 to 2009 national health survey (POLS). Chronic heavy alcohol consumption was measured as ≥14 drinks/week for women and ≥21 for men, and episodic heavy drinking as ≥6 drinks/day at least once a week. Neighbourhood deprivation was dichotomous; deprived districts as selected by the Dutch government versus other areas. Multilevel logistic regression models of the association between deprivation and heavy drinking were corrected for age, gender, household composition, population density and potential predictors ethnicity, socioeconomic status (education, income), neighbourhood-level social cohesion and percentage Muslims. RESULTS: The prevalence of heavy drinking was lower in deprived neighbourhoods than in the rest of the Netherlands. This association was found for both chronic and episodic heavy drinking (OR=0.58 (0.47 to 0.72) and OR=0.57 (0.45 to 0.72), respectively). Adding ethnicity to the model reduced these associations by approximately one half. Socioeconomic composition did not contribute to the relationship. The proportion of Muslims explained a small part, while social cohesion explained even less of the association. Stronger associations were observed for women and older adults than for men and younger adults. CONCLUSIONS: The lower prevalence of heavy drinking occurring in deprived areas is largely explained by the ethnicity of neighbourhood residents.

Neighbourhood safety and leisure-time physical activity among Dutch adults: a multilevel perspective.

BACKGROUND: Several neighbourhood elements have been found to be related to leisure-time walking and cycling. However, the association with neighbourhood safety remains unclear. This study aimed to assess the association of neighbourhood-level safety with leisure-time walking and cycling among Dutch adults. METHODS: Data were derived from the national health survey (POLS) 2006-2009, with valid data on 20046 respondents residing in 2127 neighbourhoods. Multilevel logistic regression models were used to examine the association between neighbourhood-level safety (general safety and specific safety components: physical disorder, social disorder, crime-related fear, traffic safety) and residents' engagement in outdoor leisure-time walking and cycling for at least 30 minutes per week. RESULTS: An increase in neighbourhood safety (both general safety and each of the safety components) was significantly associated with an increase in leisure-time cycling participation. Associations were strongest for general safety and among older women. In the general population, neighbourhood safety was not significantly associated with leisure-time walking. However, among younger and older adult men and lower educated individuals, an increase in general safety was associated with a decrease in leisure-time walking participation. CONCLUSIONS: In the Netherlands, neighbourhood safety appears to be related to leisure-time cycling but not to walking. Leisure-time cycling may best be encouraged by improving different safety components at once, rather than focusing on one safety aspect such as traffic safety. Special attention is needed for older women.

The association between neighborhood disorder, social cohesion and hazardous alcohol use: a national multilevel study.

BACKGROUND: Evidence on associations of alcohol use with neighborhood disorder and social cohesion is limited. The aim of this study was to further investigate these associations. METHODS: Individual data of 14,258 Dutch adults, living in 1546 neighborhoods across The Netherlands, were obtained from the 2006 to 2009 national health survey (POLS). Data on neighborhood disorder and social cohesion were derived from the 2006 Netherlands Housing Research (WoON). Hazardous drinking was measured as: ≥14, ≥21, and ≥28 drinks/week for women, and ≥21, ≥28, and ≥35 for men. Multilevel logistic regression models were adjusted for age, gender, ethnicity, marital status, education, income, wealth, predominant neighborhood religion, and population density. Potential mediation of psychological distress (depression and anxiety) and general mental health (MHI-5 score) was tested. RESULTS: High neighborhood disorder was associated with more hazardous alcohol use for women (OR cut-off 3: 3.72 [2.03-6.83]), but not for men (OR cut-off 3: 1.08 [0.72-1.62]). There was no mediation by psychological distress, and modest mediation by general mental health. Social cohesion had no linear association with hazardous alcohol use, but for males moderate social cohesion was associated with more hazardous alcohol use (OR cut-off 1: 1.29 [1.08-1.53]). In predominantly Protestant neighborhoods this association seemed weaker. CONCLUSIONS: Hazardous alcohol use seems to have a stronger and more consistent relationship with neighborhood disorder than with social cohesion. This suggests that negative aspects of the social environment have more impact on the prevalence of hazardous alcohol use than positive factors related to sociability and support.

MDMA intoxication and verbal memory performance: a placebo-controlled pharmaco-MRI study.

The aim of the present study was to identify the neural substrate underlying memory impairment due to a single dose of MDMA (3,4-methylenedioxymethamphetamine) by means of pharmaco-MRI. Based on previous behavioral results it was hypothesized that this deficit could be attributed to a specific influence of MDMA on encoding. Fourteen Ecstasy users participated in this double-blind, placebo-controlled, within-subject study with two treatment conditions: MDMA (75 mg) and placebo. Memory performance was tested by means of a word learning task including two words lists, one addressing reading processes (control task, CWL) and a second (experimental task, EWL) addressing encoding and reading processes. Behavioral data showed that under the influence of MDMA, EWL performance was worse than placebo. Imaging data showed that Encoding was situated mainly in (pre)frontal, temporal and parietal areas. MDMA by Encoding interaction was situated in three areas: the left middle frontal gyrus (BA10), the right fusiform gyrus (BA19), and the left cuneus (BA18). Behavioral and functional data only correlated in BA10. It appeared that EWL performance caused BOLD signal change in BA10 during placebo treatment but not during MDMA intoxication. It is concluded that MDMA influences middle frontal gyrus processes resulting in impoverished memory encoding.

Involvement of inferior parietal lobules in prospective memory impairment during acute MDMA (ecstasy) intoxication: an event-related fMRI study.

Prospective memory refers to the realization of delayed intentions. Several studies have shown that 3,4-methylenedioxy-methamphetamine (MDMA) users perform worse on measures of prospective memory as compared to nondrug users. Interpretation of these data may be limited because of polydrug use, psychosocial stressors, and increased psychopathology that have been reported in MDMA users. This study was designed to directly assess the pharmacological effect of MDMA on prospective memory and brain activity in a double-blind, placebo-controlled, cross-over study. Twelve recreational MDMA users received MDMA 75 mg and placebo and performed an objective prospective memory task during functional imaging. During prospective memory task performance subjects were engaged in a foreground task that consisted of a simple reaction time to visual stimuli (Go trials) and a prospective task of withholding a response during trials that were part of a dynamic memory set (No go trials). Behavioral data showed that a single dose of MDMA increased prospective memory failures in the No go trials, and that number of prospective memory failures was positively correlated to MDMA concentration in plasma. Functional imaging showed that MDMA decreased BOLD activation during Go trials in the thalamus (left), putamen (left), precuneus (left), and the inferior parietal lobules (bilateral), as compared to placebo. During No go trials, MDMA reduced BOLD deactivation in the inferior parietal lobules (bilateral), as compared to placebo. It is concluded that the loss of deactivation in inferior parietal lobules may account for increments in memory failures observed during MDMA intoxication.

Sustained attention and serotonin: a pharmaco-fMRI study.

OBJECTIVE: Evidence suggests that stimulation of serotonergic function in healthy humans causes an impairment of sustained attention. The present study assessed the influence of increased serotonin levels on brain areas involved in sustained attention. METHODS: Ten healthy volunteers (5 females, 5 males) received the selective serotonin reuptake inhibitor (SSRI) escitalopram (20 mg) and placebo in a balanced, double blind, two-way crossover design. Participants performed the Mackworth Clock Test to measure sustained attention during functional MRI measurements at 3 Tesla. Subjective measurements after pharmacological manipulation were conducted with the Bond and Lader Questionnaire. RESULTS: Independent of treatment, brain areas associated with task performance on a sustained attention task were activated, including right prefrontal and parietal areas. After escitalopram administration, less activation was shown in the caudate nucleus, thalamus, and frontal areas. No effect of escitalopram was shown on behavioral data although subjective measurements showed decreased alertness after escitalopram. CONCLUSIONS: The results of the current pharmaco-functional magnetic resonance imaging (fMRI) study give a first indication of involvement of serotonin in sustained attention through modulating activation of selective brain areas including the thalamus and caudate nucleus. Possibly, these areas are involved in a subcortical network for sustained attention, but further research is necessary.

The role of 5-HT1a and 5-HT2a receptors in attention and motor control: a mechanistic study in healthy volunteers.

RATIONALE: Various studies have demonstrated a modulating role for serotonin in attention. Selective serotonin inhibitors have repeatedly been shown to impair performance in sustained attention tasks. OBJECTIVES: To assess the contribution of serotonin reuptake inhibition and specific blockade of the pre-synaptic 5-HT(1a) receptor and the 5-HT(2a) receptor to deficits in attention. MATERIALS AND METHODS: The study was conducted according to a randomized, double-blind, placebo controlled, four-way crossover design including 16 healthy volunteers. Treatments consisted of oral administration of the selective serotonin reuptake inhibitor (SSRI) escitalopram 20 mg + placebo; escitalopram 20 mg + ketanserin (5-HT(2a) antagonist), 50 mg; escitalopram 20 mg + pindolol (5-HT(1a) antagonist) 10 mg; and placebo + placebo on four separate days. A range of performance tasks were conducted to assess the subjects' attention and motor functions. RESULTS: Escitalopram administered alone impaired tracking performance in a divided attention task. The combination of escitalopram and pindolol and escitalopram and ketanserin impaired divided attention as compared to placebo. In addition, escitalopram and ketanserin impaired sustained attention. Divided attention impairment observed after combined treatments did not significantly differ from impairments after escitalopram alone. Sustained attention impairment observed after combined escitalopram and ketanserin significantly differed from escitalopram alone. CONCLUSIONS: 5HT(1a) blockade hardly affected SSRI effects on attention. Additional 5HT(2a) blockade, however, produced impairments of sustained attention and motor impulse control.

Driving impairment in depressed patients receiving long-term antidepressant treatment.

BACKGROUND: Depression is a common mental disorder with cognitive deficits, but little information is available on the effects of antidepressant treatment on driving performance in depressed patients. AIMS: Assessing actual driving performance and cognition of depressed patients receiving long-term antidepressant treatment. MATERIALS AND METHODS: Performance was assessed in depressed patients receiving selective serotonin reuptake inhibitor (SSRI) or serotonin and noradrenalin reuptake inhibitor (SNRI) treatment for 6-52 weeks and in matched healthy controls by means of two standardised on-the-road driving tests and laboratory tests of cognition. RESULTS: Data showed poorer driving performance as indicated by a higher standard deviation of lateral position or 'weaving motion' in medicated patients relative to controls. Time to speed adaptation and critical flicker fusion threshold were also impaired in medicated patients. The Hamilton Depression Rating Scale scores in medicated patients were significantly higher as compared to that of controls. No other significant results between the two groups were demonstrated on the variables of the driving tests and laboratory tests of cognition. CONCLUSIONS: The depressed patients receiving long-term treatment with SSRI- and SNRI-type antidepressants show impaired driving performance. This impairment in driving performance can probably be attributed to residual depressive symptoms instead of the antidepressant treatment.

Actual driving performance and psychomotor function in healthy subjects after acute and subchronic treatment with escitalopram, mirtazapine, and placebo: a crossover trial.

OBJECTIVE: The effects of escitalopram 10 to 20 mg/day and mirtazapine 30 to 45 mg/day on actual driving and psychomotor performance of 18 healthy subjects were determined in a randomized, double-blind, placebo-controlled, multiple-dose, 3-way crossover trial. METHOD: Each treatment period lasted for 15 days and was separated from the next period by a washout period of at least 13 days. Subjects received an evening dose of escitalopram 10 mg, mirtazapine 30 mg, or placebo from days 1 to 7 and an evening dose of escitalopram 20 mg, mirtazapine 45 mg, or placebo from days 8 to 15. On days 2, 9, and 16, reflecting acute period, dose increase, and steady state, respectively, the Road Tracking Test was performed. The main parameter was standard deviation of lateral position. Psychomotor performance was also assessed on days 2, 9, and 16 by laboratory computer tasks. Subjective sleep quality was measured with the Groninger Sleep Quality Scale, and mood was measured by visual analogue scales. RESULTS: Treatment differences were apparent during the acute treatment period, in which subjects treated with mirtazapine 30 mg performed less well on the driving test as compared to placebo. The Divided Attention Task results also revealed a significant increase in tracking error after a single dose of mirtazapine 30 mg as compared to placebo. Mirtazapine decreased feelings of alertness and contentedness. Mirtazapine did not affect performance on days 9 and 16 of treatment. Escitalopram did not affect driving, psychomotor performance, or subjective mood throughout treatment. CONCLUSION: Driving performance, as well as psychomotor functioning, was not affected by escitalopram treatment in healthy subjects. Driving performance was significantly impaired after ingestion of mirtazapine 30 mg during the acute treatment period.