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Catechol-O-methyltransferase (COMT) has a central role in brain dopamine, noradrenalin and adrenalin signaling, and has been suggested to be involved in the pathogenesis and pharmacological treatment of affective disorders. The functional single nucleotide polymorphism (SNP) in exon 4 (Val158Met, rs4680) influences the COMT enzyme activity. The Val158Met polymorphism is a commonly studied variant in psychiatric genetics, and initial studies in schizophrenia and bipolar disorder presented evidence for association with the Met allele. In unipolar depression, while some of the investigations point at an association between the Met/Met genotype and others have found a link between the Val/Val genotype and depression, most of the studies cannot detect any difference in Val158Met allele frequency between depressed individuals and controls.
In the present study, we further elucidated the impact of COMT polymorphisms including the Val158Met in MDD. We investigated 1,250 subjects with DSM-IV and/or ICD-10 diagnosis of major depression (MDD), and 1,589 control subjects from UK. A total of 24 SNPs spanning the COMT gene were successfully genotyped using the Illumina HumaHap610-Quad Beadchip (22 SNPs), SNPlex™ genotyping system (1 SNP), and Sequenom MassARRAY® iPLEX Gold (1 SNP). Statistical analyses were implemented using PASW Statistics18, FINETTI (http://ihg.gsf.de/cgi-bin/hw/hwa1.pl), UNPHASED version 3.0.10 program and Haploview 4.0 program.
Neither single-marker nor haplotypic association was found with the functional Val158Met polymorphism or with any of the other SNPs genotyped. Our findings do not provide evidence that COMT plays a role in MDD or that this gene explains part of the genetic overlap with bipolar disorder.
According to Oedegaard et al. (2010) the co-morbidity of migraine and bipolar disorder (BPD) is well documented in numerous epidemiological and clinical studies, and there are clear pathophysiological similarities. Interestingly, in a genome-wide scan, Lea et al. (2005) identified a susceptibility locus for a severe heritable form of common migraine on chromosome 3q29. With respect to BPD, a susceptibility region on chromosome 3q29 was identified in a genome-wide linkage scan (Bailer et al. 2002) and follow-up linkage analysis (Schosser et al. 2004). These findings were also supported by further fine-mapping of this region (Schosser et al. 2007). Since 3q29 is among the chromosomal regions implicated in migraine and bipolar linkage studies, the aim of the current study is to test for 3q29 association of migraine in sample of patients with BPD. The sample consists of 463 patients with a diagnosis of BPD (34.63% men, 65.37% women; mean age ± SD: 48.01 ± 11.26), as defined by the Diagnostic and Statistical Manual 4th edition operational criteria (DSM-IV) and the International Classification of Diseases 10th edition operational criteria (ICD-10), derived from the Bipolar Affective Disorder Case Control Study (BACCS). A total of 51 SNPs in the region of the 3q29 were genotyped using Sequenom MassARRAY® iPLEX Gold and tested for association with migraine. The results of this association study investigating the 3q29 region in a sample of patients with BPD will be presented.
As awareness of ADHD has increased throughout the world, interest has grown beyond the constellation of ADHD symptoms, including long-term effects and impact on people's lives.
To examine the consequences of childhood ADHD and the relevance of these outcomes in different world regions.
This analysis examined the publication trends of studies of long-term outcomes of ADHD over time and among world regions.
Study identification followed Cochrane guidelines. Twelve databases were searched for reports published in English 1980–2010. Limiting criteria were designed to maximize study inclusion while maintaining a high level of study rigor: the studies were to
(1) be peer-reviewed,
(2) be primary study reports,
(3) include a comparator group or baseline, and
(4) report outcome results measured for a mean of 8 years (prospective studies, range of all studies was 6 months-40 years) after the start of the study, in late adolescence, or adulthood.
The fully-defined electronic search yielded 4615 citations, which were then reviewed manually based on the titles and abstracts, yielding a final of 371 studies.
Study publication trends analysed included: publication year, country and world region of origin, outcome types, and study types. In general, the numbers of studies published per year globally has increased substantially (from 2 in 1980 to more than 40/year in 2007 and 2008) with differences observed between Europe and North America.
Analysis of publication trends can provide insight into outcomes of ADHD and the focus of specific world regions.
As awareness of ADHD has increased worldwide, interest has grown beyond the constellation of ADHD symptoms, to include long-term impact on people's lives and society in general.
Examine the results of studies of long-term life consequences of ADHD.
To identify areas of life affected long-term by ADHD and differences in outcomes with and without ADHD treatment.
Following Cochrane guidelines, 12 databases were searched for studies published in English (1980–2010). Limiting criteria maximized study inclusion while maintaining high study rigor: (1) peer-reviewed, (2) primary study reports, (3) including a comparator condition, and (4) reporting long-term outcomes (mean 8 years, range 6 months-40 years from study start for prospective studies; subjects in adolescence or adulthood for retrospective or cross-sectional studies). The fully-defined electronic search yielded 4615 citations. Manual review based on titles and abstracts yielded 340 studies included in this analysis of outcomes.
The majority of studies (86%, 243 of 281; studies of untreated ADHD only) showed that untreated ADHD has substantial negative long-term outcomes, encompassing nine broad-ranging areas of life: non-medicinal drug use/addictive behaviour, antisocial behaviour, academic achievement, occupational achievement, public services use, self-esteem, social function, obesity, and driving outcomes. In contrast, most studies including ADHD pharmacotherapy and/or non-pharmacotherapy (94%, 46 of 49) showed that compared with baseline or untreated ADHD, long-term outcomes improved or stabilized with treatment of ADHD.
ADHD has notable negative long-term consequences, and this negative impact may be reduced with treatment of ADHD. Supported by Shire Development Inc.
Animal research suggests that weight gain may be caused by olanzapine-induced melatonin suppression. We conducted a pilot study of psychiatric patients treated with olanzapine to examine if melatonin was suppressed and if so the dose needed to replace this deficit. The relationship between melatonin and metabolic indices was also examined.
Ten patients with schizophrenia (N=3), schizoaffective disorder (N=3), or bipolar disorder (N=4) completed the study. All patients were male, average age 50.6 years. Patients were treated with olanzapine for 5 weeks, then randomized to either 0.3mg (N=4) or 3mg (N=6) of melatonin supplementation in addition to the olanzapine for another 6 weeks. We obtained baseline, week-6, and week-12 measures of the major metabolite of melatonin in the urine, 6-Sulfatoxymelatonin (aMT6s) adjusted for creatinine excretion. We measures weekly weight, glycemia, cholesterol, and triglycerides.
Olanzapine treatment was associated with a trend toward decreases in melatonin from baseline to week-6 (p=.14). Analysis of a subsample of patients diagnosed with schizoaffective or bipolar disorder showed significant decreases from baseline to week-6 (p=.02). Both supplementation with melatonin by 0.3mg and 3mg increased urinary melatonin levels from week-6 to week-12 (p=.12 and p=.02 respectively). Total cholesterol increased initially but demonstrated a trend for decrease when melatonin was supplemented (p=.10).
Olanzapine appears to be related to melatonin suppression. Melatonin supplementation reverses this suppression and may have the potential to reverse metabolic effects associated with olanzapine. Further studies are needed to examine the metabolic effects of olanzapine with melatonin.
Neurobiological models of auditory verbal hallucination (AVH) have been advanced by symptom capture functional magnetic resonance imaging (fMRI), where participants self-report hallucinations during scanning. To date, regions implicated are those involved with language, memory and emotion. However, previous studies focus on chronic schizophrenia, thus are limited by factors, such as medication use and illness duration. Studies also lack detailed phenomenological descriptions of AVHs. This study investigated the neural correlates of AVHs in patients with first episode psychosis (FEP) using symptom capture fMRI with a rich description of AVHs. We hypothesised that intrusive AVHs would be associated with dysfunctional salience network activity.
Sixteen FEP patients with frequent AVH completed four psychometrically validated tools to provide an objective measure of the nature of their AVHs. They then underwent fMRI symptom capture, utilising general linear models analysis to compare activity during AVH to the resting brain.
Symptom capture of AVH was achieved in nine patients who reported intrusive, malevolent and uncontrollable AVHs. Significant activity in the right insula and superior temporal gyrus (cluster size 141 mm3), and the left parahippocampal and lingual gyri (cluster size 121 mm3), P < 0.05 FDR corrected, were recorded during the experience of AVHs.
These results suggest salience network dysfunction (in the right insula) together with memory and language processing area activation in intrusive, malevolent AVHs in FEP. This finding concurs with others from chronic schizophrenia, suggesting these processes are intrinsic to psychosis itself and not related to length of illness or prolonged exposure to antipsychotic medication.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Objectives: Research has shown that analyzing intrusion errors generated on verbal learning and memory measures is helpful for distinguishing between the memory disorders associated with Alzheimer’s disease (AD) and other neurological disorders, including Huntington’s disease (HD). Moreover, preliminary evidence suggests that certain clinical populations may be prone to exhibit different types of intrusion errors. Methods: We examined the prevalence of two new California Verbal Learning Test-3 (CVLT-3) intrusion subtypes – across-trial novel intrusions and across/within trial repeated intrusions – in individuals with AD or HD. We hypothesized that the encoding/storage impairment associated with medial-temporal involvement in AD would result in a greater number of novel intrusions on the delayed recall trials of the CVLT-3, whereas the executive dysfunction associated with subcortical-frontal involvement in HD would result in a greater number of repeated intrusions across trials. Results: The AD group generated significantly more across-trial novel intrusions than across/within trial repeated intrusions on the delayed cued-recall trials, whereas the HD group showed the opposite pattern on the delayed free-recall trials. Conclusions: These new intrusion subtypes, combined with traditional memory analyses (e.g., recall versus recognition performance), promise to enhance our ability to distinguish between the memory disorders associated with primarily medial-temporal versus subcortical-frontal involvement.
Hospital environmental surfaces are frequently contaminated by microorganisms. However, the causal mechanism of bacterial contamination of the environment as a source of transmission is still debated. This prospective study was performed to characterize the nature of multidrug-resistant organism (MDRO) transmission between the environment and patients using standard microbiological and molecular techniques.
Prospective cohort study at 2 academic medical centers.
A prospective multicenter study to characterize the nature of bacterial transfer events between patients and environmental surfaces in rooms that previously housed patients with 1 of 4 ‘marker’ MDROs: methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, Clostridium difficile, and MDR Acinetobacter baumannii. Environmental and patient microbiological samples were obtained on admission into a freshly disinfected inpatient room. Repeat samples from room surfaces and patients were taken on days 3 and 7 and each week the patient stayed in the same room. The bacterial identity, antibiotic susceptibility, and molecular sequences were compared between organisms found in the environment samples and patient sources.
We enrolled 80 patient–room admissions; 9 of these patients (11.3%) were asymptomatically colonized with MDROs at study entry. Hospital room surfaces were contaminated with MDROs despite terminal disinfection in 44 cases (55%). Microbiological Bacterial Transfer events either to the patient, the environment, or both occurred in 12 patient encounters (18.5%) from the microbiologically evaluable cohort.
Microbiological Bacterial Transfer events between patients and the environment were observed in 18.5% of patient encounters and occurred early in the admission. This study suggests that research on prevention methods beyond the standard practice of room disinfection at the end of a patient’s stay is needed to better prevent acquisition of MDROs through the environment.
During the summer of 2016, the Hawaii Department of Health responded to the second-largest domestic foodborne hepatitis A virus (HAV) outbreak in the post-vaccine era. The epidemiological investigation included case finding and investigation, sequencing of RNA positive clinical specimens, product trace-back and virologic testing and sequencing of HAV RNA from the product. Additionally, an online survey open to all Hawaii residents was conducted to estimate baseline commercial food consumption. We identified 292 confirmed HAV cases, of whom 11 (4%) were possible secondary cases. Seventy-four (25%) were hospitalised and there were two deaths. Among all cases, 94% reported eating at Oahu or Kauai Island branches of Restaurant Chain A, with 86% of those cases reporting raw scallop consumption. In contrast, a food consumption survey conducted during the outbreak indicated 25% of Oahu residents patronised Restaurant Chain A in the 7 weeks before the survey. Product trace-back revealed a single distributor that supplied scallops imported from the Philippines to Restaurant Chain A. Recovery, amplification and sequence comparison of HAV recovered from scallops revealed viral sequences matching those from case-patients. Removal of product from implicated restaurants and vaccination of those potentially exposed led to the cessation of the outbreak. This outbreak further highlights the need for improved imported food safety.
Objectives: The third edition of the California Verbal Learning Test (CVLT-3) includes a new index termed List A versus Novel/Unrelated recognition discriminability (RD) on the Yes/No Recognition trial. Whereas the Total RD index incorporates false positive (FP) errors associated with all distractors (including List B and semantically related items), the new List A versus Novel/Unrelated RD index incorporates only FP errors associated with novel, semantically unrelated distractors. Thus, in minimizing levels of source and semantic interference, the List A versus Novel/Unrelated RD index may yield purer assessments of yes/no recognition memory independent of vulnerability to source memory difficulties or semantic confusion, both of which are often seen in individuals with primarily frontal-system dysfunction (e.g., early Huntington’s disease [HD]). Methods: We compared the performance of individuals with Alzheimer’s disease (AD) and HD in mild and moderate stages of dementia on CVLT-3 indices of Total RD and List A versus Novel/Unrelated RD. Results: Although AD and HD subgroups exhibited deficits on both RD indices relative to healthy comparison groups, those with HD generally outperformed those with AD, and group differences were more robust on List A versus Novel/Unrelated RD than on Total RD. Conclusions: Our findings highlight the clinical utility of the new CVLT-3 List A versus Novel/Unrelated RD index, which (a) maximally assesses yes/no recognition memory independent of source and semantic interference; and (b) provides a greater differentiation between individuals whose memory disorder is primarily at the encoding/storage level (e.g., as in AD) versus at the retrieval level (e.g., as in early HD). (JINS, 2018, 24, 833–841)
Mechanical forces during machine milking induce changes in teat condition which can be differentiated into short-term and long-term changes. Machine milking-induced short-term changes in teat condition (STC) are defined as tissue responses to a single milking and have been associated with the risk of new intramammary infection. Albeit, their association with teat characteristics, such as teat-end shape, has not been investigated by rigorous methods. The primary objective was to determine the association of STC, as measured by ultrasonography, with teat-end shape. The second objective was to describe possible differences in the recovery time of teat tissue after machine milking among teats with different teat-end shapes. Holstein cows (n=128) were enrolled in an observational study, housed in free-stall pens with sand bedding and milked three times a day. Ultrasonography of the left front and right hind teat was performed after teat preparation before milking (t−1), immediately after milking (t0) and 1, 3, 5 and 7 h after milking (t1, t3, t5, t7). The teat tissue parameters measured from ultrasound scans were teat canal length, teat-end diameter, teat-end diameter at the midpoint between the distal and proximal end of the teat canal, teat wall thickness, and teat cistern width. Teat-end shape was assessed visually and classified into three categories: pointed, flat and round. Multivariable linear regression analyses showed differences in the relative change of teat tissue parameters (compared with t−1) at t0 among teats with different teat-end shapes, with most parameters showing the largest change for round teats. The premilking values were reached (recovery time) after 7 h in teats with a pointed teat-end shape, whereas recovery time was greater than 7 h in teats with flat and round teat-end shapes. Under the same liner and milking machine conditions, teats with a round teat-end shape had the most severe short-term changes. The results of this observational study indicated that teat-end shape may be one of the factors that contribute to the severity of STC.
Extinctions have altered island ecosystems throughout the late Quaternary. Here, we review the main historic drivers of extinctions on islands, patterns in extinction chronologies between islands, and the potential for restoring ecosystems through reintroducing extirpated species. While some extinctions have been caused by climatic and environmental change, most have been caused by anthropogenic impacts. We propose a general model to describe patterns in these anthropogenic island extinctions. Hunting, habitat loss and the introduction of invasive predators accompanied prehistoric settlement and caused declines of endemic island species. Later settlement by European colonists brought further land development, a different suite of predators and new drivers, leading to more extinctions. Extinctions alter ecological networks, causing ripple effects for islands through the loss of ecosystem processes, functions and interactions between species. Reintroduction of extirpated species can help restore ecosystem function and processes, and can be guided by palaeoecology. However, reintroduction projects must also consider the cultural, social and economic needs of humans now inhabiting the islands and ensure resilience against future environmental and climate change.
Cognitive deficits are a core feature of schizophrenia, and impairments in most domains are thought to be stable over the course of the illness. However, cross-sectional evidence indicates that some areas of cognition, such as visuospatial associative memory, may be preserved in the early stages of psychosis, but become impaired in later established illness stages. This longitudinal study investigated change in visuospatial and verbal associative memory following psychosis onset.
In total 95 first-episode psychosis (FEP) patients and 63 healthy controls (HC) were assessed on neuropsychological tests at baseline, with 38 FEP and 22 HCs returning for follow-up assessment at 5–11 years. Visuospatial associative memory was assessed using the Cambridge Neuropsychological Test Automated Battery Visuospatial Paired-Associate Learning task, and verbal associative memory was assessed using Verbal Paired Associates subtest of the Wechsler Memory Scale - Revised.
Visuospatial and verbal associative memory at baseline did not differ significantly between FEP patients and HCs. However, over follow-up, visuospatial associative memory deteriorated significantly for the FEP group, relative to healthy individuals. Conversely, verbal associative memory improved to a similar degree observed in HCs. In the FEP cohort, visuospatial (but not verbal) associative memory ability at baseline was associated with functional outcome at follow-up.
Areas of cognition that develop prior to psychosis onset, such as visuospatial and verbal associative memory, may be preserved early in the illness. Later deterioration in visuospatial memory ability may relate to progressive structural and functional brain abnormalities that occurs following psychosis onset.
As a pilot study to investigate whether personalized medicine approaches could have value for the reduction of malaria-related mortality in young children, we evaluated questionnaire and biomarker data collected from the Mother Offspring Malaria Study Project birth cohort (Muheza, Tanzania, 2002–2006) at the time of delivery as potential prognostic markers for pediatric severe malarial anemia. Severe malarial anemia, defined here as a Plasmodium falciparum infection accompanied by hemoglobin levels below 50 g/L, is a key manifestation of life-threatening malaria in high transmission regions. For this study sample, a prediction model incorporating cord blood levels of interleukin-1β provided the strongest discrimination of severe malarial anemia risk with a C-index of 0.77 (95% CI 0.70–0.84), whereas a pragmatic model based on sex, gravidity, transmission season at delivery, and bed net possession yielded a more modest C-index of 0.63 (95% CI 0.54–0.71). Although additional studies, ideally incorporating larger sample sizes and higher event per predictor ratios, are needed to externally validate these prediction models, the findings provide proof of concept that risk score-based screening programs could be developed to avert severe malaria cases in early childhood.
Cannabis use shows a robust dose-dependent relationship with psychosis risk among the general population. Despite this, it has been difficult to link cannabis use with risk for transitioning to a psychotic disorder among individuals at ultra-high risk (UHR) for psychosis. The present study examined UHR transition risk as a function of cannabis use characteristics which vary substantially between individuals including age of first use, cannabis abuse severity and a history of cannabis-induced attenuated psychotic symptoms (APS).
Participants were 190 UHR individuals (76 males) recruited at entry to treatment between 2000 and 2006. They completed a comprehensive baseline assessment including a survey of cannabis use characteristics during the period of heaviest use. Outcome was transition to a psychotic disorder, with mean time to follow-up of 5.0 years (range 2.4–8.7 years).
A history of cannabis abuse was reported in 58% of the sample. Of these, 26% reported a history of cannabis-induced APS. These individuals were 4.90 (95% confidence interval 1.93–12.44) times more likely to transition to a psychotic disorder (p = 0.001). Greater severity of cannabis abuse also predicted transition to psychosis (p = 0.036). However, this effect was mediated by higher abuse severity among individuals with a history of cannabis-induced APS.
Findings suggest that cannabis use poses risk in a subpopulation of UHR individuals who manifest cannabis-induced APS. Whether this reflects underlying genetic vulnerability requires further study. Nevertheless, findings reveal an important early marker of risk with potentially significant prognostic utility for UHR individuals.
Many of the important events in the life of a star occur, or are thought to occur, during the red giant or supergiant phase of evolution. For example, in heavy and intermediate mass stars supernova explosions terminate normal evolutionary processes while in lower mass stars the stellar envelope is entirely removed giving rise to planetary nebulae and, subsequently, white dwarfs. Theoretical calculations suggest that before the onset of these rather drastic events, a significant amount of nucleosynthesis occurs, giving rise to enhanced surface abundances of He, C, N and s-process elements (e.g., Iben and Truran 1978; Renzini and Voli 1981); loss of the envelope material by stellar winds, planetary nebula ejection and supernova explosions produce overall galactic enrichment in these elements.
A photometric survey of a central region of the LMC has been undertaken to obtain a magnitude and colour limited sample of bright asymptotic giant branch (AGB) stars; the stars were selected from V and Ic plates taken by the UK Schmidt Telescope Unit (UKSTU) at Coonabarabran. Infrared JHK photometry has been obtained for all the stars in the sample in order to determine bolometric magnitudes, and spectra have been obtained for most of the stars to obtain spectral types. Stars in the sample have bolometric magnitudes up to the AGB limit of Mbol ∼ – 7.1, and many of the stars show evidence for dredge-up of carbon and s-process elements during helium shell flashes. A bolometric luminosity function has been constructed and its behaviour is discussed in terms of possible mass loss scenarios.
Angular diameters of Magellanic Cloud planetary nebulae obtained using speckle interferometry on the AAT are presented. The mass of ionized gas in each nebula is derived from the angular diameter and published Hβ line fluxes; the derived masses range from 0.005M⊙ to 0.19M⊙, with a mean value of 0.08M⊙. All the planetary nebulae observed are relatively small (diameter ≲0.13pc), young (age ≲ 2500 years), bright and dense. They are therefore almost certainly only partially ionized, so that the masses derived for the ionized parts of the nebula are lower limits to the total nebula mass.