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Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Sample preparation techniques for radiocarbon analysis of dissolved inorganic carbon (DIC) and dissolved organic carbon (DOC) in freshwater, as well as CO2 and CH4 in gas mixtures are presented. Focused efforts have been on developing a robust and low-background wet oxidation extraction method for DOC in freshwater, following routine methods developed for stable carbon isotope analysis and adapted for radiocarbon (14C) analysis. DIC (by acidification) and DOC (by wet oxidation) are converted to CO2 in pre-baked septum-fitted borosilicate bottles, where the resulting CO2 is extracted from the dissolved and headspace portions on a low-flow He-carrier flow-through system interfaced to a vacuum extraction line. A peripheral CH4 extraction line interfaces to the flow line to separate CH4 from environmental samples following the methods of Pack et al. 2015. High sample throughput and low blanks are achievable with this method. DIC and DOC blanks are consistently <0.7 pMC, while CO2 and CH4 blanks are typically <0.1 pMC.
The impact of losing a limb in military service extends well beyond initial recovery and rehabilitation, with long-term consequences and challenges requiring health-care commitments across the lifecourse. This paper presents a systematic review of the current state of knowledge regarding the long-term impact of ageing and limb-loss in military veterans. Key databases were systematically searched including: ASSIA, CINAHL, Cochrane Library, Medline, Web of Science, PsycArticles/PsychInfo, ProQuest Psychology and ProQuest Sociology Journals, and SPORTSDiscus. Empirical studies which focused on the long-term impact of limb-loss and/or health-care requirements in veterans were included. The search process revealed 30 papers relevant for inclusion. These papers focused broadly on four themes: (a) long-term health outcomes, prosthetics use and quality of life; (b) long-term psycho-social adaptation and coping with limb-loss; (c) disability and identity; and (d) estimating the long-term costs of care and prosthetic provision. Findings present a compelling case for ensuring the long-term care needs and costs of rehabilitation for older limbless veterans are met. A dearth of information on the lived experience of limb-loss and the needs of veterans’ families calls for further research to address these important issues.
The A.E. Lalonde accelerator mass spectrometer (3MV, HVEE) was commissioned in early 2014 at the University of Ottawa (Canada). The radiocarbon sample preparation laboratory spent the better part of 2014 undertaking a quality control program, establishing pretreatment protocols, and streamlining sample processing. In the fall of 2014, the first unknown samples were accepted and in the first year of operation well over 1000 targets (~60% unknowns) were analyzed. Here, we present an overview of sample processing protocols and results from routinely measured standards, reference, and blank materials.
Repetitive transcranial magnetic stimulation (rTMS) has been shown to be an effective treatment for depression. However, there has been little research to determine optimal parameters for treatment.
This study compared two rTMS treatment regimes for the treatment of major depression. Seventy-seven participants were randomized to either spaced or daily treatment. Spaced rTMS was given 3 days/week for 6 weeks (18 treatments in total) and daily rTMS was given 5 days/week for 4 weeks (20 treatments in total). All participants were assessed at baseline and after 4 weeks of treatment. Participants in the spaced treatment group were also assessed after 6 weeks of treatment. All participants were treated at 110% of the resting motor threshold with high-frequency rTMS (10 Hz) to the left dorsolateral prefrontal cortex (DLPFC) followed by low-frequency rTMS to the right DLPFC.
Participants in the daily treatment group showed more improvement by week 4 than those in the spaced treatment group; however, both groups had similar improvement by treatment completion. There was significant improvement in both groups in ratings of depression and anxiety, with no significant differences between groups.
Our study indicates that the efficacy of rTMS is related to the number of treatments given and that spacing the treatments neither improves nor reduces efficacy.
It has been suggested that people with psychopathic disorders lack
empathy because they have deficits in processing distress cues (e.g.
fearful facial expressions).
To investigate brain function when individuals with psychopathy and a
control group process facial emotion.
Using event-related functional magnetic resonance imaging we compared six
people scoring ⩾25 on the Hare Psychopathy Checklist–Revised and nine
non-psychopathic healthy volunteers during an implicit emotion processing
task using fearful, happy and neutral faces.
The psychopathy group showed significantly less activation than the
control group in fusiform and extrastriate cortices when processing both
facial emotions. However, emotion type affected response pattern. Both
groups increased fusiform and extrastriate cortex activation when
processing happy faces compared with neutral faces, but this increase was
significantly smaller in the psychopathy group. In contrast, when
processing fearful faces compared with neutral faces, the control group
showed increased activation but the psychopathy group decreased
activation in the fusiform gyrus.
People with psychopathy have biological differences from controls when
processing facial emotion, and the pattern of response differs according
to emotion type.
Background: Despite its inhibitory control requirements, antisaccade
deficits have been consistently associated with working memory impairments
in schizophrenia. We investigated whether variance in antisaccade
performance could be better accounted for in terms of a specific
inhibitory function. Method: We assessed 48 clinically stable out-patients
with schizophrenia on an antisaccade task, as well as on measures of
spatial and verbal working memory, sustained selective attention, and a
simple motoric go/no-go measure of response inhibition. Results: In a
stepwise multiple regression analysis, go/no-go task performance
accounted for a considerably greater percentage of variance in antisaccade
performance (25.3%) than either working memory (8.4%) or sustained
selective attention task (9.1%). Discussion: We conclude that antisaccade
deficits in schizophrenia appear to be better understood in terms of a
specific deficit of inhibitory control than in terms of more general
difficulties with context maintenance or goal neglect. (JINS,
2006, 12, 901–906.)
Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene–nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient–genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries.
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