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The mesolimbic dopaminergic system has been implicated in two kinds of reward processing, one in reinforcement learning (e.g prediction error) and another in incentive salience attribution (e.g. cue-reactivity). Both functions have been implicated in alcohol dependence with the former contributing to the persistence of chronic alcohol intake despite severe negative consequences and the latter playing a crucial role in cue-induced craving and relapse. The bicentric study “Learning in alcohol dependence (LeAD)” aims to bridge a gap between these processes by investigating reinforcement learning mechanisms and the influence that Pavlovian cues exert over behavior. We here demonstrate that alcohol dependent subjects show alterations in goal-directed, model-based reinforcement learning (Sebold et al., 2014) and demonstrate that prospective relapsing patients show reductions in the medial prefrontal cortex activation during goal-directed control. Moreover we show that in alcohol dependent patients compared to healthy controls, Pavlovian cues exert pronounced control over behavior (Garbusow et al., 2016). Again, prospective relapsing patients showed increased Nucleus accumbens activation during these cue-induced responses. These findings point to an important role of the mesolimbic dopaminergic system as a predictor of treatment outcome in alcohol dependence.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Accumulating evidence shows that a propensity towards a pro-inflammatory status in the brain plays an important role in schizophrenia. Anti-inflammatory drugs might compensate this propensity. This study provides an update regarding the efficacy of agents with some anti-inflammatory actions for schizophrenia symptoms tested in randomized controlled trials (RCTs).
PubMed, Embase, the National Institutes of Health website (http://www.clinicaltrials.gov), and the Cochrane Database of Systematic Reviews were systematically searched for RCTs that investigated clinical outcomes.
Our search yielded 56 studies that provided information on the efficacy of the following components on symptom severity: aspirin, bexarotene, celecoxib, davunetide, dextromethorphan, estrogens, fatty acids, melatonin, minocycline, N-acetylcysteine (NAC), pioglitazone, piracetam, pregnenolone, statins, varenicline, and withania somnifera extract. The results of aspirin [mean weighted effect size (ES): 0.30; n = 270; 95% CI (CI) 0.06–0.54], estrogens (ES: 0.78; n = 723; CI 0.36–1.19), minocycline (ES: 0.40; n = 946; CI 0.11–0.68), and NAC (ES: 1.00; n = 442; CI 0.60–1.41) were significant in meta-analysis of at least two studies. Subgroup analysis yielded larger positive effects for first-episode psychosis (FEP) or early-phase schizophrenia studies. Bexarotene, celecoxib, davunetide, dextromethorphan, fatty acids, pregnenolone, statins, and varenicline showed no significant effect.
Some, but not all agents with anti-inflammatory properties showed efficacy. Effective agents were aspirin, estrogens, minocycline, and NAC. We observed greater beneficial results on symptom severity in FEP or early-phase schizophrenia.
The smr and qacA/B genes in Staphylococcus aureus confer tolerance to antiseptics and are associated with nosocomial acquisition of infection and underlying medical conditions. Such antiseptic tolerance (AT) genes have also been reported in coagulase-negative staphylococci (CoNS) and enterococci, however, few data are available regarding their prevalence. We sought to describe the frequency of AT genes among bloodstream isolates of S. aureus, CoNS and enterococci at Texas Children’s Hospital (TCH).
Banked CoNS, S. aureus and enterococci isolated from blood cultures collected bewteen October 1, 2016, and October 1, 2017, were obtained from the TCH clinical microbiology laboratory. All isolates underwent polymerase chain reaction (PCR) assay for the qacA/B and smr genes. Medical records were reviewed for all cases.
In total, 103 CoNS, 19 Enterococcus spp, and 119 S. aureus isolates were included in the study, and 80.6% of the CoNS possessed at least 1 AT gene compared to 37% of S. aureus and 43.8% of E. faecalis isolates (P < .001). Among CoNS bloodstream isolates, the presence of either AT gene was strongly associated with nosocomial infection (P < .001). The AT genes in S. aureus were associated with nosocomial infection (P = .025) as well as the diagnosis of central-line–associated bloodstream infection (CLABSI; P = .04) and recent hospitalizations (P < .001). We found no correlation with genotypic AT in E. faecalis and any clinical variable we examined.
Antiseptic tolerance is common among bloodstream staphylococci and E. faecalis isolates at TCH. Among CoNS, the presence of AT genes is strongly correlated with nosocomial acquisition of infection, consistent with previous studies in S. aureus. These data suggest that the healthcare environment contributes to AT among staphylococci.
Strategies are needed to improve the dietary habits of children. The aim of the present study was to evaluate the effect of implementing a school food programme on the dietary quality of lunches consumed by school children aged 7–13 years compared with packed lunches brought from home. A secondary objective was to investigate if a possible effect would differ between the younger children and the older. A quasi-experimental study design with four intervention schools and four matched control schools was conducted. In total, 984 school children participated. Data on packed lunches were collected at baseline. At the 1st follow-up the children in the intervention schools were offered free school meals and at the 2nd follow-up children paid for their school meals. The control group had packed lunches at all measurements. A digital photographic method combined with a Meal Index of dietary Quality (Meal IQ) was used for dietary assessment. Multilevel modelling was employed for data analyses. The quality of dietary intake was improved when free school meals were offered (P = 0·004); if the school meals were paid for the use was limited and no difference in change in dietary quality was found (P = 0·343). The school food programme had no difference in effect according to age (P = 0·083). In conclusion, offering a free school meal had a positive effect on dietary quality of the lunches consumed by school children aged 7–13 years. No effect was measured when the school meals were not provided for free. The dietary effect did not depend on age.
Studies investigating the underlying mechanisms of hallucinations in patients with schizophrenia suggest that an imbalance in top-down expectations v. bottom-up processing underlies these errors in perception. This study evaluates this hypothesis by testing if individuals drawn from the general population who have had auditory hallucinations (AH) have more misperceptions in auditory language perception than those who have never hallucinated.
We used an online survey to determine the presence of hallucinations. Participants filled out the Questionnaire for Psychotic Experiences and participated in an auditory verbal recognition task to assess both correct perceptions (hits) and misperceptions (false alarms). A hearing test was performed to screen for hearing problems.
A total of 5115 individuals from the general Dutch population participated in this study. Participants who reported AH in the week preceding the test had a higher false alarm rate in their auditory perception compared with those without such (recent) experiences. The more recent the AH were experienced, the more mistakes participants made. While the presence of verbal AH (AVH) was predictive for false alarm rate in auditory language perception, the presence of non-verbal or visual hallucinations were not.
The presence of AVH predicted false alarm rate in auditory language perception, whereas the presence of non-verbal auditory or visual hallucinations was not, suggesting that enhanced top-down processing does not transfer across modalities. More false alarms were observed in participants who reported more recent AVHs. This is in line with models of enhanced influence of top-down expectations in persons who hallucinate.
Similar to visual hallucinations in visually impaired patients, auditory hallucinations are often suggested to occur in adults with hearing impairment. However, research on this association is limited. This observational, cross-sectional study tested whether auditory hallucinations are associated with hearing impairment, by assessing their prevalence in an adult population with various degrees of objectified hearing impairment.
Hallucination presence was determined in 1007 subjects aged 18–92, who were referred for audiometric testing to the Department of ENT-Audiology, University Medical Center Utrecht, the Netherlands. The presence and severity of hearing impairment were calculated using mean air conduction thresholds from the most recent pure tone audiometry.
Out of 829 participants with hearing impairment, 16.2% (n = 134) had experienced auditory hallucinations in the past 4 weeks; significantly more than the non-impaired group [5.8%; n = 10/173; p < 0.001, odds ratio 3.2 (95% confidence interval 1.6–6.2)]. Prevalence of auditory hallucinations significantly increased with categorized severity of impairment, with rates up to 24% in the most profoundly impaired group (p < 0.001). The corrected odds of hallucination presence increased 1.02 times for each dB of impairment in the best ear. Auditory hallucinations mostly consisted of voices (51%), music (36%), and doorbells or telephones (24%).
Our findings reveal that auditory hallucinations are common among patients with hearing impairment, and increase with impairment severity. Although more research on potential confounding factors is necessary, clinicians should be aware of this phenomenon, by inquiring after hallucinations in hearing-impaired patients and, conversely, assessing hearing impairment in patients with auditory hallucinations, since it may be a treatable factor.
Decline in cognitive functioning precedes the first psychotic episode in the course of schizophrenia and is considered a hallmark symptom of the disorder. Given the low incidence of schizophrenia, it remains a challenge to investigate whether cognitive decline coincides with disease-related changes in brain structure, such as white matter abnormalities. The 22q11.2 deletion syndrome (22q11DS) is an appealing model in this context, as 25% of patients develop psychosis. Furthermore, we recently showed that cognitive decline also precedes the onset of psychosis in individuals with 22q11DS. Here, we investigate whether the early cognitive decline in patients with 22q11DS is associated with alterations in white matter microstructure.
We compared the fractional anisotropy (FA) of white matter in 22q11DS patients with cognitive decline [n = 16; −18.34 (15.8) VIQ percentile points over 6.80 (2.39) years] to 22q11DS patients without cognitive decline [n = 18; 17.71 (20.17) VIQ percentile points over 5.27 (2.03) years] by applying an atlas-based approach to diffusion-weighted imaging data.
FA was significantly increased (p < 0.05, FDR) in 22q11DS patients with a cognitive decline in the bilateral superior longitudinal fasciculus, the bilateral cingulum bundle, all subcomponents of the left internal capsule and the left superior frontal-occipital fasciculus as compared with 22q11DS patients without cognitive decline.
Within 22q11DS, the early cognitive decline is associated with microstructural differences in white matter. At the mean age of 17.8 years, these changes are reflected in increased FA in several tracts. We hypothesize that similar brain alterations associated with cognitive decline take place early in the trajectory of schizophrenia.
Auditory Hallucinations (AH) are nowadays regarded as symptoms following a continuum; from a (transient) phenomenon in healthy individuals on one end to a symptom of (psychiatric) illnesses at the other. An accumulating number of epidemiological studies focused on the prevalence of AH in the general population, but results vary widely. The current meta-analysis aims to synthesize existing evidence on lifetime prevalence of AH across the lifespan.
We conducted a quantitative review and meta-analysis according to PRISMA guidelines. Studies were combined to calculate a mean lifetime general population AH prevalence rate. Moreover, prevalences were calculated for four age groups: children (5–12 years), adolescents (13–17 years), adults (18–60 years) and elderly (⩾60 years).
We retrieved 25 study samples including 84 711 participants. Mean lifetime prevalence rate of AH was 9.6% (95% CI 6.7–13.6%). The mean lifetime prevalence was similar in children (12.7%) and adolescents (12.4%), but these two groups differed significantly from the adults (5.8%) and the elderly (4.5%). Significant heterogeneity indicated that there is still dispersion in true prevalence rates between studies, even within the different age categories.
Current meta-analysis shows that AH are quite common (up to one in ten individuals) in the general population during lifetime, with children and adolescents reporting these experiences significantly more often compared with adults and elderly. Large follow-up studies on the longitudinal course of AH are needed to reveal associated risk and resilience factors.
Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.
This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).
Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.
Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
In patients with borderline personality disorder (BPD), about 22–50% experience auditory verbal hallucinations (AVH). However, the impact of these hallucinations on suicidal ideation, suicide attempts, crisis-service interventions, and hospital admissions is unknown.
In a cross-sectional design, data were collected with the Psychotic Symptom Rating Scales (PSYRATS) and the MINI International Neuropsychiatric Interview Plus, as well as from the medical records of a convenience sample of outpatients fulfilling the DSM-IV criteria for BPD.
Of the 89 included patients, 27 experienced AVH. In the latter group, the presence of AVH was associated with a significantly higher incidence of suicidal plans and attempts in the month prior to study participation, more hospitalisations, and a shorter interval until hospitalisation. All subscales of the PSYRATS correlated positively with suicide plans, while the phenomenological and emotional subscales also correlated positively with suicide attempts. Moreover, higher scores on the emotional subscale were associated with more hospital admissions.
AVH experienced by patients with BPD might constitute a risk factor for suicide plans and attempts, and hospitalisation. This finding emphasises that this population requires adequate clinical attention, as well as effective treatment for AVH.
Auditory verbal hallucinations (AVH) are a frequently occurring phenomenon in the general population and are considered a psychotic symptom when presented in the context of a psychiatric disorder. Neuroimaging literature has shown that AVH are subserved by a variety of alterations in brain structure and function, which primarily concentrate around brain regions associated with the processing of auditory verbal stimuli and with executive control functions. However, the direction of association between AVH and brain function remains equivocal in certain research areas and needs to be carefully reviewed and interpreted. When AVH have significant impact on daily functioning, several efficacious treatments can be attempted such as antipsychotic medication, brain stimulation and cognitive–behavioural therapy. Interestingly, the neural correlates of these treatments largely overlap with brain regions involved in AVH. This suggests that the efficacy of treatment corresponds to a normalization of AVH-related brain activity. In this selected review, we give a compact yet comprehensive overview of the structural and functional neuroimaging literature on AVH, with a special focus on the neural correlates of efficacious treatment.
Previously, we described 103 adults (mean age 41 years) who experienced frequent, auditory verbal hallucinations (AVH), in the absence of a need for mental healthcare. Importantly, these adults were largely past the peak incidence age for psychosis (15–35 years). It is unclear if these older individuals with AVH are still at increased risk for psychosis or other psychopathology. To address this question, we conducted a 5-year follow-up of previously included individuals (103 with AVH, 60 controls).
Eighty-one adults with AVH (78.6%) and forty-nine controls (81.7%) could be contacted and were willing to participate. Participants were screened for psychosis and a need for mental healthcare at follow-up using the Comprehensive Assessment of Symptoms and History interview (CASH). Need for mental healthcare was defined as a clinical diagnosis as identified using the CASH and/or treatment by a mental healthcare specialist. Phenomenology of AVH was assessed with the PSYRATS Auditory Hallucinations Rating Scale.
Five individuals with AVH (6.2%) had developed psychosis and 32 (39.5%) had developed a need for mental healthcare. Voice-related distress at baseline significantly predicted need for mental healthcare. AVH persisted in most individuals (86.4%), without significant changes in phenomenology. None of the controls had developed psychotic symptoms, and need for mental healthcare (n = 6, 12.2%) was significantly lower in this group.
These findings suggest that frequent AVH in non-psychotic adults past the peak incidence age for psychosis constitute a rather static symptom and that individuals with AVH may be best viewed as situated on a need for care continuum.
The content of vitamin D in pork produced in conventional systems depends on the vitamin D concentration in the pig feed. Both vitamin D3 and 25-hydroxyvitamin D3 (25(OH)D3) are essential sources of dietary vitamin D; however, bioavailability assessed by serum 25(OH)D3 concentration is reported to be different between the two sources. Furthermore, the relationship between serum 25(OH)D3 level and the tissue content of vitamin D3 and 25(OH)D3 is unknown. The objective of this study was to investigate the potential of increasing the content of vitamin D in different pig tissues by increasing the levels of vitamin D3 and 25(OH)D3 in the pig feed for 49 d before slaughter. Concurrently, the 25(OH)D3 level in serum was investigated as a biomarker to assess the content of vitamin D3 and 25(OH)D3 in pig tissues. Adipose tissue, white and red muscle, the liver and serum were sampled from pigs fed feed containing either vitamin D3 or 25(OH)D3 at 5, 20, 35 or 50 µg/kg feed for 7 weeks before slaughter. The tissue 25(OH)D3 level was significantly higher in the pigs fed 25(OH)D3 compared with those fed vitamin D3, while the tissue vitamin D3 level was higher in the pigs fed vitamin D3 compared with those fed 25(OH)D3. The content of 25(OH)D3 in the different tissues fully correlated with the serum 25(OH)D3 level, whereas the correlation between the tissue content of vitamin D3 and serum 25(OH)D3 was dependent on the source of the ingested vitamin D3.
Despite limited research on single parent dating, one study found that perceptions of single adults in an online dating profile varied by their gender, number of children, and parental status (Sommer, Plumm, Terrance, & Tubré, 2013). This information may affect perceived desirability and dateability for potential mates. The current study explored the effects of a potential mate's parental and previous relationship status, as well as participant parental status, on the participants’ perceptions of a potential dating partner via an online dating profile. Participants (n = 251), who were single and looking to date, were asked to read a brief ‘About the person’ section of a dating profile and rate how they viewed the person on general positive traits, childrearing ability, family relationships, dating appeal, future investment, and stress. Results indicated that single parents and non-parents alike preferred partners with no children. Additionally, single parents viewed being divorced more positively than single adults who are not parents, whereas single adults with no children viewed the profile with no previous relationship most positively. Future research should focus on the participant's intent for viewing and selecting a mate through the means of online dating.
Animal slurry is separated in order to avoid excessive nitrogen, phosphorus and potassium (NPK) fertilization of crops in the field. To enhance fertilizer efficiency further, slurry and its separation products may be acidified, for instance in animal houses. The current study quantified the effects of these treatments, both individually and in combination, on fertilizer efficiency, energy production and heavy metal accumulation as a result of manure management. Acidification increased the availability of N to plants in the manure applied, and provided a better match between plant-available NPK in the manure and separation fraction applied to fields and crop need. Total biogas production was not affected by separation, whereas acidification reduced biogas production because the process was inhibited by a low pH and a high sulphur concentration. The amount of copper applied per hectare in the liquid manure to the wheat field was lower than the amount taken up and more zink and copper was applied in the solid fraction to maize field than taken up. The transportation and field application of solids and liquids did not increase management costs when compared to the transportation of slurry alone, but the investment and running costs of separators and manure acidification increased overall management costs.
As of January 2014, 26 states had chosen to expand Medicaid under the Affordable Care Act (ACA) to cover individuals with incomes up to 138% of the federal poverty level. In these states, Medicaid agencies are facing one of the largest implementation challenges in the program’s history. We undertook a survey of high-ranking Medicaid officials in these states to assess their priorities, expectations, and programmatic decisions related to the coming expansion.
The Medicaid expansion poses major challenges in the domains of enrollment, management of health care costs, and providing adequate access to services for beneficiaries. Previous research has documented that millions of individuals eligible for Medicaid are currently not enrolled and remain uninsured, suggesting that state outreach strategies may underpin the success or failure of the ACA’s coverage expansion.