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C-reactive protein (CRP) is a candidate biomarker for major depressive disorder (MDD), but it is unclear how peripheral CRP levels relate to the heterogeneous clinical phenotypes of the disorder.
To explore CRP in MDD and its phenotypic associations.
We recruited 102 treatment-resistant patients with MDD currently experiencing depression, 48 treatment-responsive patients with MDD not currently experiencing depression, 48 patients with depression who were not receiving medication and 54 healthy volunteers. High-sensitivity CRP in peripheral venous blood, body mass index (BMI) and questionnaire assessments of depression, anxiety and childhood trauma were measured. Group differences in CRP were estimated, and partial least squares (PLS) analysis explored the relationships between CRP and specific clinical phenotypes.
Compared with healthy volunteers, BMI-corrected CRP was significantly elevated in the treatment-resistant group (P = 0.007; Cohen's d = 0.47); but not significantly so in the treatment-responsive (d = 0.29) and untreated (d = 0.18) groups. PLS yielded an optimal two-factor solution that accounted for 34.7% of variation in clinical measures and for 36.0% of variation in CRP. Clinical phenotypes most strongly associated with CRP and heavily weighted on the first PLS component were vegetative depressive symptoms, BMI, state anxiety and feeling unloved as a child or wishing for a different childhood.
CRP was elevated in patients with MDD, and more so in treatment-resistant patients. Other phenotypes associated with elevated CRP included childhood adversity and specific depressive and anxious symptoms. We suggest that patients with MDD stratified for proinflammatory biomarkers, like CRP, have a distinctive clinical profile that might be responsive to second-line treatment with anti-inflammatory drugs.
Declaration of interest
S.R.C. consults for Cambridge Cognition and Shire; and his input in this project was funded by a Wellcome Trust Clinical Fellowship (110049/Z/15/Z). E.T.B. is employed half time by the University of Cambridge and half time by GlaxoSmithKline; he holds stock in GlaxoSmithKline. In the past 3 years, P.J.C. has served on an advisory board for Lundbeck. N.A.H. consults for GlaxoSmithKline. P.d.B., D.N.C.J. and W.C.D. are employees of Janssen Research & Development, LLC., of Johnson & Johnson, and hold stock in Johnson & Johnson. The other authors report no financial disclosures or potential conflicts of interest.
The concepts of impulsivity and compulsivity are commonly used in psychiatry. Little is known about whether different manifest measures of impulsivity and compulsivity (behavior, personality, and cognition) map onto underlying latent traits; and if so, their inter-relationship.
A total of 576 adults were recruited using media advertisements. Psychopathological, personality, and cognitive measures of impulsivity and compulsivity were completed. Confirmatory factor analysis was used to identify the optimal model.
The data were best explained by a two-factor model, corresponding to latent traits of impulsivity and compulsivity, respectively, which were positively correlated with each other. This model was statistically superior to the alternative models of their being one underlying factor (‘disinhibition’) or two anticorrelated factors. Higher scores on the impulsive and compulsive latent factors were each significantly associated with worse quality of life (both p < 0.0001).
This study supports the existence of latent functionally impairing dimensional forms of impulsivity and compulsivity, which are positively correlated. Future work should examine the neurobiological and neurochemical underpinnings of these latent traits; and explore whether they can be used as candidate treatment targets. The findings have implications for diagnostic classification systems, suggesting that combining categorical and dimensional approaches may be valuable and clinically relevant.
To examine a library-based approach to addressing food insecurity through a child and adult summer meal programme. The study examines: (i) risk of household food insecurity among participants; (ii) perspectives on the library meal programme; and (iii) barriers to utilizing other community food resources.
Quantitative surveys with adult participants and qualitative semi-structured interviews with a sub-sample of adult participants.
Ten libraries using public and private funding to serve meals to children and adults for six to eight weeks in low-income Silicon Valley communities (California, USA) during summer 2015.
Adult survey participants (≥18 years) were recruited to obtain maximum capture, while a sub-sample of interview participants was recruited through maximum variation purposeful sampling.
Survey participants (n 161) were largely Latino (71 %) and Asian (23 %). Forty-one per cent of participants screened positive for risk of food insecurity in the past 12 months. A sub-sample of programme participants engaged in qualitative interviews (n 67). Interviewees reported appreciating the library’s child enrichment programmes, resources, and open and welcoming atmosphere. Provision of adult meals was described as building community among library patrons, neighbours and staff. Participants emphasized lack of awareness, misinformation about programmes, structural barriers (i.e. transportation), immigration fears and stigma as barriers to utilizing community food resources.
Food insecurity remains high in our study population. Public libraries are ideal locations for community-based meal programmes due to their welcoming and stigma-free environment. Libraries are well positioned to link individuals to other social services given their reputation as trusted community organizations.
Following precipitous population declines as a result of intensive hunting and 20th century predator-control programmes, hybridization of the Critically Endangered red wolf Canis rufus with coyotes Canis latrans posed a significant challenge for red wolf recovery efforts. Anthropogenic mortality and hybridization continue to pose challenges; the increasing number of wolf deaths caused by humans has limited wolf population growth, facilitated the encroachment of coyotes into eastern North Carolina, and affected the formation and disbandment of breeding pairs. We assessed the effects of anthropogenic mortality on Canis breeding units during a 22-year period (1991–2013). Our results show that deaths caused by people accounted for 40.6% of breeding pair disbandment, and gunshots were the primary cause of mortality. Red wolves replaced congeneric breeding pairs > 75% of the time when pairs disbanded under natural conditions or as a result of management actions. Since the mid 2000s anthropogenic mortality has caused annual preservation rates of red wolf breeding pairs to decline by 34%, and replacement of Canis breeders by red wolves to decline by 30%. Our results demonstrate that human-caused mortality, specifically by gunshots, had a strong negative effect on the longevity of red wolf pairs, which may benefit coyotes indirectly by removing their primary competitor. Coyotes are exacerbating the decline of red wolves by pair-bonding with resident wolves whose mates have been killed.
Intentional mummification is a practice usually associated with early Egyptian or Peruvian societies, but new evidence suggests that it may also have been widespread in prehistoric Britain, and possibly in Europe more generally. Following the discovery of mummified Bronze Age skeletons at the site of Cladh Hallan in the Western Isles of Scotland, a method of analysis has been developed that can consistently identify previously mummified skeletons. The results demonstrate that Bronze Age populations throughout Britain practised mummification on a proportion of their dead, although the criteria for selection are not yet certain.
On 30 May 2012, Surrey and Sussex Health Protection Unit was called by five nurseries reporting children and staff with sudden onset vomiting approximately an hour after finishing their lunch that day. Over the following 24 h 50 further nurseries supplied by the same company reported cases of vomiting (182 children, 18 staff affected). Epidemiological investigations were undertaken in order to identify the cause of the outbreak and prevent further cases. Investigations demonstrated a nursery-level attack rate of 55 out of 87 nurseries (63·2%, 95% confidence interval 52·2–73·3). Microbiological tests confirmed the presence of Bacillus cereus in food and environmental samples from the catering company and one nursery. This was considered microbiologically and epidemiologically consistent with toxin from this bacterium causing the outbreak. Laboratory investigations showed that the conditions used by the caterer for soaking of pearl haricot beans (known as navy bean in the USA) used in one of the foods supplied to the nurseries prior to cooking, was likely to have provided sufficient growth and toxin production of B. cereus to cause illness. This large outbreak demonstrates the need for careful temperature control in food preparation.
Impulsivity and compulsivity represent useful conceptualizations that involve dissociable cognitive functions, which are mediated by neuroanatomically and neurochemically distinct components of cortico-subcortical circuitry. The constructs were historically viewed as diametrically opposed, with impulsivity being associated with risk-seeking and compulsivity with harm-avoidance. However, they are increasingly recognized to be linked by shared neuropsychological mechanisms involving dysfunctional inhibition of thoughts and behaviors. In this article, we selectively review new developments in the investigation of the neurocognition of impulsivity and compulsivity in humans, in order to advance our understanding of the pathophysiology of impulsive, compulsive, and addictive disorders and indicate new directions for research.
As a behavioral addiction with clinical and phenomenological similarities to substance addiction, recreational and pathological gambling represent models for studying the neurobiology of addiction, without the confounding deleterious brain effects which may occur from chronic substance abuse.
A community sample of individuals aged 18–65 years who gamble was solicited through newspaper advertising. Subjects were grouped a priori into three groups (no-risk, at-risk, and pathological gamblers) based on a diagnostic interview. All subjects underwent a psychiatric clinical interview and neurocognitive tests assessing motor impulsivity and cognitive flexibility. Subjects with a current axis I disorder, history of brain injury/trauma, or implementation or dose changes of psychoactive medication within 6 weeks of study enrollment were excluded.
A total of 135 no-risk, 69 at-risk and 46 pathological gambling subjects were assessed. Pathological gamblers were significantly older, and exhibited significant deficiencies in motor impulse control (stop-signal reaction times), response speed (median ‘go’ trial response latency) and cognitive flexibility [total intra-dimensional/extra-dimensional (IDED) errors] versus controls. The finding of impaired impulse control and cognitive flexibility was robust in an age-matched subgroup analysis of pathological gamblers. The no-risk and at-risk gambling groups did not significantly differ from each other on task performance.
Impaired response inhibition and cognitive flexibility exist in people with pathological gambling compared with no-risk and at-risk gamblers. The early identification of such illness in adolescence or young adulthood may aid in the prevention of addiction onset of such disabling disorders.
Impairments in working memory are present in many psychiatric illnesses such as attention-deficit hyperactivity disorder (ADHD) and schizophrenia. The dopamine transporter and catechol-O-methyltransferase (COMT) are proteins involved in dopamine clearance and the dopamine system is implicated in the modulation of working memory (WM) processes and neurochemical models of psychiatric diseases. The effects of functional polymorphisms of the dopamine transporter gene (DAT1) and the COMT gene were investigated using a visuospatial and numerical n-back working memory paradigm. Our n-back task was designed to reflect WM alone, and made no demands on higher executive functioning.
A total of 291 healthy volunteers (aged 18–45 years) were genotyped and matched for age, sex, and Barratt Impulsivity Scale (BIS) and National Adult Reading Test (NART) scores. To assess individual gene effects on WM, factorial mixed model analysis of variances (ANOVAs) were conducted with the between-subjects factor as genotype and difficulty level (0-, 1-, 2- and 3-back) entered as the within-subjects factor.
The analysis revealed that the DAT1 or COMT genotype alone or in combination did not predict performance on the n-back task in our sample of healthy volunteers.
Behavioral effects of DAT1 and COMT polymorphisms on WM in healthy volunteers may be non-existent, or too subtle to identify without exceedingly large sample sizes. It is proposed that neuroimaging may provide more powerful means of elucidating the modulatory influences of these polymorphisms.
Antibody to cytomegalovirus (CMV) was sought in sera from Malta using immunofluorescence. Seven per cent of the infants, 36% of the school children, increasing to 100% of the adults aged over 40 years were found to have antibody. Most infection occurred in pre-school children and adults over 25 years of age. This pattern of antibody acquisition appears different from that described for other countries.
Using a 337 μm gas maser (Gebbie, Stone & Findlay 1965; Gebbie, Stone, Slough, Chamberlain & Sheraton 1966) it is possible to obtain precise measurements of the submillimetre absorption and phase shift occurring in specimens of each of the phases of matter and results have already been reported for the soild, liquid and gaseous states (Chamberlain & Gebbie 1965; Gebbie, Stone, Findlay & Pyatt 1965; Chamberlain, Werner, Gebbie & Slough 1967;, Chamberlain, Findlay & Gebbie 1965).
Trichotillomania (repetitive hair-pulling) is an Axis I psychiatric disorder whose neurobiological basis is incompletely understood. Whole-brain trichotillomania neuroimaging studies are lacking.
To investigate grey and white matter abnormalities over the whole brain in patients with trichotillomania.
Eighteen patients with DSM–IV trichotillomania and 19 healthy controls undertook structural magnetic resonance imaging after providing written informed consent. Differences in grey and white matter were investigated using computational morphometry.
Patients with trichotillomania showed increased grey matter densities in the left striatum, left amygdalo-hippocampal formation, and multiple (including cingulate, supplementary motor, and frontal) cortical regions bilaterally.
Trichotillomania was associated with structural grey matter changes in neural circuitry implicated in habit learning, cognition and affect regulation. These findings inform animal models of the disorder and highlight key regions of interest for future translational research.
A key question for the implementation of marker-assisted selection (MAS) using markers in linkage disequilibrium with quantitative trait loci (QTLs) is how many markers surrounding each QTL should be used to ensure the marker or marker haplotypes are in sufficient linkage disequilibrium (LD) with the QTL. In this paper we compare the accuracy of MAS using either single markers or marker haplotypes in an Angus cattle data set consisting of 9323 genome-wide single nucleotide polymorphisms (SNPs) genotyped in 379 Angus cattle. The extent of LD in the data set was such that the average marker–marker r2 was 0·2 at 200 kb. The accuracy of MAS increased as the number of markers in the haplotype surrounding the QTL increased, although only when the number of markers in the haplotype was 4 or greater did the accuracy exceed that achieved when the SNP in the highest LD with the QTL was used. A large number of phenotypic records (>1000) were required to accurately estimate the effects of the haplotypes.
In this paper we report on the development of micromachined filters for operation at terahertz frequencies. SU8, a negative photodefinable epoxy, is used to define arrays of high aspect ratio rods which are subsequently sputter coated in gold to form the filter. We fabricate and test a filter with a fixed period but variable diameter along the length of the array. By moving the array in the terahertz beam we demonstrate the ability to mechanically tune specific filter characteristics from a single device.
Severe hair-pulling is characteristic of trichotillomania, an impulse control disorder not otherwise classified. Other pathological habits, including severe nail-biting and skin-picking, are also prevalent and are potentially diagnosable as stereotypic movement disorder. There is increasing awareness of the morbidity associated with these kind of habit disorders but, to date, relatively few randomized controlled trials of pharmacotherapy or psychotherapy have been undertaken. Advances in the understanding of the underlying cognitive-affective mechanisms driving stereotypies in animals and humans may ultimately lead to new approaches. An affect regulation, behavioral addiction, and cognitive control (A-B-C) approach is outlined to conceptualizing and managing these conditions.
We have found photometric indications that Interacting Eclipsing Binaries of early to mid F spectral type (and possibly A) have strong magnetic activity which would arise from convective atmospheres. Light curve solutions and periodicity studies revealing spots, magnetic breaking and magnetic cycles are presented in XZ CMi, V965 Cyg and V963 Cyg.