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Although mania is the hallmark symptom of bipolar I disorder (BD-I), most patients initially present for treatment with depressive symptoms. Misdiagnosis of BD-I as major depressive disorder (MDD) is common, potentially resulting in poor outcomes and inappropriate antidepressant monotherapy treatment. Screening patients with depressive symptoms is a practical strategy to help healthcare providers (HCPs) identify when additional assessment for BD-I is warranted. The new 6-item Rapid Mood Screener (RMS) is a pragmatic patient-reported BD-I screening tool that relies on easily understood terminology to screen for manic symptoms and other BD-I features in <2 minutes. The RMS was validated in an observational study in patients with clinically confirmed BD-I (n=67) or MDD (n=72). When 4 or more items were endorsed (“yes”), the sensitivity of the RMS for identifying patients with BP-I was 0.88 and specificity was 0.80; positive and negative predictive values were 0.80 and 0.88, respectively. To more thoroughly understand screening tool use among HCPs, a 10-minute survey was conducted.
A nationwide sample of HCPs (N=200) was selected using multiple HCP panels; HCPs were asked to describe their opinions/current use of screening tools, assess the RMS, and evaluate the RMS versus the widely recognized Mood Disorder Questionnaire (MDQ). Results were reported by grouped specialties (primary care physicians, general nurse practitioners [NPs]/physician assistants [PAs], psychiatrists, and psychiatric NPs/PAs). Included HCPs were in practice <30 years, spent at least 75% of their time in clinical practice, saw at least 10 patients with depression per month, and diagnosed MDD or BD in at least 1 patient per month. Findings were reported using descriptive statistics; statistical significance was reported at the 95% confidence interval.
Among HCPs, 82% used a tool to screen for MDD, while 32% used a tool for BD. Screening tool attributes considered to be of the greatest value included sensitivity (68%), easy to answer questions (66%), specificity (65%), confidence in results (64%), and practicality (62%). Of HCPs familiar with screening tools, 70% thought the RMS was at least somewhat better than other screening tools. Most HCPs were aware of the MDQ (85%), but only 29% reported current use. Most HCPs (81%) preferred the RMS to the MDQ, and the RMS significantly outperformed the MDQ across valued attributes; 76% reported that they were likely to use the RMS to screen new patients with depressive symptoms. A total of 84% said the RMS would have a positive impact on their practice, with 46% saying they would screen more patients for bipolar disorder.
The RMS was viewed positively by HCPs who participated in a brief survey. A large percentage of respondents preferred the RMS over the MDQ and indicated that they would use it in their practice. Collectively, responses indicated that the RMS is likely to have a positive impact on screening behavior.
To investigate the effect of past depression, past and current eating disorders (ED) on perinatal anxiety and depression in a large general population cohort of pregnant women, the Avon Longitudinal Study of Parents And Children (ALSPAC).
Anxiety and depression were measured during and after pregnancy in 10,887 women, using the Crown-Crisp Experiential Inventory and Edinburgh Postnatal Depression Scale. Women were grouped according to depression and ED history: past ED with (n = 123) and without past depression (n = 50), pregnancy ED symptoms with (n = 77) and without past depression (n = 159), past depression only (n = 818) and controls (n = 9,660). We compared the course of depression and anxiety with linear mixed-effect regression models; and probable depressive and anxiety disorders using logistic regression.
Women with both past depression and past/current ED had high anxiety and depression across time perinatally; this was most marked in the group with pregnancy ED symptoms and past depression (b coefficient:5.1 (95% CI 4.1-6.1), p < 0.0001), especially at 8 months post-partum. At 18 weeks in pregnancy all women (apart from those with past ED only) had a higher risk for a probable depressive and anxiety disorder compared to controls. At 8 months post-partum pregnancy ED symptoms and/or past depression conferred the highest risk for a probable depressive and anxiety disorder.
Pregnancy ED symptoms and past depression have an additive effect in increasing the risk for depression and anxiety perinatally. Screening at risk women for anxiety and depression in the perinatal period might be beneficial.
To evaluate long-term treatment with ziprasidone versus haloperidol (up to 196 weeks), as assessed by PANSS negative score and and its association with quality-of-life (QLS).
The study included two treatment periods: (i) a 40-week, randomized, double-blind phase comparing ziprasidone (ZIP 80-160 mg/d given BID, N=227; ZIP 80-120 mg/d given QD, N=221) versus haloperidol (HAL 5-20 mg/d, N=151), followed by (ii) a 3-year, double-blind extension phase on the same double-blind medications (ZIP BID N=72, ZIP QD N=67, and HAL N=47, respectively). We adapted the Andreasen et al. approach to define negative symptom remission based on attainment of a score ≤3 (mild or less) for at least 6 months on all 7 PANSS negative symptom items. MMRM and GEE models were applied to analyze mean changes in PANSS negative, negative symptom remission rate, and QLS scores over time.
In the 40-week core study, ziprasidone was associated with greater improvement in efficacy and QLS outcomes than haloperidol, but the differences were not statistically significant (p>0.05). However, MMRM analysis of PANSS negative and QLS scores over 196 weeks demonstrated differential treatment effects favoring ziprasidone (80-160 mg/d BID vs. haloperidol) (all p<0.05). Ziprasidone-treated subjects (given BID) were significantly more likely to achieve negative symptom remission (46%) than haloperidol-treated (32%) subjects (p<0.05) during the continuation phase; while ziprasidone given QD (46%) showed a trend to enhanced remission (p<0.08).
These findings support the potential for enhanced social and functional outcomes during long-term treatment with an atypical antipsychotic agent.
The increased prevalence of metabolic syndrome in people with severe mental illness (SMI) is well documented. The International Diabetes Federation (IDF) criteria for metabolic syndrome are three or more of the following: waist circumference ( 80 cm (females), (94 cm (males) OR BMI (30, triglycerides >1.7 mmol/l or on treatment, raised blood pressure (systolic >130 mg Hg or diastolic >85 mm Hg, OR on treatment for hypertension), raised fasting blood glucose (.5.6 mmol/l) OR diagnosed type II diabetes) and reduced HDL cholesterol (< 1.03 mmol/l) OR on treatment.
The IMPACT RCT is a Department of Health funded trial of a health promotion intervention (HPI) delivered by care co-ordinators to people with SMI across South London, Kent and Sussex. The intervention is focussed on improving health by addressing modifiable lifestyle factors such as diet, physical activity, obesity, cigarette smoking, alcohol and substance use.
We investigated the prevalence of metabolic syndrome in a sample of 212 patients for whom we had relevant baseline measures.
Data (weight, BMI, waist circumference, blood pressure, fasting HDL cholesterol, triglycerides and glucose levels) were analysed on 212 patients.
45% of the sample met IDF criteria for metabolic syndrome. Mean BMI was 30.6, glucose 6.4 mmol/L, triglycerides 2.0 mmol/L, HDL 1.2 (mmol/L), waist circumference 105.8 cm, and BP 122/82 mm Hg.
Metabolic syndrome was highly prevalent in this sample, significantly increasing the risk of physical morbidity and potentially lowering life expectancy. There is an unmet need for health promotion interventions in order to lower morbidity and mortality risk in these populations.
Recent information indicates that the number of forensic patients in state hospitals has been increasing, largely driven by an increase in patients referred to state hospitals as incompetent to stand trial (IST). This survey was intended to broaden the understanding of IST population trends on a national level.
The authors developed a 30-question survey to gather specific information on IST commitments in each state and the District of Columbia. The survey was administered to all 50 states and the District of Columbia via email. Specific individuals identified as primary administrators responsible for the care and evaluation of IST admissions in each state were contacted.
A total of 50 out of the 51 jurisdictions contacted completed the survey. Fully 82% of states indicated that referrals for competency evaluation were increasing. Additionally, 78% of respondents thought referrals for competency restoration were increasing. When asked to rank factors that led to an increase, the highest ranked response was inadequate general mental health services in the community. Inadequate crisis services were the second ranked reason. Inadequate number of inpatient psychiatric beds in the community was the third highest, with inadequate assertive community treatment services ranking fourth.
Understanding the national trend and causes behind the recent surge in referrals for IST admissions will benefit states searching for ways to remedy this crisis. Our survey indicates most states are facing this issue, and that it is largely related to insufficient services in the community.
‘DISCOVER’ one-day cognitive behavioural therapy (CBT) workshops have been developed to provide accessible, developmentally sensitive psychological support for older adolescents experiencing emotional difficulties. Previous school-based evaluations of the DISCOVER model have shown positive outcomes.
The current study aimed to test the model for clinically referred adolescents, in real-world settings.
A randomized controlled trial (RCT) assessed feasibility, acceptability and preliminary outcomes of the DISCOVER intervention, in comparison with usual care, for 15- to 18-year-olds with emotional difficulties. Participants were recruited from outpatient clinic waiting lists in UK child and adolescent mental health services (CAMHS). Research feasibility indicators included rates of recruitment, randomization, intervention participation (group workshops and individualized follow-up telephone calls), and data collection (at baseline and 8-week follow-up). Intervention acceptability was assessed using a structured service satisfaction questionnaire and semi-structured qualitative interviews with intervention participants. Preliminary clinical outcomes were explored using adolescent-reported validated measures of depression, anxiety and well-being.
n = 24 participants were randomized to intervention and usual care groups. Workshop attendance was good and high levels of treatment satisfaction were reported, although feasibility challenges emerged in recruitment and randomization. Trends were found towards potential improvements in anxiety and well-being for the intervention group, but the effect estimate for depression was imprecise; interpretability was also limited due to the small sample size.
DISCOVER appears to be a feasible and acceptable intervention model for clinically referred 15- to 18-year-olds with emotional difficulties. A full-scale RCT is warranted to evaluate effectiveness; protocol modifications may be necessary to ensure feasible recruitment and randomization procedures.
Most studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic instruments, and study designs that each has its inherent assumptions, strengths, and biases. We aim to test the homogeneity in heritability estimates between two powerful, and state of the art study designs for eight psychiatric disorders.
We assessed heritability based on data of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on summary data of eight samples with measured genotypes (N = 125 533 cases and 208 215 controls). All data were based on standard diagnostic criteria. Eight psychiatric disorders were studied: (1) alcohol dependence (AD), (2) anorexia nervosa, (3) attention deficit/hyperactivity disorder (ADHD), (4) autism spectrum disorder, (5) bipolar disorder, (6) major depressive disorder, (7) obsessive-compulsive disorder (OCD), and (8) schizophrenia.
Heritability estimates from sibling data varied from 0.30 for Major Depression to 0.80 for ADHD. The estimates based on the measured genotypes were lower, ranging from 0.10 for AD to 0.28 for OCD, but were significant, and correlated positively (0.19) with national sibling-based estimates. When removing OCD from the data the correlation increased to 0.50.
Given the unique character of each study design, the convergent findings for these eight psychiatric conditions suggest that heritability estimates are robust across different methods. The findings also highlight large differences in genetic and environmental influences between psychiatric disorders, providing future directions for etiological psychiatric research.
This Research Communication describes an investigation of the nutritional depletion of total mixed rations (TMR) by pest birds. We hypothesized that species-specific bird depredation of TMR can alter the nutritional composition of the ration and that these changes can negatively impact the performance of dairy cows. Blackbirds selected the high energy fraction of the TMR (i.e., flaked corn) and reduced starch, crude fat and total digestible nutrients during controlled feeding experiments. For Holsteins producing 37·1 kg of milk/d, dairy production modeling illustrated that total required net energy intake (NEI) was 35·8 Mcal/d. For the reference TMR unexposed to blackbirds and the blackbird-consumed TMR, NEI supplied was 41·2 and 37·8 Mcal/d, and the resulting energy balance was 5·4 and 2·0 Mcal/d, respectively. Thus, Holsteins fed the reference and blackbird-consumed TMR were estimated to gain one body condition score in 96 and 254 d, and experience daily weight change due to reserves of 1·1 and 0·4 kg/d, respectively. We discuss these results in context of an integrated pest management program for mitigating the depredation caused by pest birds at commercial dairies.
Recent theories suggest that poor working memory (WM) may be the cognitive underpinning of negative symptoms in people with schizophrenia. In this study, we first explore the effect of cognitive remediation (CR) on two clusters of negative symptoms (i.e. expressive and social amotivation), and then assess the relevance of WM gains as a possible mediator of symptom improvement.
Data were accessed for 309 people with schizophrenia from the NIMH Database of Cognitive Training and Remediation Studies and a separate study. Approximately half the participants received CR and the rest were allocated to a control condition. All participants were assessed before and after therapy and at follow-up. Expressive negative symptoms and social amotivation symptoms scores were calculated from the Positive and Negative Syndrome Scale. WM was assessed with digit span and letter-number span tests.
Participants who received CR had a significant improvement in WM scores (d = 0.27) compared with those in the control condition. Improvements in social amotivation levels approached statistical significance (d = −0.19), but change in expressive negative symptoms did not differ between groups. WM change did not mediate the effect of CR on social amotivation.
The results suggest that a course of CR may benefit behavioural negative symptoms. Despite hypotheses linking memory problems with negative symptoms, the current findings do not support the role of this cognitive domain as a significant mediator. The results indicate that WM improves independently from negative symptoms reduction.
A significant minority of people presenting with a major depressive episode (MDE) experience co-occurring subsyndromal hypo/manic symptoms. As this presentation may have important prognostic and treatment implications, the DSM–5 codified a new nosological entity, the “mixed features specifier,” referring to individuals meeting threshold criteria for an MDE and subthreshold symptoms of (hypo)mania or to individuals with syndromal mania and subthreshold depressive symptoms. The mixed features specifier adds to a growing list of monikers that have been put forward to describe phenotypes characterized by the admixture of depressive and hypomanic symptoms (e.g., mixed depression, depression with mixed features, or depressive mixed states [DMX]). Current treatment guidelines, regulatory approvals, as well the current evidentiary base provide insufficient decision support to practitioners who provide care to individuals presenting with an MDE with mixed features. In addition, all existing psychotropic agents evaluated in mixed patients have largely been confined to patient populations meeting the DSM–IV definition of “mixed states” wherein the co-occurrence of threshold-level mania and threshold-level MDE was required. Toward the aim of assisting clinicians providing care to adults with MDE and mixed features, we have assembled a panel of experts on mood disorders to develop these guidelines on the recognition and treatment of mixed depression, based on the few studies that have focused specifically on DMX as well as decades of cumulated clinical experience.
Runaway electrons, which are generated in a plasma where the induced electric field exceeds a certain critical value, can reach very high energies in the MeV range. For such energetic electrons, radiative losses will contribute significantly to the momentum space dynamics. Under certain conditions, due to radiative momentum losses, a non-monotonic feature – a ‘bump’ – can form in the runaway electron tail, creating a potential for bump-on-tail-type instabilities to arise. Here, we study the conditions for the existence of the bump. We derive an analytical threshold condition for bump appearance and give an approximate expression for the minimum energy at which the bump can appear. Numerical calculations are performed to support the analytical derivations.
The aims of the study were to determine the prevalence of cardiometabolic risk factors and establish the proportion of people with psychosis meeting criteria for the metabolic syndrome (MetS). The study also aimed to identify the key lifestyle behaviours associated with increased risk of the MetS and to investigate whether the MetS is associated with illness severity and degree of functional impairment.
Baseline data were collected as part of a large randomized controlled trial (IMPaCT RCT). The study took place within community mental health teams in five Mental Health NHS Trusts in urban and rural locations across England. A total of 450 randomly selected out-patients, aged 18–65 years, with an established psychotic illness were recruited. We ascertained the prevalence rates of cardiometabolic risk factors, illness severity and functional impairment and calculated rates of the MetS, using International Diabetes Federation (IDF) and National Cholesterol Education Program Third Adult Treatment Panel criteria.
High rates of cardiometabolic risk factors were found. Nearly all women and most men had waist circumference exceeding the IDF threshold for central obesity. Half the sample was obese (body mass index ≥ 30 kg/m2) and a fifth met the criteria for type 2 diabetes mellitus. Females were more likely to be obese than males (61% v. 42%, p < 0.001). Of the 308 patients with complete laboratory measures, 57% (n = 175) met the IDF criteria for the MetS.
In the UK, the prevalence of cardiometabolic risk factors in individuals with psychotic illnesses is much higher than that observed in national general population studies as well as in most international studies of patients with psychosis.
The aim of the present study was to examine the association of pre-pubertal dietary energy density (ED) with both age and body fatness at the start of the pubertal growth spurt (age at take-off, ATO). Analyses included 219 DOrtmund Nutritional and Anthropometric Longitudinally Designed Study participants with sufficient height measurements to estimate ATO who provided 3 d weighed dietary records at baseline, i.e. 2 and 3 years before ATO (mean age 6·9 (sd 1·2) years). Mean energy intakes and amounts of foods/drinks consumed at baseline were derived from the records. ED (kJ/g) was calculated based on (1) all foods and drinks (ED_all), (2) foods and energy-containing drinks (ED_energy), (3) foods and milk as a drink, but no other beverages (ED_milk) and (4) foods only, solid or liquid (ED_food). Using multiple regression analyses, the association between the ED variables and ATO was investigated. Furthermore, Z-scores of BMI and fat mass index (FMI) at ATO were considered as outcomes to reflect body fatness at puberty onset. The results showed that ED at baseline was not associated with ATO, regardless of the ED method used. For example, mean ATO in the lowest v. highest tertile of ED_food was 9·3 (95 % CI 9·0, 9·5) v. 9·4 (95 % CI 9·1, 9·7) years, Ptrend = 0·8 (adjusted for sex, maternal age, birth weight, dietary protein, dietary fibre, baseline BMI Z-score). Similarly, ED was not independently associated with BMI or FMI Z-score at ATO (Ptrend = 0·3–0·9). In conclusion, dietary ED in childhood did not influence timing or body fatness at ATO in this cohort of healthy, free-living children.
Cognitive behaviour therapies (CBTs) have through several trials been demonstrated to reduce symptoms and disability in irritable bowel syndrome (IBS) patients, but the mechanisms responsible for the changes are still unknown. The aim of this study was to test a theoretical model of CBT and investigate if cognitions and/or behaviour mediated the changes seen in CBT for IBS.
To assess for possible mediating effects, we applied path analysis to the dataset of 149 diagnosed participants randomized to mebeverine hydrochloride plus CBT or mebeverine hydrochloride alone. Primary outcome was symptom severity, while secondary outcomes were work and social adjustment and anxiety.
The path analyses supported mediational paths for all outcomes. Changes in behaviour and cognitions mediated all three outcomes, with models placing behaviour change ‘upstream’ of cognition change having best fit. The analyses of model fits revealed best fit for the anxiety model and hence provide increased confidence in the causal model of anxiety.
Changes in behaviour and cognitions mediate the change in CBT given to IBS patients. The results strengthen the validity of a theoretical model of CBT by confirming the interaction of cognitive, emotional and behavioural factors in IBS.
Medical education often presents new material as large data dumps at a single live event (lecture or symposium), in part because it is traditional, and also because this structure can be perceived as the most time efficient for busy clinicians and their teachers. However, modern learning theory and new insights from the neurobiological basis of long-term memory formation show that the format of single-event presentation of materials is not very effective. Rather, seeing the presentation of new materials over time, in bite-sized chunks, and then seeing them again at a later time, particularly as a test, leads to more retention of information than does learning the same amount of material as a large bolus in a single setting. This notion of learning over time, also called “interval learning” or “spaced learning,” is particularly well adapted to the Internet era. Here we describe an application of this concept to the learning of psychopharmacology over time in bite-sized and repeated portions structured as an “online fellowship” called the Master Psychopharmacology Program (www.neiglobal.com/mpptour).
Visual and verbal episodic memory deficits are putative endophenotypes for schizophrenia; however, the extent of any genetic overlap of these with schizophrenia is unclear. In this study, we set out to quantify the genetic and environmental contributions to variance in visual and verbal memory performance, and to quantify their genetic relationship with schizophrenia.
We applied bivariate genetic modelling to 280 twins in a classic twin study design, including monozygotic (MZ) and dizygotic (DZ) pairs concordant and discordant for schizophrenia, and healthy control twins. We assessed episodic memory using subtests of the Wechsler Memory Scale – Revised (WMS-R).
Genetic influences (i.e. heritability) contributed significantly to variance in immediate recall of both verbal memory and visual learning, and the delayed recall of verbal and visual memory. Liability to schizophrenia was associated with memory impairment, with evidence of significant phenotypic correlations between all episodic memory measures and schizophrenia. Genetic factors were the main source of the phenotypic correlations for immediate recall of visual learning material; both immediate and delayed recall of verbal memory; and delayed recall of visual memory that, for example, shared genetic variance with schizophrenia, which accounted for 88% of the phenotypic correlation (rph=0.41) between the two.
Verbal memory and visual learning and memory are moderately heritable, share a genetic overlap with schizophrenia and are valid endophenotypes for the condition. The inclusion of these endophenotypes in genetic association studies may improve the power to detect susceptibility genes for schizophrenia.