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Our research group demonstrated that vitamin A restriction affected meat quality of Angus cross and Simmental steers. Therefore, the aim of this study is to highlight the genotype variations in response to dietary vitamin A levels. Commercial Angus and Simmental steers (n = 32 per breed; initial BW = 337.2 ± 5.9 kg; ~8 months of age) were fed a low-vitamin A (LVA) (1017 IU/kg DM) backgrounding diet for 95 days to reduce hepatic vitamin A stores. During finishing, steers were randomly assigned to treatments in a 2 × 2 factorial arrangement of genotype × dietary vitamin A concentration. The LVA treatment was a finishing diet with no supplemental vitamin A (723 IU vitamin A/kg DM); the control (CON) was the LVA diet plus supplementation with 2200 IU vitamin A/kg DM. Blood samples were collected at three time points throughout the study to analyze serum retinol concentration. At the completion of finishing, steers were slaughtered at a commercial abattoir. Meat characteristics assessed were intramuscular fat concentration, color, Warner-Bratzler shear force, cook loss and pH. Camera image analysis was used for determination of marbling, 12th rib back fat and longissimus muscle area (LMA). The LVA steers had lower (P < 0.001) serum retinol concentration than CON steers. The LVA treatment resulted in greater (P = 0.03) average daily gain than the CON treatment, 1.52 and 1.44 ± 0.03 kg/day, respectively; however, there was no effect of treatment on final BW, DM intake or feed efficiency. Cooking loss and yield grade were greater and LMA was smaller in LVA steers (P < 0.05). There was an interaction between breed and treatment for marbling score (P = 0.01) and percentage of carcasses grading United States Department of Agriculture (USDA) Prime (P = 0.02). For Angus steers, LVA treatment resulted in a 16% greater marbling score than CON (683 and 570 ± 40, respectively) and 27% of LVA Angus steers graded USDA Prime compared with 0% for CON. Conversely, there was no difference in marbling score or USDA Quality Grades between LVA and CON for Simmental steers. In conclusion, feeding a LVA diet during finishing increased marbling in Angus but not in Simmental steers. Reducing the vitamin A level of finishing diets fed to cattle with a high propensity to marble, such as Angus, has the potential to increase economically important traits such as marbling and quality grade without negatively impacting gain : feed or yield grade.
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.
To evaluate the efficacy and tolerability of once-daily quetiapine XR adjunctive to antidepressant therapy versus antidepressant alone in patients with MDD showing an inadequate response to antidepressant treatment (mainly SSRIs/SNRIs).
6-week, multicentre, double-blind, parallel-group study (D1448C00007). Patients were randomised to receive quetiapine XR 150mg/day (n=167), 300mg/day (n=163) or placebo (n=163) as add-on to maintained antidepressant treatment. Primary endpoint: baseline to Week 6 change in MADRS total score. Secondary variables included: baseline to Week 1 change in MADRS total score; baseline to Week 6 change in HAM-A total and psychic anxiety subscale scores. Safety assessments included AE reporting.
Mean change in MADRS total score (overall baseline mean, 28.4) from baseline to Week 6 was significant (p<0.01) for quetiapine XR 150mg/day (-15.26) and 300mg/day (-14.94) versus placebo (-12.21). Separation from placebo in MADRS total score was apparent from Week 1 for both quetiapine doses (p<0.001).
At Week 6, mean change from baseline in HAM-A total score (overall baseline mean, 20.8) was significant for quetiapine XR 150mg/day (-10.27, p<0.01) and 300mg/day (-9.70, p<0.05) versus placebo (-7.92). Mean change from baseline in HAM-A psychic anxiety subscale score (overall baseline mean, 12.83) was significant with quetiapine XR 150mg/day (-6.82, p<0.001) and 300mg/day (-6.47, p<0.01) versus placebo (-5.11).
Most common AEs (>10%) were dry mouth, somnolence, fatigue, sedation, constipation and dizziness with quetiapine XR.
In patients with MDD with an inadequate response to antidepressant treatment, adjunctive quetiapine XR 150mg/day and 300mg/day was well tolerated and effective at reducing depressive and anxiety symptoms.
Bipolar disorder is for most patients a life-long illness, associated with a recurrent, chronic course, and functional disability. Primary treatment goals are to stabilize the patient and prevent recurrence of episodes and suicide.
Although bipolar disorder has traditionally been regarded as an illness with good prognosis and most patients returning to normal functioning when a mood episode is over, several longitudinal studies suggest that the long-term outcome is less favorable than previously thought. Combinations of drugs are frequently used in clinical practice for mood stabilization, especially for those who have not responded to monotherapy. Although combination treatments are commonly administered, full interepisode recovery is not achieved in all patients, and as a consequence, bipolar disorder is one of the leading causes of disability.
Among clinicians and in international guidelines, lithium is widely considered as the ‘gold standard’ for long-term treatment. The choice of treatments is undergoing considerable change as new treatments are available, anticonvulsants and atypical antipsychotics are taking a more prominent position. However, the evidence available for the newer treatment options including the various combination treatments varies greatly.
The episodic nature of bipolar disorder requires prophylactic long-term treatment. Many previous worthwhile treatment effects of available mood stabilizing agents and psychotherapeutic interventions on major outcomes in bipolar disorder are only of moderate size and therefore require large-scale studies. Such trials to investigate longer-term outcomes are logistically challenging and expensive, and therefore only feasible within a multisite and multinational approach based on a common documentation system of the illness course.
Previous findings suggested that electrodermal hyporeactivity has a high sensitivity (up to 97%) and high raw specificity (up to 98%) for suicide.
To evaluate prevalence, sensitivity and specificity of electrodermal hyporeactivity for suicide and suicide attempt, with and without death intent and with violent method or not, in adult patients with a primary diagnosis of depression.
At each study site at least 100 patients with a primary diagnosis of depression, also in remission, will be recruited. Depressive symptomatology will be evaluated through the Montgomery-Asberg Depression Scale. Previous suicide attempts will be registered and the death intent of the worst attempt will be rated according to the first eight items of the Beck Suicide Intent Scale. The risk of suicide will be assessed according to rules and traditions at the centre. The EDOR Test (ElectroDermal Orienting Reactivity) will be performed. Two fingers are put on gold electrodes. Through headphones a moderately strong tone is presented now and then during the test. Sensors located within the electrodes are able to register the electrodermal response to those tones, measuring the skin conductance (i.e. electrodermal activity from sweat gland activity). Each patient will be followed up for one year for actions of intentional self-harm that require medical care and for suicide. The death intent will also be rated.
It is expected that the EDOR test detects a previously unknown neuropsychological dysfunction that is independent of the depressive state and can predict suicidality with a high sensitivity and specificity.
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.
Self-ratings of psychotic experiences might be biased by depressive symptoms.
Data from a large naturalistic multicentre trial on depressed inpatients (n = 488) who were assessed on a biweekly basis until discharge were analyzed. Self-rated psychotic symptoms as assessed with the 90-Item Symptom Checklist (SCL-90) were correlated with the SCL-90 total score, the SCL-90 depression score, the Beck Depression Inventory (BDI), the Hamilton Depression Rating Scale 21 item (HAMD-21) total score, the Montgomery Åsberg Depression Rating Scale (MADRS) total score and the clinician-rated paranoid-hallucinatory score of the Association for Methodology and Documentation in Psychiatry (AMDP) scale.
At discharge the SCL-90 psychosis score correlated highest with the SCL-90 depression score (0.78, P<0.001) and with the BDI total score (0.64, P<0.001). Moderate correlations were found for the MADRS (0.34, P<0.001), HAMD (0.37, P<0.001) and AMDP depression score (0.33, P<0.001). Only a weak correlation was found between the SCL-90 psychosis score and the AMDP paranoid-hallucinatory syndrome score (0.15, P<0.001). Linear regression showed that change in self-rated psychotic symptoms over the treatment course was best explained by a change in the SCL-90 depression score (P<0.001). The change in clinician-rated AMDP paranoid-hallucinatory score had lesser influence (P = 0.02).
In depressed patients self-rated psychotic symptoms correlate poorly with clinician-rated psychotic symptoms. Caution is warranted when interpreting results from epidemiological surveys using self-rated psychotic symptom questionnaires as indicators of psychotic symptoms. Depressive symptoms which are highly prevalent in the general population might influence such self-ratings.
Functional magnetic resonance imaging (fMRI) studies in schizophrenia found altered brain activation patterns during Theory of Mind (ToM) task performance in the so-called ToM-network, recently focusing on over- rather than under-activation. Even though most fMRI-studies applied tasks that might gradually activate the ToM-network, no study so far has investigated the time-course of ToM-performance. Some of the varying activation results might thus be due to time-course of performance.
Our aim was to investigate neural activation over time in schizophrenia compared with a healthy control sample.
Using a block design in fMRI, we presented a sophisticated paradigm that depicts moving geometrical shapes interacting in social patterns. 14 patients with schizophrenia and 15 healthy controls participated in the study. Functional activation patterns were investigated for the first and second half of the videos separately.
Both groups activated brain areas related to the ToM-network during performance of ToM videos as compared to a baseline condition. Most importanly, schizophrenia patients showed activation in ToM-related brain areas only in the second part, while healthy controls activated the ToM-network in the first part of the video presentation.
Results confirm recent findings of an increased activation in ToM-related brain areas in schizophrenia. Moreover, patients activated ToM-related brain areas later than healthy controls. This delay might be due to a general cognitive slowing, symptom-related inhibition of cognition-associated processes or specific delay in task processing. As this is the first study to investigate this time-course of ToM, more research is needed to classify results.
First rank symptoms (FRS) of schizophrenia have been used for decades for diagnostic purposes. In the new version of the DSM-5, the American Psychiatric Association (APA) has abolished any further reference to FRS of schizophrenia and treats them like any other “criterion A” symptom (e.g. any kind of hallucination or delusion) with regard to their diagnostic implication. The ICD-10 is currently under revision and may follow suit. In this review, we discuss central points of criticism that are directed against the continuous use of first rank symptoms (FRS) to diagnose schizophrenia.
We describe the specific circumstances in which Schneider articulated his approach to schizophrenia diagnosis and discuss the relevance of his approach today. Further, we discuss anthropological and phenomenological aspects of FRS and highlight the importance of self-disorder (as part of FRS) for the diagnosis of schizophrenia. Finally, we will conclude by suggesting that the theory and rationale behind the definition of FRS is still important for psychopathological as well as neurobiological approaches today.
Results of a pivotal meta-analysis and other studies show relatively poor sensitivity, yet relatively high specificity for FRS as diagnostic marker for schizophrenia. Several methodological issues impede a systematic assessment of the usefulness of FRS in the diagnosis of schizophrenia. However, there is good evidence that FRS may still be useful to differentiate schizophrenia from somatic causes of psychotic states. This may be particularly important in countries or situations with little access to other diagnostic tests. FRS may thus still represent a useful aid for clinicians in the diagnostic process.
In conclusion, we suggest to continue a tradition of careful clinical observation and fine-grained psychopathological assessment, including a focus on symptoms regarding self-disorders, which reflects a key aspect of psychosis. We suggest that the importance of FRS may indeed be scaled down to a degree that the occurrence of a single FRS alone should not suffice to diagnose schizophrenia, but, on the other hand, absence of FRS should be regarded as a warning sign that the diagnosis of schizophrenia or schizoaffective disorder is not warranted and requires specific care to rule out other causes, particularly neurological and other somatic disorders. With respect to the current stage of the development of ICD-11, we appreciate the fact that self-disorders are explicitly mentioned (and distinguished from delusions) in the list of mandatory symptoms but still feel that delusional perceptions and complex hallucinations as defined by Schneider should be distinguished from delusions or hallucinations of “any kind”. Finally, we encourage future research to explore the psychopathological context and the neurobiological correlates of self-disorders as a potential phenotypic trait marker of schizophrenia.
The use of Alzheimer disease medication for the treatment of dementia symptoms has shown significant benefits with regards to functional and cognitive outcomes as well as nursing home placement (NHP) and mortality. Hospitalisations in these patient groups are characterised by extended length of stays (LOS), frequent readmissions, frequent NHP and high-mortality rates. The impact of Alzheimer disease medication on the aforementioned outcomes remains still unknown. This study assessed the association of Alzheimer disease medication with outcomes of hospitalisation among patients with Alzheimer disease and other forms of dementia.
A dynamic retrospective cohort study from 2004 to 2015 was conducted which claims data from a German health insurance company. People with dementia (PWD) were identified using ICD-10 codes and diagnostic measures. The main predictor of interest was the use of Alzheimer disease medication. Hospitalisation outcomes included LOS, readmissions, NHP and mortality during and after hospitalisation across four hospitalisations. Confounding was addressed using a propensity score throughout all analyses.
A total of 1380 users of Alzheimer disease medication and 6730 non-users were identified. The use of Alzheimer disease medication was associated with significantly shorter LOS during the first hospitalisations with estimates for the second, third and fourth showed a tendency towards shorter hospital stays. In addition, current users of Alzheimer disease medication had a lower risk of hospital readmission after the first two hospitalisations. These associations were not significant for the third and fourth hospitalisations. Post-hospitalisation NHP and mortality rates also tended to be lower among current users than among non-users but differences did not reach statistical significance.
Our results indicate that Alzheimer disease medication might contribute to a reduction of the LOS and the number of readmissions in PWD.
Objectives: To describe multivariate base rates (MBRs) of low scores and reliable change (decline) scores on Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) in college athletes at baseline, as well as to assess MBR differences among demographic and medical history subpopulations. Methods: Data were reported on 15,909 participants (46.5% female) from the NCAA/DoD CARE Consortium. MBRs of ImPACT composite scores were derived using published CARE normative data and reliability metrics. MBRs of sex-corrected low scores were reported at <25th percentile (Low Average), <10th percentile (Borderline), and ≤2nd percentile (Impaired). MBRs of reliable decline scores were reported at the 75%, 90%, 95%, and 99% confidence intervals. We analyzed subgroups by sex, race, attention-deficit/hyperactivity disorder and/or learning disability (ADHD/LD), anxiety/depression, and concussion history using chi-square analyses. Results: Base rates of low scores and reliable decline scores on individual composites approximated the normative distribution. Athletes obtained ≥1 low score with frequencies of 63.4% (Low Average), 32.0% (Borderline), and 9.1% (Impaired). Athletes obtained ≥1 reliable decline score with frequencies of 66.8%, 32.2%, 18%, and 3.8%, respectively. Comparatively few athletes had low scores or reliable decline on ≥2 composite scores. Black/African American athletes and athletes with ADHD/LD had higher rates of low scores, while greater concussion history was associated with lower MBRs (p < .01). MBRs of reliable decline were not associated with demographic or medical factors. Conclusions: Clinical interpretation of low scores and reliable decline on ImPACT depends on the strictness of the low score cutoff, the reliable change criterion, and the number of scores exceeding these cutoffs. Race and ADHD influence the frequency of low scores at all cutoffs cross-sectionally.
Although accumulating evidence supports the hypothesis that immune/inflammatory mechanisms are associated with the pathophysiology of bipolar disorder (BD), data about the profile of chemokines (chemotactic cytokines) and chemokine receptors are still scarce. The current study was designed to evaluate the expression of chemokine receptors on lymphocytes of patients with BD in comparison with controls.
Thirty-three patients with type I BD (N = 21 in euthymia; N = 6 in mania/hypomania; N = 6 in depression) and 22 age- and sex-matched controls were subjected to clinical evaluation and peripheral blood draw. The expression of chemokine receptors CCR3, CCR5, CXCR4, and CXCR3 on CD4+ and CD8+ lymphocytes was assessed by flow cytometry.
Patients with BD had decreased percentage of CD4+CXCR3+ (p = 0.024), CD4+CCR3+ (p = 0.042), and CD4+CCR5+ (0.013) lymphocytes in comparison with controls. The percentage of both CD4+ and CD8+ lymphocytes expressing the chemokine receptor CXCR4 was similar in patients with BD and controls. Likewise, the percentages of CD8+CXCR3+, CD8+CCR3+, and CD8+CCR5+ lymphocytes were similar in patients with BD and controls.
Our findings reinforce the hypothesis that immune pathways, especially involving CD4+ lymphocytes, are involved in the physiopathology of BD.
A core question in the debate about how to organise mental healthcare is whether in- and out-patient treatment should be provided by the same (personal continuity) or different psychiatrists (specialisation). The controversial debate drives costly organisational changes in several European countries, which have gone in opposing directions. The existing evidence is based on small and low-quality studies which tend to favour whatever the new experimental organisation is.
We compared 1-year clinical outcomes of personal continuity and specialisation in routine care in a large scale study across five European countries.
This is a 1-year prospective natural experiment conducted in Belgium, England, Germany, Italy and Poland. In all these countries, both personal continuity and specialisation exist in routine care. Eligible patients were admitted for psychiatric in-patient treatment (18 years of age), and clinically diagnosed with a psychotic, mood or anxiety/somatisation disorder.
Outcomes were assessed 1 year after the index admission. The primary outcome was re-hospitalisation and analysed for the full sample and subgroups defined by country, and different socio-demographic and clinical criteria. Secondary outcomes were total number of inpatient days, involuntary re-admissions, adverse events and patients’ social situation. Outcomes were compared through mixed regression models in intention-to-treat analyses. The study is registered (ISRCTN40256812).
We consecutively recruited 7302 patients; 6369 (87.2%) were followed-up. No statistically significant differences were found in re-hospitalisation, neither overall (adjusted percentages: 38.9% in personal continuity, 37.1% in specialisation; odds ratio = 1.08; confidence interval 0.94–1.25; p = 0.28) nor for any of the considered subgroups. There were no significant differences in any of the secondary outcomes.
Whether the same or different psychiatrists provide in- and out-patient treatment appears to have no substantial impact on patient outcomes over a 1-year period. Initiatives to improve long-term outcomes of psychiatric patients may focus on aspects other than the organisation of personal continuity v. specialisation.
Douglas Nakashima, United Nations Educational, Scientific and Cultural Organization (UNESCO), France,Igor Krupnik, Smithsonian Institution, Washington DC,Jennifer T. Rubis, United Nations Educational, Scientific and Cultural Organization (UNESCO), France
Hundreds of thousands of archaeological investigations in the United States conducted over the last several decades have documented a large portion of the recovered archaeological record in the United States. However, if we are to use this enormous corpus to achieve richer understandings of the past, it is essential that both CRM and academic archaeologists change how they manage their digital documents and data over the course of a project and how this information is preserved for future use. We explore the nature and scope of the problem and describe how it can be addressed. In particular, we argue that project workflows must ensure that the documents and data are fully documented and deposited in a publicly accessible, digital repository where they can be discovered, accessed, and reused to enable new insights and build cumulative knowledge.