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Diagnosis and classification for mental disorder are in flux. This transition has downstream consequences on the nature of clinical assessment in research and treatment settings. We begin this chapter by describing the prevailing categorical rubrics, which are the predominant guide to clinical assessment worldwide. These systems, despite their popularity, suffer from serious defects, which have prompted the development of alternate frameworks for conceptualization and assessment of psychopathology. We focus the remainder of the chapter on two prominent contenders to supplement, and perhaps eventually supplant, traditional categorical models. The Hierarchical Taxonomy of Psychopathology is an empirically derived system of the phenotypic dimensions of psychopathology and the Research Domain Criteria represent a biologically oriented approach to understanding risk processes implicated in mental disorder. We describe the promise and challenges facing these two emerging systems, and we speculate about how they will shape the future of clinical assessment.
The flow and fracture behavior of ceramic and other brittle materials under the influence of contact loading is important to both component fabrication and performance. The ease of machining, severity of residual surface damage and rate of wear during subsequent service are controlled to a large degree by the character and extent of the flow zone and its influence on the fracture mode. This Investigation was undertaken to provide experimental verification of the results obtained through elastic/plastic finite element modeling cf the stress distribution and deformations introduced by static contact loading. Experimentally, X-ray double-crystal diffractometry (DCD) was applied to obtain a mapping of the distortions produced beneath a Vickers indenter, and hence to evaluate the effect of material and geometric parameters on the flow and fracture mechanisms.
Major depressive disorder (MDD) is a leading cause of disease burden worldwide, with lifetime prevalence in the United States of 17%. Here we present the results of the first prospective, large-scale, patient- and rater-blind, randomized controlled trial evaluating the clinical importance of achieving congruence between combinatorial pharmacogenomic (PGx) testing and medication selection for MDD.
1,167 outpatients diagnosed with MDD and an inadequate response to ≥1 psychotropic medications were enrolled and randomized 1:1 to a Treatment as Usual (TAU) arm or PGx-guided care arm. Combinatorial PGx testing categorized medications in three groups based on the level of gene-drug interactions: use as directed, use with caution, or use with increased caution and more frequent monitoring. Patient assessments were performed at weeks 0 (baseline), 4, 8, 12 and 24. Patients, site raters, and central raters were blinded in both arms until after week 8. In the guided-care arm, physicians had access to the combinatorial PGx test result to guide medication selection. Primary outcomes utilized the Hamilton Depression Rating Scale (HAM-D17) and included symptom improvement (percent change in HAM-D17 from baseline), response (50% decrease in HAM-D17 from baseline), and remission (HAM-D17<7) at the fully blinded week 8 time point. The durability of patient outcomes was assessed at week 24. Medications were considered congruent with PGx test results if they were in the ‘use as directed’ or ‘use with caution’ report categories while medications in the ‘use with increased caution and more frequent monitoring’ were considered incongruent. Patients who started on incongruent medications were analyzed separately according to whether they changed to congruent medications by week8.
At week 8, symptom improvement for individuals in the guided-care arm was not significantly different than TAU (27.2% versus 24.4%, p=0.11). However, individuals in the guided-care arm were more likely than those in TAU to achieve remission (15% versus 10%; p<0.01) and response (26% versus 20%; p=0.01). Remission rates, response rates, and symptom reductions continued to improve in the guided-treatment arm until the 24week time point. Congruent prescribing increased to 91% in the guided-care arm by week 8. Among patients who were taking one or more incongruent medication at baseline, those who changed to congruent medications by week 8 demonstrated significantly greater symptom improvement (p<0.01), response (p=0.04), and remission rates (p<0.01) compared to those who persisted on incongruent medications.
Combinatorial PGx testing improves short- and long-term response and remission rates for MDD compared to standard of care. In addition, prescribing congruency with PGx-guided medication recommendations is important for achieving symptom improvement, response, and remission for MDD patients.
Funding Acknowledgements: This study was supported by Assurex Health, Inc.
Six snow-pit records recovered from Siple Dome, West Antarctica, during 1994 are used to study seasonal variations in chemical (major ion and H202), isotopic (deuterium) and physical stratigraphic properties during the 1988-94 period. Comparison of δD measurements and satellite-derived brightness temperature for the Siple Dome area suggests that most seasonal SD maxima occur within ±4 weeks of each 1 January. Several other chemical species (H2O2, non-sea-salt (nss) SO42-, methanesulfonic acid and NO3-) show coeval peaks with SD, together providing an accurate method for identifying summer accumulation. Sea-salt-derived species generally peak during winter/spring, but episodic input is noted throughout some years. No reliable seasonal signal is identified in species with continental sources (nssCa2+ nss Mg2+), NH4+ or nssCl-. Visible strata such as large depth-hoar layers (>5 cm) are associated with summer accumulation and its metamorphosis, but smaller hoar layers and crusts are more difficult to interpret. A multi-parameter approach is found to provide the most accurate dating of these snow-pit records, and is used to determine annual layer thicknesses at each site Significant spatial accumulation variability exists on an annual basis, but mean accumulation in the sampled 10 km2 grid for the 1988-94 period is fairly uniform.
We have used ground-based radio-echo sounding (RES) profiles to reveal the spatial distribution of basal and internal ice properties across Siple Dome, West Antarctica, and under the dormant ice streams on its flanks. The RES-detected bed-reflection power, corrected for the effects of instrumentation and ice-thickness variation, is nearly constant across Siple Dome at a value suggesting spatially homogeneous basal properties of ice frozen to bedrock. Till, if present under the dome, must be thin (<0.1 m). The high basal reflectivity measured under now dormant “Siple Ice Stream” (SIS) and Ice Stream C suggests that they are underlain by either a thin (<0.05 m) water layer or a thick (>1 m) thawed or frozen till layer. The evidence that the dormant SIS is not frozen directly to underlying bedrock (but is separated by a water or till layer) is a further indication that it was once an active ice stream, and suggests that streaming motion may have ceased before the basal layer was frozen. The absence of a thick till layer beneath Siple Dome is consistent with its apparent stability as an inter-ice-stream ridge in the past and may suggest that it will remain as a stable limitation of ice-stream width in the future.
Recovery is a key goal for individuals, and services’ recovery orientation can facilitate this process. The independent mental health sector is increasingly important in Ireland, particularly in counselling and suicide prevention. We aimed to evaluate Pieta House as a recovery-oriented service through clients’ self-rated recovery; and clients’ and therapists’ evaluation of the service.
Clients completing therapy over a 3-month period were invited to complete the Recovery Assessment Scale (RAS) and the Recovery Self Assessment-Revised (RSA-R). Therapists completed the RSA-R staff version.
Response rate was 36.7% for clients (n=88), 98% for therapists (n=49). Personal recovery was endorsed by 73.8% of clients, with highest agreement for factors ‘Willingness to Ask for Help’ (84.5%), and ‘Reliance on Others’ (82.1%). A smaller number agreed with factors ‘Personal Confidence and Hope’ (61.3%) and ‘No Domination by Symptoms’ (66.6%). Clients’ and therapists’ evaluation of the service showed high levels of agreement with factors of ‘Choice’ (90.9% clients, 100% therapists); ‘Life Goals’ (84.1% clients, 98% therapists) and ‘Individually Tailored Services’ (80.6% clients, 79.6% therapists). Client involvement in service management had the lowest level of agreement (36.4% clients, 30.6% therapists). Clients’ self-rated recovery correlated with their rating of the service (correlation value 0.993, p=0.01).
Clients’ self-rated recovery and the recovery orientation of Pieta House were rated highly, with areas for improvement in service user involvement, peer support and advocacy. The correlation of personal recovery and recovery orientation of the service may merit further study.
It has been suggested that offspring of parents with bipolar disorder are at increased risk for disruptive mood dysregulation disorder (DMDD), but the specificity of this association has not been established.
We examined the specificity of DMDD to family history by comparing offspring of parents with (a) bipolar disorder, (b) major depressive disorder and (c) a control group with no mood disorders.
We established lifetime diagnosis of DMDD using the Schedule for Affective Disorders and Schizophrenia for School Aged Children for DSM-5 in 180 youth aged 6–18 years, including 58 offspring of parents with bipolar disorder, 82 offspring of parents with major depressive disorder and 40 control offspring.
Diagnostic criteria for DMDD were met in none of the offspring of parents with bipolar disorder, 6 of the offspring of parents with major depressive disorder and none of the control offspring. DMDD diagnosis was significantly associated with family history of major depressive disorder.
Our results suggest that DMDD is not specifically associated with a family history of bipolar disorder and may be associated with parental depression.
The mechanical response of snowpacks to penetrating liquid water was observed over two winter seasons in the central Cascade Mountains, Washington, U.S.A. Following the onset of rain, three evolutionary regimes of snow behavior were identified: immediate avalanching, delayed avalanching, and return to stability. Immediate avalanching occurred within minutes to an hour after the onset of rain and the time of release could be predicted with an accuracy of less than an hour from meteorological forecasts of the transition from snow to rain. These avalanches usually slid on surfaces substantially deeper than the level to which water or associated thermal effects had penetrated. The mechanism by which alteration of a thin skin of surface snow can cause deep slab failure has not been identified, but several possibilities involving a redistribution of stress are discussed. Delayed avalanches released several hours after rain started. The delay varied, depending on the rate of increasing stress associated with the additional precipitation, and on the time taken for water to penetrate and weaken a potential sliding layer. It is difficult to define accurately the evolving distribution of liquid water in snow which makes it difficult to predict accurately the time of avalanching. Depth profiles of the rate of snow settlement showed that a wave of increased strain rate propagated into the snow in response to penetrating water. This type of measurement could prove useful for predicting when snow stability is reaching a critical condition. Avalanche activity was rare after continuation of rain for 15 h or more. This return to stability occurred after drainage structures had evolved and penetrated the full depth of the snowpack. Established drain channels route water away from potential sliding surfaces and are also relatively strong structures within a snowpack.
We present near-IR spectroscopy of a sample of 30 IRAS sources recently identified as late AGB stars, post-AGB stars or early PNe. The spectra obtained are centred at various wavelengths covering the molecular hydrogen v=1→0 S(1) 2.122 μm and v=2→1 S(1) 2.248 μm emission lines, the recombination lines of hydrogen Brγ 2.166 μm, Pfγ 3.741 μm and Brα 4.052 μm, and the CO[v=2→0] first overtone bandhead at 2.294 μm. As a result of these observations we have increased from 4 to 13 the total number of proto-PNe detected in H2 and we have confirmed that the onset of H2 emission takes place in the post-AGB phase. When the molecular hydrogen is fluorescence-excited the detection rate is found to be directly correlated with the evolutionary stage of the central star, rather than with the nebular morphology. In contrast, shocked-excited H2 is detected only in strongly bipolar proto-PNe, sometimes even at an early stage in the post-AGB phase. The strong correlation of shocked-excited H2 emission with bipolarity found confirms the result previously reported by Kastner et al. (1996) in evolved PNe. However, our results show that this correlation does not exist in the case of fluorescence-excited molecular hydrogen. (to be published in A&A).
To describe and discuss the portrayal of psychiatric illness in film and theatre.
A review of psychiatric literature on psychiatric illness and stigma was carried out. This was combined with a review of selected films and plays. The dramatic function of mental illness, and the manner of its portrayal, were considered in a discursive manner.
From Ancient Greek theatre to modern film, psychiatric illness has been used to exemplify “otherness”. This has frequently had connotations of danger and violence, either to others or to societal norms. Occasionally psychiatric illness is depicted as transformative, or an understandable reaction to an insane environment, and there is a trend towards more nuanced depictions of mental illness. However, the disproportionate association of mental illness with violence and danger is reflected in the public's perception of mental illness, and contributes to self-stigmatisation.
Ongoing communication between psychiatry, service users and the arts may help to challenge the stereotype of “mad, bad and dangerous to know”.
The public health burden of alcohol is unevenly distributed across the life course, with levels of use, abuse, and dependence increasing across adolescence and peaking in early adulthood. Here, we leverage this temporal patterning to search for common genetic variants predicting developmental trajectories of alcohol consumption. Comparable psychiatric evaluations measuring alcohol consumption were collected in three longitudinal community samples (N = 2,126, obs = 12,166). Consumption-repeated measurements spanning adolescence and early adulthood were analyzed using linear mixed models, estimating individual consumption trajectories, which were then tested for association with Illumina 660W-Quad genotype data (866,099 SNPs after imputation and QC). Association results were combined across samples using standard meta-analysis methods. Four meta-analysis associations satisfied our pre-determined genome-wide significance criterion (FDR < 0.1) and six others met our ‘suggestive’ criterion (FDR <0.2). Genome-wide significant associations were highly biological plausible, including associations within GABA transporter 1, SLC6A1 (solute carrier family 6, member 1), and exonic hits in LOC100129340 (mitofusin-1-like). Pathway analyses elaborated single marker results, indicating significant enriched associations to intuitive biological mechanisms, including neurotransmission, xenobiotic pharmacodynamics, and nuclear hormone receptors (NHR). These findings underscore the value of combining longitudinal behavioral data and genome-wide genotype information in order to study developmental patterns and improve statistical power in genomic studies.
Introduced accidentally from South America, deeproot sedge is rapidly expanding in a variety of habitats throughout the southeastern United States. Of particular concern is its rapid expansion, naturalization, and formation of monocultures in Texas coastal prairie, one of the most imperiled temperate ecoregions in North America. The objective of this research was to examine how deeproot sedge responds to prescribed fire, to the herbicide imazapic, and to treatment combinations of both. Combinations of prescribed fire and imazapic treatments and imazapic-only treatments effectively reduced deeproot sedge cover and frequency. However, plots exposed to dormant season fires (with no imazapic) had greater deeproot sedge cover after burn treatments were applied, indicating that coastal prairie management using only dormant season prescribed fire will not work toward reduction or management of this exotic invasive species. Although deeproot sedge cover was often reduced in fire–imazapic treatment combinations, it was still present in treatment plots. Moreover, desirable functional plant groups (i.e., native bunchgrasses) did not respond positively to the fire–imazapic treatments, but in some instances, woody plant coverage increased. Repeated, long-term approaches using integrated and coordinated efforts with multiple treatment options will be necessary to restore community structure to desired compositional levels. Such integrated approaches should be effective in reducing deeproot sedge frequency, cover, and extent to more manageable levels throughout its introduced geographic range.
Previous research supports gene–environment interactions for polymorphisms in the corticotropin hormone receptor 1 gene (CRHR1) and the serotonin transporter gene linked polymorphic region (5-HTTLPR) in predicting depression, but it has rarely considered genetic influences on stress sensitization processes, whereby early adversities (EA) increase depressive reactivity to proximal stressors later in life. The current study tested a gene–environment–environment interaction (G × E × E; specifically, gene–EA–proximal stress interaction) model of depression in a 20-year longitudinal study. Participants were assessed prospectively for EA up to age 5 and recent chronic stress and depressive symptoms at age 20 and genotyped for CRHR1 single nucleotide polymorphism rs110402 and 5-HTTLPR. EA predicted stronger associations between recent chronic stress and depression, and the effect was moderated by genes. CRHR1 A alleles and 5-HTTLPR short alleles were associated with greater stress sensitization (i.e., greater depressive reactivity to chronic stress for those also exposed to high levels of EA). The results are consistent with the notion that EA exposure results in neurobiological and cognitive–emotional consequences (e.g., altered hypothalamic–pituitary–adrenal axis functioning), leading to emotional distress in the face of recent stressors among those with certain genetic characteristics, although further research is needed to explore explanatory mechanisms.
The NIH Toolbox (NIHTB) Pattern Comparison Processing Speed Test was developed to assess processing speed within the NIHTB for the Assessment of Neurological Behavior and Function Cognition Battery (NIHTB-CB). This study highlights validation data collected in adults ages 18–85 on this measure and reports descriptive data, test–retest reliability, construct validity, and preliminary work creating a composite index of processing speed. Results indicated good test–retest reliability. There was also evidence for both convergent and discriminant validity; the Pattern Comparison Processing Speed Test demonstrated moderate significant correlations with other processing speed tests (i.e., WAIS-IV Coding, Symbol Search and Processing Speed Index), small significant correlations with measures of working memory (i.e., WAIS-IV Letter-Number Sequencing and PASAT), and non-significant correlations with a test of vocabulary comprehension (i.e., PPVT-IV). Finally, analyses comparing and combining scores on the NIHTB Pattern Comparison Processing Speed Test with other measures of simple reaction time from the NIHTB-CB indicated that a Processing Speed Composite score performed better than any test examined in isolation. The NIHTB Pattern Comparison Processing Speed Test exhibits several strengths: it is appropriate for use across the lifespan (ages, 3–85 years), it is short and easy to administer, and it has high construct validity. (JINS, 2014, 20, 1–12)