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This prospective, longitudinal study compared the frequency and pattern of mood changes between outpatients receiving usual care for bipolar disorder who were either taking or not taking antidepressants. One hundred and eighty-two patients with bipolar disorder self-reported mood and psychiatric medications for 4 months using a computerized system (ChronoRecord) and returned 22,626 days of data. One hundred and four patients took antidepressants, 78 did not. Of the antidepressants taken, 95% were selective serotonin or norepinephrine reuptake inhibitors, or second-generation antidepressants. Of the patients taking an antidepressant, 91.3% were concurrently taking a mood stabilizer. The use of antidepressants did not influence the daily rate of switching from depression to mania or the rate of rapid cycling, independent of diagnosis of bipolar I or II. The primary difference in mood pattern was the time spent normal or depressed. Patients taking antidepressants frequently remained in a subsyndromal depression. In this naturalistic study using self-reported data, patients with bipolar disorder who were taking antidepressants—overwhelmingly not tricyclics and with a concurrent mood stabilizer—did not experience an increase in the rate of switches to mania or rapid cycling compared to those not taking antidepressants. Antidepressants had little impact on the mood patterns of bipolar patients taking mood stabilizers.
Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database.
The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared.
There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups.
These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research.
Iron-rich meteorites are significantly underrepresented in collection statistics from Antarctica. This has led to a hypothesis that there is a sparse layer of iron-rich meteorites hidden below the surface of the ice, thereby explaining the apparent shortfall. As standard Antarctic meteorite collecting techniques rely upon a visual surface search approach, the need has thus arisen to develop a system that can detect iron objects under a few tens of centimetres of ice, where the expected number density is of the order one per square kilometre. To help answer this hypothesis, a large-scale pulse induction metal detector array has been constructed for deployment in Antarctica. The metal detector array is 6 m wide, able to travel at 15 km h-1 and can scan 1 km2 in ~11 hours. This paper details the construction of the metal detector system with respect to design criteria, notably the ruggedization of the system for Antarctic deployment. Some preliminary results from UK and Antarctic testing are presented. We show that the system performs as specified and should reach the pre-agreed target of the detection of a 100 g iron meteorite at 300 mm when deployed in Antarctica.
The Late Formative period immediately precedes the emergence of Tiwanaku, one of the earliest South American states, yet it is one of the most poorly understood periods in the southern Lake Titicaca Basin (Bolivia). In this article, we refine the ceramic chronology of this period with large sets of dates from eight sites, focusing on temporal inflection points in decorated ceramic styles. These points, estimated here by Bayesian models, index specific moments of change: (1) cal AD 120 (60–170, 95% probability): the first deposition of Kalasasaya red-rimmed and zonally incised styles; (2) cal AD 240 (190–340, 95% probability): a tentative estimate of the final deposition of Kalasasaya zonally incised vessels; (3) cal AD 420 (380–470, 95% probability): the final deposition of Kalasasaya red-rimmed vessels; and (4) cal AD 590 (500–660, 95% probability): the first deposition of Tiwanaku Redwares. These four modeled boundaries anchor an updated Late Formative chronology, which includes the Initial Late Formative phase, a newly identified decorative hiatus between the Middle and Late Formative periods. The models place Qeya and transitional vessels between inflection points 3 and 4 based on regionally consistent stratigraphic sequences. This more precise chronology will enable researchers to explore the trajectories of other contemporary shifts during this crucial period in Lake Titicaca Basin's prehistory.
This study exploits a new long-run data set of daily bid and offered exchange rates in spot and forward markets from 1919 to the present to analyze carry returns in fixed and floating currency regimes. We first find that outsized carry returns occur exclusively in the floating regime, being zero in the fixed regime. Second, we show that fixed-to-floating regime shifts are associated with negative returns to a carry strategy implemented only on floating currencies, robust to the inclusion of volatility risks. These shifts are typically characterized by global flight-to-safety events that represent bad times for carry traders.
Identifying routes of transmission among hospitalized patients during a healthcare-associated outbreak can be tedious, particularly among patients with complex hospital stays and multiple exposures. Data mining of the electronic health record (EHR) has the potential to rapidly identify common exposures among patients suspected of being part of an outbreak.
We retrospectively analyzed 9 hospital outbreaks that occurred during 2011–2016 and that had previously been characterized both according to transmission route and by molecular characterization of the bacterial isolates. We determined (1) the ability of data mining of the EHR to identify the correct route of transmission, (2) how early the correct route was identified during the timeline of the outbreak, and (3) how many cases in the outbreaks could have been prevented had the system been running in real time.
Correct routes were identified for all outbreaks at the second patient, except for one outbreak involving >1 transmission route that was detected at the eighth patient. Up to 40 or 34 infections (78% or 66% of possible preventable infections, respectively) could have been prevented if data mining had been implemented in real time, assuming the initiation of an effective intervention within 7 or 14 days of identification of the transmission route, respectively.
Data mining of the EHR was accurate for identifying routes of transmission among patients who were part of the outbreak. Prospective validation of this approach using routine whole-genome sequencing and data mining of the EHR for both outbreak detection and route attribution is ongoing.
The construct of self-concept lies at the core of the positive psychology revolution. Historically, as one of the cornerstone constructs in the social sciences, the approach to self-concept has been adapted to focus on how healthy individuals can thrive in life. In this chapter we differentiate between the historical unidimensional perspective of self-concept (centered on self-esteem) and the evolving multifaceted models discriminating between different aspects of self (such as specific academic, social, physical, and emotional components).
the definition of self-concept and the reason it is so important;
historical and evolving perspectives of self-concept;
general and domain-specific theoretical models with associated empirical research regarding self-concept, motivation, and performance;
the way different self-concept domains vary as a function of gender and age;
the impact of specific psychological and social traits on self-concept development;
the differentiation between multidimensional perspectives of personality and self-concept;
theoretical models of academic self-concept formation and its relation to achievement;
frame of reference effects in self-concept formation;
a construct-validity approach to self-concept enhancement interventions; and directions for further research.
Recovery of multidrug-resistant (MDR) Pseudomonas aeruginosa and Klebsiella pneumoniae from a cluster of patients in the medical intensive care unit (MICU) prompted an epidemiologic investigation for a common exposure.
Clinical and microbiologic data from MICU patients were retrospectively reviewed, MICU bronchoscopes underwent culturing and borescopy, and bronchoscope reprocessing procedures were reviewed. Bronchoscope and clinical MDR isolates epidemiologically linked to the cluster underwent molecular typing using pulsed-field gel electrophoresis (PFGE) followed by whole-genome sequencing.
Of the 33 case patients, 23 (70%) were exposed to a common bronchoscope (B1). Both MDR P. aeruginosa and K. pneumonia were recovered from the bronchoscope’s lumen, and borescopy revealed a luminal defect. Molecular testing demonstrated genetic relatedness among case patient and B1 isolates, providing strong evidence for horizontal bacterial transmission. MDR organism (MDRO) recovery in 19 patients was ultimately linked to B1 exposure, and 10 of 19 patients were classified as belonging to an MDRO pseudo-outbreak.
Surveillance of bronchoscope-derived clinical culture data was important for early detection of this outbreak, and whole-genome sequencing was important for the confirmation of findings. Visualization of bronchoscope lumens to confirm integrity should be a critical component of device reprocessing.
The emergence of callous unemotional (CU) traits, and associated externalizing behaviors, is believed to reflect underlying dysfunction in the amygdala. Studies of adults with CU traits or psychopathy have linked characteristic patterns of amygdala dysfunction to reduced amygdala volume, but studies in youths have not thus far found evidence of similar amygdala volume reductions. The current study examined the association between CU traits and amygdala volume by modeling CU traits and externalizing behavior as independent continuous variables, and explored the relative contributions of callous, uncaring, and unemotional traits.
CU traits and externalizing behavior problems were assessed in 148 youths using the Inventory of Callous Unemotional Traits (ICU) and the Child Behavior Checklist (CBCL). For a subset of participants (n = 93), high-resolution T1-weighted images were collected and volume estimates for the amygdala were extracted.
Analyses revealed that CU traits were associated with increased externalizing behaviors and decreased bilateral amygdala volume. These results were driven by the callous and uncaring sub-factors of CU traits, with unemotional traits unrelated to either externalizing behaviors or amygdala volume. Results persisted after accounting for covariation between CU traits and externalizing behaviors. Bootstrap mediation analyses indicated that CU traits mediated the relationship between reduced amygdala volume and externalizing severity.
These findings provide evidence that callous-uncaring traits account for reduced amygdala volume among youths with conduct problems. These findings provide a framework for further investigation of abnormal amygdala development as a key causal pathway for the development of callous-uncaring traits and conduct problems.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Callous–unemotional (CU) traits characterize a subgroup of youths with conduct problems who exhibit low empathy, fearlessness, and elevated externalizing behaviors. The current study examines the role of aberrant amygdala activity and functional connectivity during a socioemotional judgment task in youths with CU traits, and links these deficits to externalizing behaviors. Functional magnetic resonance imaging was used to compare neural responses in 18 healthy youths and 30 youths with conduct problems and varying levels of CU traits as they evaluated the acceptability of causing another person to experience each of several emotions, including fear. Neuroimaging analyses examined blood oxygenation level dependent responses and task-dependent functional connectivity. High-CU youths exhibited left amygdala hypoactivation relative to healthy controls and low-CU youths primarily during evaluations of causing others fear. CU traits moderated the relationship between externalizing behavior and both amygdala activity and patterns of functional connectivity. The present data suggest that CU youths' aberrant amygdala activity and connectivity affect how they make judgments about the acceptability of causing others emotional distress, and that these aberrations represent risk factors for externalizing behaviors like rule breaking and aggression. These findings suggest that reducing externalizing behaviors in high-CU youths may require interventions that influence affective sensitivity.
Symptoms of anxiety relating to Parkinson's disease (PD) occur commonly and include symptomatology associated with motor disability and complications arising from PD medication. However, there have been relatively few attempts to profile such disease-specific anxiety symptoms in PD. Consequently, anxiety in PD is underdiagnosed and undertreated. The present study characterizes PD-related anxiety symptoms to assist with the more accurate assessment and treatment of anxiety in PD.
Ninety non-demented PD patients underwent a semi-structured diagnostic assessment targeting anxiety symptoms using relevant sections of the Mini International Neuropsychiatric Interview (MINI-plus). In addition, they were assessed for the presence of 30 PD-related anxiety symptoms derived from the literature, the clinical experience of an expert panel and the PD Anxiety-Motor Complications Questionnaire (PDAMCQ). The onset of anxiety in relation to the diagnosis of PD was determined.
Frequent (>25%) PD-specific anxiety symptoms included distress, worry, fear, agitation, embarrassment, and social withdrawal due to motor symptoms and PD medication complications, and were experienced more commonly in patients meeting DSM-IV criteria for an anxiety disorder. The onset of common anxiety disorders was observed equally before and after a diagnosis of PD. Patients in a residual group of Anxiety Not Otherwise Specified had an onset of anxiety after a diagnosis of PD.
Careful characterization of PD-specific anxiety symptomatology provides a basis for conceptualizing anxiety and assists with the development of a new PD-specific measure to accurately assess anxiety in PD.
Recent studies on the rehabilitation of children with hydrocephalus have demonstrated the need for those planning such rehabilitation programmes to have a clear understanding of the neuropsychological and psychosocial aspects of this disorder. In an attempt to provide such information, the neuropsychological and psychosocial functioning of a group of 17 children with hydrocephalus between the ages of eight and fourteen years old was investigated. Performance by the sample with hydrocephalus was compared to that of a ‘normal’ control sample. Participants with hydrocephalus and control participants were matched on the variables of sex, age, years of education, and socio-economic status. Relative to control participants, the participants with hydrocephalus were impaired on measures of intellectual, attention, verbal and visual memory, and visuo-spatial abilities. Language alone was relatively preserved. The children with hydrocephalus also exhibited poorer self-esteem, fewer adaptive competencies, and more problem behaviours than the ‘normal’ controls. For the children with hydrocephalus, the relationship between their impaired intellectual abilities and their psychosocial functioning was investigated.
Callous-unemotional (CU) traits represent a significant risk factor for severe and persistent conduct problems in children and adolescents. Extensive neuroimaging research links CU traits to structural and functional abnormalities in the amygdala and ventromedial prefrontal cortex. In addition, adults with psychopathy (a disorder for which CU traits are a developmental precursor) exhibit reduced integrity in uncinate fasciculus, a white-matter (WM) tract that connects prefrontal and temporal regions. However, research in adolescents has not yet yielded similarly consistent findings.
We simultaneously modeled CU traits and externalizing behaviors as continuous traits, while controlling for age and IQ, in order to identify the unique relationship of each variable with WM microstructural integrity, assessed using diffusion tensor imaging. We used tract-based spatial statistics to evaluate fractional anisotropy, an index of WM integrity, in uncinate fasciculus and stria terminalis in 47 youths aged 10–17 years, of whom 26 exhibited conduct problems and varying levels of CU traits.
Whereas both CU traits and externalizing behaviors were negatively correlated with WM integrity in bilateral uncinate fasciculus and stria terminalis/fornix, simultaneously modeling both variables revealed that these effects were driven by CU traits; the severity of externalizing behavior was not related to WM integrity after controlling for CU traits.
These results indicate that WM abnormalities similar to those observed in adult populations with psychopathy may emerge in late childhood or early adolescence, and may be critical to understanding the social and affective deficits observed in this population.
The island of Cyprus was a major producer of copper and stood at the heart of east Mediterranean trade networks during the Late Bronze Age. It may also have been the source of the Red Lustrous Wheelmade Ware that has been found in mortuary contexts in Egypt and the Levant, and in Hittite temple assemblages in Anatolia. Neutron Activation Analysis (NAA) has enabled the source area of this special ceramic to be located in a geologically highly localised and geochemically distinctive area of western Cyprus. This discovery offers a new perspective on the spatial organisation of Cypriot economies in the production and exchange of elite goods around the eastern Mediterranean at this time.
Autism spectrum disorders (ASDs) are characterized by social impairments, including inappropriate responses to affective stimuli and nonverbal cues, which may extend to poor face-emotion recognition. However, the results of empirical studies of face-emotion recognition in individuals with ASD have yielded inconsistent findings that occlude understanding the role of face-emotion recognition deficits in the development of ASD. The goal of this meta-analysis was to address three as-yet unanswered questions. Are ASDs associated with consistent face-emotion recognition deficits? Do deficits generalize across multiple emotional expressions or are they limited to specific emotions? Do age or cognitive intelligence affect the magnitude of identified deficits? The results indicate that ASDs are associated with face-emotion recognition deficits across multiple expressions and that the magnitude of these deficits increases with age and cannot be accounted for by intelligence. These findings suggest that, whereas neurodevelopmental processes and social experience produce improvements in general face-emotion recognition abilities over time during typical development, children with ASD may experience disruptions in these processes, which suggested distributed functional impairment in the neural architecture that subserves face-emotion processing, an effect with downstream developmental consequences.
Two pregnancy cohorts were used to investigate the association between single-nucleotide polymorphisms (SNPs) in genes within the insulin-like growth factor (IGF)-axis and antenatal and postnatal growth from birth to adolescence. Longitudinal analyses were conducted in the Raine pregnancy cohort (n = 1162) using repeated measures of fetal head circumference (HC), abdominal circumference (AC) and femur length (FL) from 18 to 38 weeks gestation and eight measures of postnatal height and weight (1–17 years). Replications of significant associations up to birth were undertaken in the Generation R Study (n = 2642). Of the SNPs within the IGF-axis genes, 40% (n = 58) were associated with measures of antenatal growth (P ⩽ 0.05). The majority of these SNPs were in receptors; IGF-1R (23%; n = 34) and IGF-2R (13%; n = 9). Fifteen SNPs were associated with antenatal growth (either AC or HC or FL) in Raine (P ⩽ 0.005): five of which remained significant after adjusting for multiple testing. Four of these replicated in Generation R. Associations were identified between 38% (n = 55) of the IGF-axis SNPs and postnatal height and weight; 21% in IGF-1R (n = 31) and 9% in IGF-2R (n = 13). Twenty-six SNPs were significantly associated with both antenatal and postnatal growth; 17 with discordant effects and nine with concordant effects. Genetic variants in the IGF-axis appear to play a significant role in antenatal and postnatal growth. Further replication and new analytic methods are required in order to better understand this key metabolic pathway integrating biologic knowledge about the interaction between IGF-axis components.