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The existence of a frontotemporal dementia phenocopy (phFTD) syndrome remains controversial. Opinions differ on whether the phenocopy presentation represents the neuropsychological manifestation of a mid-life decompensation in vulnerable pre-morbid personalities or an indolent prodrome of behavioral-variant FTD (bvFTD). Literature on this topic is sparse and clinicians and patients have little guidance around prognosis and management.
To describe the demographic, neuropsychological and biomarker profiles of a case series of phFTD patients, attending the memory clinic and review relevant literature.
Retrospective review of all cases diagnosed with phFTD.
Eleven cases were identified (male = 9, female = 2). Mean age 55.8 years. Subjective complaints comprised memory and language difficulties. Collateral reports described apathy, aggression, impulsivity, disinhibition, hyperorality. Function was relatively preserved though motivation or supervision for higher-level tasks was sometimes required. All had non-neurodegenerative MRI and PET scans. Neuropsychological test (NPT) findings predominantly showed executive dysfunction and fluency impairment. A total of 3/11 had non-amnestic memory impairment. Follow-up imaging and NPT were invariably unchanged; 1/11 had a pre-morbid psychiatric diagnosis; 5/11 had unusual personality traits pre-morbidly. Major psychosocial stressors were documented in 7/11. Management consisted of psychosocial interventions to support function and interpersonal relationships.
The literature describes the phFTD syndrome as predominantly affecting males though we include 2 females who meet the criteria. In keeping with our findings, personality traits and psychosocial stressors may be more common in phFTD than bvFTD. More severe symptoms, memory impairment at presentation and C9ORF72 gene mutation may predict eventual progression. Those who do not progress have minimal long-term functional impairment though behavioral symptoms persist.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
The transition from adolescent to adult mental health services (AMHS) is associated with disengagement, poor continuity of care and patient dissatisfaction. The aim of this retrospective and descriptive study was to describe the ‘care pathways’ in an independent mental health service when adolescents reach age 18 and to investigate the level of engagement of those who transitioned to independent AMHS.
This is a retrospective, naturalistic and descriptive study in design. All patients discharged from the St Patrick’s Adolescent Mental Health Service aged 17 years and 6 months and older, during a 3-year period between January 2014 and December 2016, were included. Electronic records were used to collect socio-demographic and clinical details and to determine engagement rates in adolescents who transferred to independent adult services.
A total of 180 patients aged over 17 years and 6 months were discharged from the adolescent service. Of these, 45.6% were discharged to their GP, 28.9% to public mental health services and 25.6% to independent mental health services. The majority who transitioned to independent AMHS went to a Young Adult Service, which had high engagement rates at 3 and 12 months post-transition.
In this independent mental health service, less than half of adolescents who reach the transition age are referred onto AMHS. Engagement rates were found to be high among those referred on to a specialised young adult service.
Major depressive disorder (MDD) is a common and disabling condition with well-established heritability and environmental risk factors. Gene–environment interaction studies in MDD have typically investigated candidate genes, though the disorder is known to be highly polygenic. This study aims to test for interaction between polygenic risk and stressful life events (SLEs) or childhood trauma (CT) in the aetiology of MDD.
The RADIANT UK sample consists of 1605 MDD cases and 1064 controls with SLE data, and a subset of 240 cases and 272 controls with CT data. Polygenic risk scores (PRS) were constructed using results from a mega-analysis on MDD by the Psychiatric Genomics Consortium. PRS and environmental factors were tested for association with case/control status and for interaction between them.
PRS significantly predicted depression, explaining 1.1% of variance in phenotype (p = 1.9 × 10−6). SLEs and CT were also associated with MDD status (p = 2.19 × 10−4 and p = 5.12 × 10−20, respectively). No interactions were found between PRS and SLEs. Significant PRSxCT interactions were found (p = 0.002), but showed an inverse association with MDD status, as cases who experienced more severe CT tended to have a lower PRS than other cases or controls. This relationship between PRS and CT was not observed in independent replication samples.
CT is a strong risk factor for MDD but may have greater effect in individuals with lower genetic liability for the disorder. Including environmental risk along with genetics is important in studying the aetiology of MDD and PRS provide a useful approach to investigating gene–environment interactions in complex traits.
Increasing rates of young people not in education, employment or training (NEETs) are a cause of concern both in Ireland and internationally, but little longitudinal research has examined the link between psychiatric disorder in young people and NEET status.
The Challenging Times (CT) Study is a longitudinal, population-based study of psychopathology among 212 young Irish people. Clinical interviews were performed at two time points: 12–15 years and 19–24 years.
NEET status in young adulthood was associated with a sevenfold increased risk of current suicidal ideation. This result was independent of prior adolescent mental disorder. NEET young people had a fourfold increased odds of being diagnosed with a mental disorder in childhood or early adolescence compared with their economically active peers. NEET young people were at an almost threefold increased risk of any mental health disorder a twofold increased risk of anxiety disorder and threefold increased odds of suicide attempts over their lifetime compared with economically active peers.
NEET young people are at increased risk for mental disorder and suicidal ideation. The association is bidirectional, as prior mental disorder in adolescence appeared to account for much of the association between NEET status and current mental health problems. However, economic inactivity conveys an increased risk for suicidal ideation over and above that due to prior disorder. Our findings provide a compelling economic and societal argument for early intervention and treatment of mental disorder and the importance of vocational interventions for reducing suicide risk in young adults.
Strategies to dissect phenotypic and genetic heterogeneity of major depressive disorder (MDD) have mainly relied on subphenotypes, such as age at onset (AAO) and recurrence/episodicity. Yet, evidence on whether these subphenotypes are familial or heritable is scarce. The aims of this study are to investigate the familiality of AAO and episode frequency in MDD and to assess the proportion of their variance explained by common single nucleotide polymorphisms (SNP heritability).
For investigating familiality, we used 691 families with 2–5 full siblings with recurrent MDD from the DeNt study. We fitted (square root) AAO and episode count in a linear and a negative binomial mixed model, respectively, with family as random effect and adjusting for sex, age and center. The strength of familiality was assessed with intraclass correlation coefficients (ICC). For estimating SNP heritabilities, we used 3468 unrelated MDD cases from the RADIANT and GSK Munich studies. After similarly adjusting for covariates, derived residuals were used with the GREML method in GCTA (genome-wide complex trait analysis) software.
Significant familial clustering was found for both AAO (ICC = 0.28) and episodicity (ICC = 0.07). We calculated from respective ICC estimates the maximal additive heritability of AAO (0.56) and episodicity (0.15). SNP heritability of AAO was 0.17 (p = 0.04); analysis was underpowered for calculating SNP heritability of episodicity.
AAO and episodicity aggregate in families to a moderate and small degree, respectively. AAO is under stronger additive genetic control than episodicity. Larger samples are needed to calculate the SNP heritability of episodicity. The described statistical framework could be useful in future analyses.
The future of centimetre and metre-wave astronomy lies with the Square Kilometre Array (SKA), a telescope under development by a consortium of 17 countries that will be 50 times more sensitive than any existing radio facility. Most of the key science for the SKA will be addressed through large-area imaging of the Universe at frequencies from a few hundred MHz to a few GHz. The Australian SKA Pathfinder (ASKAP) is a technology demonstrator aimed in the mid-frequency range, and achieves instantaneous wide-area imaging through the development and deployment of phased-array feed systems on parabolic reflectors. The large field-of-view makes ASKAP an unprecedented synoptic telescope that will make substantial advances in SKA key science. ASKAP will be located at the Murchison Radio Observatory in inland Western Australia, one of the most radio-quiet locations on the Earth and one of two sites selected by the international community as a potential location for the SKA. In this paper, we outline an ambitious science program for ASKAP, examining key science such as understanding the evolution, formation and population of galaxies including our own, understanding the magnetic Universe, revealing the transient radio sky and searching for gravitational waves.
Although usually thought of as external environmental stressors, a significant heritable component has been reported for measures of stressful life events (SLEs) in twin studies.
We examined the variance in SLEs captured by common genetic variants from a genome-wide association study (GWAS) of 2578 individuals. Genome-wide complex trait analysis (GCTA) was used to estimate the phenotypic variance tagged by single nucleotide polymorphisms (SNPs). We also performed a GWAS on the number of SLEs, and looked at correlations between siblings.
A significant proportion of variance in SLEs was captured by SNPs (30%, p = 0.04). When events were divided into those considered to be dependent or independent, an equal amount of variance was explained for both. This ‘heritability’ was in part confounded by personality measures of neuroticism and psychoticism. A GWAS for the total number of SLEs revealed one SNP that reached genome-wide significance (p = 4 × 10−8), although this association was not replicated in separate samples. Using available sibling data for 744 individuals, we also found a significant positive correlation of R2 = 0.08 in SLEs (p = 0.03).
These results provide independent validation from molecular data for the heritability of reporting environmental measures, and show that this heritability is in part due to both common variants and the confounding effect of personality.
This paper seeks to examine the feasibility of targeting cognitive therapy
during early relapse, using a single case design. Gumley, White and Power
(1999) offer a theoretical conceptualization of psychotic relapse based on
Teasdale and Barnard's (1993) ICS model of depression. This
conceptualization aims to provide a means for clinicians and patients to
formulate the key psychological factors, which may be responsible for the
initiation, acceleration and maintenance of relapse, thereby enabling these
factors to be targeted should a relapse be indicated. The intervention
received by a case illustrated in this paper is derived from the ICS
conceptualization of relapse. The intervention has two stages: an initial
engagement and formulation phase and, if required, a targeted cognitive
therapy phase. All of the characteristics of traditional cognitive therapy
are adhered to, including the use of structure, problem focus, agenda, a
socratic style, and collaboration. The paper concludes that there is a need
for further research to provide further evidence of the feasibility and
efficacy of this approach.
Sand quarrying in 1989 at Sand Fiold, Sandwick, in Orkney resulted in the accidental discovery of a rock-cut chamber containing a cist. Subsequent excavation revealed that this cist had a number of unusual features. The cist slabs had been fitted together exceptionally well and the completed cist was designed to be re-opened by the removal of a side slab. Within the chamber, access was provided to the opening side of the cist and a relieving structure was built over its capstone.
The cist contained cremation and inhumation burials that had been inserted on more than one occasion; as its builders intended. A collection of poorly preserved unburnt bone was found to comprise the remains of two individuals: a young adult and a foetus. Two collections of cremated bone, each derived from a single adult, were also present; one in a Food Vessel Urn, the second forming a pile on the floor and containing two burnt antler tines and two unburnt human teeth. The un-urned cremation deposit and the unburnt bones had been covered in mats of plant fibres derived from grass and sedge. The urn had been lined with basketry, also made from grass. Outside the cist, an exceptionally large collection of fuel ash slag (FAS), derived from a cremation pyre, had been deposited between the cist and the wall of the rock-cut chamber.
Radiocarbon dates indicate that the site and its contents had a long history. The FAS and the foetus skeleton date to 2900–2500 cal BC. Between 2200 and 1900 cal BC the urned cremation and young adult human bones were inserted and charcoal was deposited in the foundation slots for the back wall of the cist. The deposition of the un-urned cremation was dated to 1000–800 cal BC, some 900 years later, when the urn had already fallen over and broken. At this time, it is assumed that the urn was restored to an upright position and propped with stones, while the stone lid for the urn was reused in the foundation slot of the left-hand side of the cist. Reuse and refurbishment over two millennia seem evidenced in the results from this cist.
We have studied the effect of clonidine on gastric motility, by examining the effect on gastric emptying of indigestible solids. In Wistar rats, either clonidine or saline was injected intraperitoneally, and ten steel balls (1.0mm in diameter) were inserted into the stomach. Gastric emptying was examined at 3 h. Clonidine delayed gastric emptying of steel balls (ED50 = 0.0071 [95% confidence interval: 0.0033–0.013) mg kg−1). Yohimbine, but not naloxone, significantly antagonized the inhibitory effect of clonidine. We conclude that clonidine inhibits gastric motility through the alpha2 adrenoceptor.
The hypothermic, growth hormone and corticotrophin (ACTH) responses to the 5-HT1A receptor agonist buspirone (30 mg orally) were measured in 20 unmedicated patients with major depression and 20 healthy controls. Compared with the controls, the hypothermic responses of the depressed patients to buspirone were significantly attenuated, particularly in patients with melancholic depression. In contrast, the responses of growth hormone and ACTH to buspirone were unchanged. The data suggest that major depression may be associated with impaired sensitivity of 5-HT1A autoreceptors but that the function of the post-synaptic 5-HT1A receptors that mediate growth hormone and ACTH release is unaltered. Within the limitations that attend the use of buspirone as a 5-HT1A probe, our data suggest that the decrement in serotonin neurotransmission at post-synaptic 5-HT1A receptors in depression is due to decreased serotonin release rather than impaired responsivity of post-synaptic 5-HT1A receptors.
Evidence indicates a strong positive relationship between increases in nitrogen fertilizer use on cropland and nitrate concentrations in shallow ground water. This raises concern about the fate and efficiency of nitrogen fertilizer with current farming practices. Approximately 50 percent of the nitrogen fertilizer applied may be recovered by agronomic crops and 35 percent or less removed in the harvested grain of a crop such as corn. The residual nitrogen is subject to loss by several processes, one being leaching from the crop root zone. Alternative production systems that provide ground water protection must give attention to improved management of nitrogen fertilizer and to practices that minimize the need for nitrogen fertilizer and reduce soil nitrate concentrations. Most important in nitrogen fertilizer management is to more closely match nitrogen availability in the soil with crop needs and to avoid over-fertilization. Nitrogen fertilizer use can be reduced by alternate cropping of low and high nitrogen-demanding crops, use of legumes in the crop rotation to fix nitrogen, and proper use of manures, crop residues, and other organic wastes. Residual nitrates in soil can be reduced by use of cover crops, nitrogen-scavenging crops in the rotation, and alternating shallow and deep-rooted crops. Conservation tillage alone as used with many conventional cropping systems will probably not change the current status of nitrate leaching. Practices used by organic farmers should be carefully studied as possible approaches for ground water protection and adaptation into conservation tillage systems for conserving soil and water resources.
1. Erythrocytes (RBC) from control and marginally riboflavin-deficient subjects were fractionated into nine fractions using a discrete density gradient.
2. Glutathione reductase (NAD(P)H: glutathione oxidoreductase; EC 18.104.22.168) activity and aspartate aminotransferase (EC 22.214.171.124) activity (with and without the appropriate co-enzymes) reduced glutathione, methaemoglobin, sulphaemoglobin and oxyhaemoglobin and susceptibility to peroxide were measured in RBC in the different fractions.
3. Glutathione reductase and aspartate aminotransferase activities and concentrations of reduced glutathione and oxyhaemoglobin all declined with age, while melhaemoglobin, sulphaemoglobin and susceptibility to peroxide increased with age.
4. The only significant differences noted in the RBC from marginally-riboflavin-deficient subjects by comparison with controls, were lower glutathione reductase activities and higher concentrations of methaemoglobin.
5. The role of riboflavin in those sytems controlling RBC integrity is discussed.
The fine round barrow described below was the second of two excavated on behalf of the Ministry of Public Building and Works during the summer of 1961. The site, which is on Upper Chalk with Flint, is the eastern outlier of a linear barrow cemetery on Earl's Farm Down, and lies at 400 feet on the western slope of Beacon Hill (fig. 1) south of the main Amesbury-Andover road (O.S. National Grid: SU/184419, Sheet 167).
The problem of causality in non-relativistic scattering where a bounded region of non-linear interaction occurs is re-examined in the context of a paper by Ebel. In the model considered it is shown that the acausal behaviour cannot be accounted for in the straightforward manner that is possible for an energy-dependent but linear potential which gives rise to a similar R-matrix.