CRISPR/Cas9-generated mutations in a sugar transporter gene reduce cassava susceptibility to bacterial blight.

Bacteria from the genus Xanthomonas are prolific phytopathogens that elicit disease in over 400 plant species. Xanthomonads carry a repertoire of specialized proteins called transcription activator-like (TAL) effectors that promote disease and pathogen virulence by inducing expression of host susceptibility (S) genes. Xanthomonas phaseoli pv. manihotis (Xpm) causes bacterial blight on the staple food crop cassava (Manihot esculenta Crantz). The Xpm effector TAL20 induces ectopic expression of the S gene Manihot esculenta Sugars Will Eventually be Exported Transporter 10a (MeSWEET10a), which encodes a sugar transporter that contributes to cassava bacterial blight susceptibility. We used CRISPR/Cas9 to generate multiple cassava lines with edits to the MeSWEET10a TAL20 effector binding site and/or coding sequence. In several of the regenerated lines, MeSWEET10a expression was no longer induced by Xpm, and in these cases, we observed reduced cassava bacterial blight (CBB) disease symptoms post Xpm infection. Because MeSWEET10a is expressed in cassava flowers, we further characterized the reproductive capability of the MeSWEET10a promoter and coding sequence mutants. Lines were crossed to themselves and to wild-type plants. The results indicated that expression of MeSWEET10a in female, but not male, flowers, is critical to produce viable F1 seed. In the case of promoter mutations that left the coding sequence intact, viable F1 progeny were recovered. Taken together, these results demonstrate that blocking MeSWEET10a induction is a viable strategy for decreasing cassava susceptibility to CBB and that ideal lines will contain promoter mutations that block TAL effector binding while leaving endogenous expression of MeSWEET10a unaltered.

Lifestyle and incident dementia: A COSMIC individual participant data meta­analysis.

INTRODUCTION: The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics. METHODS: We combined data from 21 prospective cohorts across six continents (N = 31,680) and conducted cohort-specific Cox proportional hazard regression analyses in a two-step individual participant data meta-analysis. RESULTS: A one-standard-deviation increase in LIBRA score was associated with a 21% higher risk for dementia. The association was stronger for Asian cohorts compared to European cohorts, and for individuals aged ≤75 years (vs older), though only within the first 5 years of follow-up. No interactions with sex, education, or socioeconomic position were observed. DISCUSSION: Modifiable risk and protective factors appear relevant for dementia risk reduction across diverse geographical and sociodemographic groups. HIGHLIGHTS: A two-step individual participant data meta-analysis was conducted. This was done at a global scale using data from 21 ethno-regionally diverse cohorts. The association between a modifiable dementia risk score and dementia was examined. The association was modified by geographical region and age at baseline. Yet, modifiable dementia risk and protective factors appear relevant in all investigated groups and regions.

Mapping Cognitive Trajectories and Detecting Early Dementia Using the Mini-Mental State Examination Cognitive Charts: Application to the French Three-City Cohort.

The Cognitive Quotient (QuoCo) classification algorithm monitoring decline on age- and education-adjusted Mini-Mental State Examination (MMSE)-derived cognitive charts has proved superior to the conventionally-used cut-off for identifying incident dementia; however, it remains to be tested in different settings. Data were drawn from the Three-City Cohort to 1) assess the screening accuracy of the QuoCo, and 2) compare its performance to that of serial MMSE tests applying different cut-offs. For the QuoCo, sensitivity was 74.2 (95% CI: 71.4-76.8) and specificity 84.1 (83.6-84.7) and for the MMSE < 24, 64.1 (61.1-67.0) and 94.8 (94.4-95.1), respectively; whereas overall accuracy and sensitivity was highest for MMSE cut-offs <25 and <26. User-friendly charts for mapping cognitive trajectories over visits with an alert for potentially 'abnormal' decline can be of practical use and encourage regular monitoring in primary care where the <24 cut-off is still widely used despite its poor sensitivity.

Trauma and mental health in young adults who arrived in France as unaccompanied and separated migrant children.

OBJECTIVES: The mental health of unaccompanied and separated minors (UASC) has been widely studied but not their first years of adulthood, often characterised by uncertainty after leaving child protection. The aim of this study was to estimate the prevalence of psychiatric disorders using standardised and validated research instruments and examine the effect of exposure to trauma. METHODS: One hundred and ten youth (92.7% male, median age 19.7 [18.1-22.8]) from Chambery, Montpellier and La Rochelle were recruited to a cross-sectional exploratory study. During a face-to-face interview, somatoform disorder, anxiety, and depression were assessed using the Patient Health Questionnaire (score≥10) and post-traumatic stress disorder (PTSD) with the PTSD Checklist for DSM-5 (score≥33). Traumatic life events were assessed using the Life Events Checklist. RESULTS: Of the youth, 19.3% had a probable somatoform disorder, 17.6% anxiety, 28.7% depression, and 20% PTSD. The number of traumatic life events increased the risk of depression (multi-adjusted OR (95%CI): 1.56 (1.25-1.96)), PTSD (1.60 (1.23-2.08)), somatoform disorder (1.41 (1.10-1.82), and anxiety (1.33 (1.02-1.72)). Physical assault was the type of event positively associated with the most disorders (P≤0.01, except for anxiety), followed by witnessing sudden and violent death (P≤0.01 for depression and PTSD) and sexual assault (P=0.002 for PTSD). CONCLUSION: Our study highlights the high prevalence of psychiatric disorders in young adults who arrived as UASC and the impact on their mental health of cumulative trauma and exposure to interpersonal and violent traumatic life events. A greater focus on their mental health with regular assessments is needed in order to provide rapid and adapted care.

Association between uncertainty regarding right-to-stay and mental health in unaccompanied and separated migrant children (UASC) reaching adulthood: findings from France.

PURPOSE: There is substantial evidence suggesting high levels of mental health problems in unaccompanied and separated children (UASC). However, there is less focus on the first years of adulthood characterised by increased vulnerability and fear of expulsion. We aimed to describe the mental health of UASC on reaching adulthood, and how this was affected by uncertainty regarding their right-to-stay in France. METHODS: One hundred and ten youth aged 18-22 were recruited via child protection reception centres. We administered the Patient Health Questionnaire somatic (PHQ-15), anxiety (GAD-7) and depression (PHQ-9) modules, the Post-Traumatic Stress Disorder Checklist (PCL-5) and Connor-Davidson Resilience Scale (CD-RISC-10). Logistic regression analysis was performed with the dependent variable, a secure (versus uncertain) situation, defined as (1) detaining a residence permit and being in school, an apprenticeship or a salaried job, or (2) waiting for residence permit whilst occupying a salaried job. RESULTS: Of the sample, 19.3% reached criteria for a probable somatic disorder, 17.6% for anxiety and 28.7% for depression (score  ≥ 10); 41.8% were in an uncertain situation regarding their right-to-stay. Uncertainty was associated with higher anxiety ((OR per Interquartile range (95% CI), 1.77 (1.05-2.98)) and post-traumatic stress symptoms (2.05 (1.06-4.00)), lower resilience (0.50 (0.27-0.91)), and participants rating their anxiety (p = 0.02) and depressive symptoms (p = 0.003) as more severe since reaching adulthood. CONCLUSIONS: Our findings suggest uncertainty regarding right-to-stay is associated with increased mental health symptoms, specifically anxiety and trauma-induced stress, thereby highlighting the vulnerability of UASC in their first years of adulthood. This calls for greater support during this transition period with regular symptom monitoring for timely psychological interventions.

Improving cassava bacterial blight resistance by editing the epigenome.

Pathogens rely on expression of host susceptibility (S) genes to promote infection and disease. As DNA methylation is an epigenetic modification that affects gene expression, blocking access to S genes through targeted methylation could increase disease resistance. Xanthomonas phaseoli pv. manihotis, the causal agent of cassava bacterial blight (CBB), uses transcription activator-like20 (TAL20) to induce expression of the S gene MeSWEET10a. In this work, we direct methylation to the TAL20 effector binding element within the MeSWEET10a promoter using a synthetic zinc-finger DNA binding domain fused to a component of the RNA-directed DNA methylation pathway. We demonstrate that this methylation prevents TAL20 binding, blocks transcriptional activation of MeSWEET10a in vivo and that these plants display decreased CBB symptoms while maintaining normal growth and development. This work therefore presents an epigenome editing approach useful for crop improvement.

Validation of KASP-SNP markers in cassava germplasm for marker-assisted selection of increased carotenoid content and dry matter content.

Provitamin A biofortification and increased dry matter content are important breeding targets in cassava improvement programs worldwide. Biofortified varieties contribute to the alleviation of provitamin A deficiency, a leading cause of preventable blindness common among pre-school children and pregnant women in developing countries particularly Africa. Dry matter content is a major component of dry yield and thus underlies overall variety performance and acceptability by growers, processors, and consumers. Single nucleotide polymorphism (SNP) markers linked to these traits have recently been discovered through several genome-wide association studies but have not been deployed for routine marker-assisted selection (MAS). This is due to the lack of useful information on markers' performances in diverse genetic backgrounds. To overcome this bottleneck, technical and biological validation of the loci associated with increased carotenoid content and dry matter content were carried out using populations independent of the marker discovery population. In the present study, seven previously identified markers for these traits were converted to a robust set of uniplex allele-specific polymerase chain reaction (PCR) assays and validated in two independent pre-breeding and breeding populations. These assays were efficient in discriminating marker genotypic classes and had an average call rate greater than 98%. A high correlation was observed between the predicted and observed carotenoid content as inferred by root yellowness intensity in the breeding (r = 0.92) and pre-breeding (r = 0.95) populations. On the other hand, dry matter content-markers had moderately low predictive accuracy in both populations (r< 0.40) due to the more quantitative nature of the trait. This work confirmed the markers' effectiveness in multiple backgrounds, therefore, further strengthening their value in cassava biofortification to ensure nutritional security as well as dry matter content productivity. Our study provides a framework to guide future marker validation, thus leading to the more routine use of markers in MAS in cassava improvement programs.

Psychometric properties of the BIRT Motivation Questionnaire (BMQ), a self-measure of avolition in individuals with schizophrenia.

AIMS: Avolition defined as a lack of interest or engagement in goal-directed behavior plays a key role in everyday functioning in schizophrenia and is considered as one of the main contributors to the burden of disease. The aim of this study was to 1) validate the self-report BIRT Motivation Questionnaire (BMQ-S) seldom used before in schizophrenia 2) examine the degree of agreement between the BMQ-S and its informant-report version 3) to assess its ability to predict real-world outcome at 12 month follow-up. METHODS: One hundred and twenty-two (51.9% inpatients) adults with a diagnosis of schizophrenia were included. Exploratory Factor analysis was performed on the BMQ-S to identify the underlying structure. Real life functioning was measured with the Global Assessment of Functioning scale (GAF). Convergent validity was assessed with the Scale for Assessment of Negative Symptom (SANS) and the Lille Apathy Rating Scale (LARS). RESULTS: The main psychometric properties of the BMQ-S (internal consistency, test-retest reliability) were satisfactory. Exploratory factorial analysis revealed a 4-factor model which explained 76% of the overall variance. The BMQ-S correlated significantly with the LARS and the SANS avolition subscore suggesting adequate convergent validity. The correlation between the BMQ-S and the clinician-report version was 0.48. The global score and in particular the Initiation/disorganisation dimension was a significant predictor of global functioning at 12-months even when adjusted for age, chlorpromazine intake and depression. CONCLUSION: Our findings indicate that the BMQ-S has satisfactory psychometric properties and that schizophrenia patients can reliably assess their lack of motivation. Self-evaluation of avolition should be considered in the overall prediction of real-world functioning in schizophrenia.

Importance of Patient Education for At-home Yoga Practice in Women With Hormonal Therapy-induced Pain During Adjuvant Breast Cancer Treatment: A Feasibility Study.

BACKGROUND: Osteo-articular pain (OAP) is experienced by approximately 50% of women under hormonal therapy (HT) for breast cancer (BC), which increases the risk for therapy discontinuation. This study was aimed to assess benefits of yoga practice combined with patient education (PE) for at-home practice by evaluating feasibility among BC patients under HT and measuring OAP, flexibility and satisfaction. METHODS: Feasibility was evaluated by patient adherence as accomplishment of at least 4 out of 6 supervised yoga-PE sessions along with 70% or more at-home yoga sessions. Intervention (12 weeks) included two 6-weeks periods: P1 comprising one 90-minutes supervised yoga-PE session/week and 15-minutes daily at-home yoga and P2, daily autonomous at-home yoga sessions. Evaluations (at inclusion and by the end of each period) consisted in assessment of OAP on Visual Analog Scale (VAS), forward flexibility (cm) and patient satisfaction on Likert (0-10 points) scale. RESULTS: Between September 2018 and May 2019 we included 24 patients of median 53 years (range 36-72). Feasibility was validated by 83% successful adherence rate. Pain was significantly reduced from median VAS of 6 [range 4-10] to 4 [range 0-7] at the end of both P1 and P2 (p < 0.01), albeit with no difference between P1 and P2. Forward flexibility improved by a median gain of 8 cm (end of P2) and median satisfaction score of 10/10 [range 8-10]. CONCLUSION: Combined physiotherapy-yoga-PE intervention is a feasible strategy to increase at-home yoga practice with potential benefit on pain, flexibility, and satisfaction, thus prompting further evaluations in larger randomized multicenter trials. CLINICALTRIALS.GOV: NCT04001751.

A Prospective Study of Diurnal Cortisol and Incident Dementia in Community-Dwelling Older Adults.

Diurnal salivary cortisol was measured in 334 older adults without dementia, at four times on two separate days, under quiet and stressful conditions. In multivariate Cox proportional hazard models, higher global diurnal cortisol secretion was associated with incident dementia (HR = 1.09 [1.02-1.15] per one-unit increase in cortisol measure, p = 0.007) and Alzheimer's disease (HR = 1.12 [1.04-1.21], p = 0.003) over a mean (SD) of 8.1 (4.0) years, independent of potential confounders and stressful conditions. Individuals with incident dementia had a slower rate of cortisol elimination under non-stressful conditions, reflected by higher cortisol levels in the evening, and an abnormal response to stress (blunted evening stress response).

Comparison of three scales (BIS, SUMD and BCIS) for measuring insight dimensions and their evolution after one-year of follow-up: Findings from the FACE-SZ Cohort.

The aim of our study was to compare the performance of three different instruments measuring clinical and cognitive dimensions of insight. Data on 182 outpatients with schizophrenia and one-year follow-up assessments was drawn from the FACE-SZ cohort. Awareness of clinical state (« clinical insight ¼) was measured using both a clinician-rated measure (the Scale to assess Unawareness of Mental Disorder (SUMD)), and a self-report measure (the Birchwood Insight Scale (BIS). Cognitive insight was measured using a self-report measure (the Beck Cognitive Insight Scale (BCIS)). For each scale, change in insight was examined at the follow-up. Correlations between SUMD and BIS subscales measuring same dimensions were significant. BIS-BCIS correlations were weak for all combinations except between BIS illness dimension and BCIS composite score. At the follow-up, BIS and SUMD awareness of treatment need improved whereas illness and symptom awareness increased only on the SUMD. Conversely, cognitive insight composite scores decreased. Despite relatively good overall agreement between the two clinical insight instruments, considerable variability for similar insight dimensions measured by different instruments was found. Agreement between cognitive and clinical insight is moderate. Our study strengthens the argument that insight is harder to operationalize than other symptoms and may explain why it is so seldom explicitly targeted in schizophrenia treatment.

Steroid 21-hydroxylase gene variants and late-life depression.

OBJECTIVES: A feature of late-life depression is alterations of the stress hormone system. The CYP21A2 gene encodes for the steroid 21-hydroxylase enzyme which is required for the biosynthesis of mineralocorticoids and glucocorticoids, two main components of the stress response in humans. Variants in the CYP21A2 gene could influence risk of late-life depression, but this has not been examined. This study investigated possible associations between five variants in the CYP21A2 gene and late-life depression in 1007 older community-dwelling men and women. RESULTS: In multivariate logistic regression model, significant associations were found between three single-nucleotide polymorphisms (rs389883, rs437179, and rs630379) and depression in women specifically (OR ranging from 1.51 to 1.68, p-values 0.025 to 0.0045), and the two latter remained significant after correction for multiple testing. Variants of the CYP21A2 gene appear as susceptibility factors for late-life depression in a sex-specific manner, independently of somatic and neuropsychiatric comorbidity.

The association between anxiety disorders and hippocampal volume in older adults.

The hippocampus, through its mediation of fear responses is thought to play a central role in the onset and maintenance of anxiety disorders. Prevalence of anxiety disorders remains high in older populations; however, little is known about their association with hippocampal changes in this age group. Due to differing levels of cortisol as adults age, age-related decreases in hippocampal volume, and the suggestion that age-related loss of neurogenesis results in anxiety disorders, this area requires investigation. We examined the association between hippocampal volume and anxiety disorders (social anxiety disorder, generalized anxiety disorder, agoraphobia, panic disorder, obsessive compulsive disorder and posttraumatic stress disorder) in 534 older adults participating in the Enquête de Santé Psychologique-Risques, Incidence et Traitement (ESPRIT) study of late-life neuropsychiatric disorders. Anxiety disorders were diagnosed using the Mini International Neuropsychiatric Interview MINI, French version 5.00. Cross-sectional analyses adjusted for age, educational level, gender, Mini-Mental State Examination scores, National Adult Reading Test scores, whole brain volume and depression found that a diagnosis of generalized anxiety disorder was positively associated with larger hippocampal volume. No other anxiety disorder was significantly associated with hippocampal volume. The present study is the first to examine the association between several anxiety disorders and hippocampal volume in an older population and the results highlight the need for further research relating to the relationship between hippocampal volume and anxiety disorders in older adults. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Time-dependent depression and anxiety symptoms as risk factors for recurrent cardiac events: findings from the UPBEAT-UK study.

BACKGROUND: Depression is a well-known risk factor for recurrent cardiac events (RCEs) but findings are less consistent for anxiety, not previously reported on using a time-dependent approach. We aimed to study the prognostic effect of anxiety and depression symptom levels on RCEs. METHODS: Data (N = 595) were drawn from the UPBEAT-UK heart disease patient cohort with 6-monthly follow-ups over 3 years. Hospital Anxiety and Depression Scale symptoms were grouped into: agitation (three items), anxiety (four items), and depression (seven items) subscales. We performed two types of multivariate analyses using Cox proportional hazard models with delayed entry: with baseline variables (long-term analysis), and with variables measured 12-to-18 months prior to the event (short-term time-dependent analysis), as RCE risk factors. RESULTS: In the baseline analysis, both anxiety and depression, but not agitation, were separate RCE risk factors, with a moderating effect when considered jointly. In the short-term time-dependent analysis, elevated scores on the anxiety subscale were associated with increased RCE risk even when adjusted for depression [hazard ratio (95% confidence interval) 1.22 (1.05-1.41), p = 0.009]. Depression was no longer a significant predictor when adjusted for anxiety [1.05 (0.87-1.27), p = 0.61]. For anxiety, individual items associated with RCEs differed between the two approaches: item 5 'worrying thoughts' was the most significant long-term risk factor [1.52 (1.21-1.91), p = 0.0004] whereas item 13 'feelings of panic' was the most significant time-dependent short-term risk factor [1.52 (1.18-1.95), p = 0.001]. CONCLUSIONS: Anxiety is an important short-term preventable and potentially causal risk factor for RCEs, to be targeted in secondary cardiac disease prevention programmes.

11ß-Hydroxylase (CYP11B1) gene variants and new-onset depression in later life.

Background: Cumulative exposure to high glucocorticoid levels is detrimental for the brain and may have particular implications in later life. A feature of late-life depression is increased cortisol secretion. Variants in the CYP11B1 gene, which codes for the enzyme responsible for cortisol synthesis, could influence risk of late-life depression, but this hypothesis has not been examined. We investigated the associations between variants in the CYP11B1 gene and late-life depression, taking into account history of depression and potential sex-specific effects. Methods: We assessed depression in 1007 community-dwellers aged 65 years or older (60% women) at baseline and over a 14-year follow-up. A clinical level of depression was defined as a score of ≥ 16 on the Centre for Epidemiology Studies Depression scale or a diagnosis of current major depression based on the Mini-International Neuropsychiatric Interview and according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV). We examined incident and recurrent depression in participants without or with a history of major depression, respectively. We genotyped 5 single-nucleotide polymorphisms (SNPs) spanning CYP11B1. We used multivariable analyses to adjust for age, body mass index, cardiovascular ischemic pathologies, hypertension, cognitive impairment and anxiety. Results: In women, rs6471580 and rs7016924 were associated with a 50% lower rate of incident (new-onset) late-life depression, and rs11783855 was associated with a 2.4-fold higher rate of late-life depression. These associations remained after correction for multiple testing, but we found no associations for recurrent depression in women or men. Limitations: This study focused on the major gene involved in corticosteroid biosynthesis, but other genes may also be implicated in this pathway. Conclusion: Variants of the CYP11B1 gene appear to be susceptibility factors for late-life depression in a sex-specific manner.

Assessment of the efficacy of a fatigue management therapy in schizophrenia: study protocol for a randomized, controlled multi-centered study (ENERGY).

BACKGROUND: Fatigue is a well-known common clinical feature of numerous chronic diseases including various forms of cancer, neurological disorders such as multiple sclerosis, and psychiatric disorders. A significant proportion of people with schizophrenia (30-60%) reportedly experience fatigue, which impacts negatively on participation in various activities, including work, study, leisure, and social pursuits. Causes of fatigue in schizophrenia are poorly understood and there are no established treatments. Several evidence-based interventions for fatigue syndrome including psychoeducation, cognitive behavioral therapy, and graded exercise therapy have been shown to be effective in other medical conditions and could be adapted to address fatigue in schizophrenia patients. As there are no psychosocial or pharmacological interventions with proved efficacy for fatigue in schizophrenia, there is an urgent need for the development of strategies to improve fatigue management in schizophrenia. The aim of this project is to evaluate in a single blind randomized clinical trial the efficacy of a cognitive-behavioral therapy (CBT) intervention compared to treatment as usual (TAU) on fatigue as the main outcome in schizophrenia patients. Clinical symptoms, physical functioning, major cognitive functions, quality of life and functioning, treatment dosage, daily motor activity, biological markers with inflammatory markers are also considered as secondary outcomes. METHODS/DESIGN: Two hundred patients meeting the inclusion criteria will be randomized to either of the study arms (intervention or TAU). The ENERGY intervention will be delivered according to a standardized treatment manual comprising six modules addressing fatigue and sleep over 14 individual therapy sessions. The treatment encompasses core CBT principles of psycho-education, behavioral activation, behavioral experiments, cognitive restructuring, problem-solving, and relapse prevention. Sessions will follow the traditional CBT structure of agenda setting, review of homework tasks, and introduction of a new concept/technique with collaborative discussions on how to implement such strategies in the participant's day-to-day environment. Our primary endpoint will be the severity of fatigue assessed at baseline and at the 9-month follow-up using the "Multidimensional Fatigue Inventory" (MFI). DISCUSSION: The trial will provide the first test of CBT intervention for fatigue for patients with schizophrenia. This study will also test to what extent the treatment can be implemented in everyday practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT04332601 . Registered on 10 April 2020.

Using a citizens' jury approach to determine a good nutrition resource for pregnant women.

OBJECTIVE: The development of user-friendly nutrition resources for pregnant women seldom involves end-users. This qualitative study used a citizens' jury approach to determine if our modification of a longstanding, frequently used dietitian-informed diet and diabetes booklet was deemed to be a good healthy eating resource for pregnant women. DESIGN: Midwives recruited thirteen first-time pregnant women not requiring specialist obstetric care or specialist dietetic advice for any reason. Participants were sent a copy of the modified healthy eating in pregnancy booklet prior to 'jury day'. Five women were unable to attend the citizens' jury citing reasons such as early labour. At the jury, five experts presented evidence. Participants adjourned, with an independent facilitator, to 'deliberate' as to whether the resource was suitable or not. The verdict was presented, and subsequent discussion was audio-recorded, transcribed and inductively content analysed. SETTING: Southland, New Zealand. PARTICIPANTS: Pregnant women aged 19-35 years (n 8), of whom half had a household income <$NZ30 000. RESULTS: The verdict was 'Yes'; the resource was good. Three themes were derived: communication of health information, resource content and harm reduction in pregnancy. Based on these data, ways to enhance the quality and usability of the booklet were evident. CONCLUSIONS: Citizens' juries can be used to obtain an independent assessment by end-users of health resources. Our modified diet and diabetes booklet was considered suitable for providing healthy eating advice to pregnant women. Inclusion of end-users' perspectives is critical for end-user relevant content, comprehension and resource credibility.

Aromatase (CYP19A1) gene variants, sex steroid levels, and late-life depression.

BACKGROUND: Sex differences in psychiatric disorders are common and could involve sex steroids. Aromatase, the product of the CYP19A1 gene, is the key enzyme in the conversion of androgen to estrogen. Whether CYP19A1 variants could be associated with depression differently in men and women has not been examined. METHODS: This population-based study included 405 men and 602 women aged ≥65 years. A clinical level of depression (DEP) was defined as having a score ≥16 on the Center for Epidemiology Studies Depression scale or a diagnosis of current major depression based on the Mini-International Neuropsychiatric Interview and according to DSM-IV criteria. Seven single-nucleotide polymorphisms (SNPs) spanning the CYP19A1 gene were genotyped and circulating levels of estradiol and testosterone were determined. Multivariable analyses were adjusted for age, body mass index, ischemic pathologies, cognitive impairment, and anxiety. RESULTS: Five SNPs were associated with DEP in women specifically and this varied according to a history of major depression (p-values .01 to .0005). Three SNPs were associated with an increased risk of late-life DEP in women without a history of major depression, while two SNPs were associated with a decreased DEP risk in women with a history of major depression and were also associated with higher estradiol levels. CONCLUSIONS: Variants of the CYP19A1 gene appear to be susceptibility factors for late-life depression in a sex-specific manner. The polymorphisms decreasing the risk of recurrent depression in postmenopausal women also influence estradiol levels.

Sex-specific depressive symptoms as markers of pre-Alzheimer dementia: findings from the Three-City cohort study.

Late-life depression, as a potential marker of pre-dementia, has seldom been explored by symptom dimension and sex, despite sexual dimorphic differences. This study aimed to examine whether specific depressive dimensions were associated with pre-Alzheimer's disease dementia (pre-AD), separately for women and men. Data were drawn from 5617 (58% women) community-dwellers aged 65+ recruited in 1999-2000 and followed at 2-year intervals for 12 years. We used Cox proportional hazard models to study associations between time-dependent Centre for Epidemiologic Studies-Depression Scale (CES-D) symptom dimensions (namely somatic, depressed, positive affect, and interpersonal challenge) and pre-AD, defined retrospectively from validated diagnoses established 3.5 (IQR: 3.2-4.0) years onwards. Analyses were performed according to overall depressive symptomatology (DS+: CES-D score ≥ 16) and antidepressant/anxiolytic medication use (AA). Results indicated that in DS+ women only, all four dimensions were significantly associated with pre-AD in the AA- group, in particular somatic item 'Mind' and depressed affect items 'Depressed' and 'Blues'. The most depression-specific dimension, depressed affect, was also significantly associated with pre-AD in the DS- AA- women (HR:1.28, 95%CI: 1.12;1.47). In both sexes, in the DS- groups somatic affect was the most robust pre-AD marker, irrespective of treatment (women: HR = 1.22, 95%CI: 1.08;1.38; men: HR = 1.30, 95%CI: 1.14;1.48). Our findings highlight sex-specific associations between depressive symptom dimensions and pre-AD, modulated by depressive symptomatology and treatment. Assessment of specific symptom dimensions taking into account overall symptomatology and treatment could help identify and target high-risk AD-dementia profiles for interventions.

The contribution of optimism and hallucinations to grandiose delusions in individuals with schizophrenia.

Grandiose delusions (GDs) are defined as false beliefs about having an inflated worth, power, or a special identity which are firmly sustained despite undeniable evidence to the contrary. Although it is the second most commonly encountered delusional beliefs, GDs have received little attention. Thus, in this study, we explored the role of future expectations and sensitivity to reward in GDs in schizophrenia (SZ) disorder. In total, 115 SZ patients completed measures of positive and negative symptoms, sensitivity to reward, depression, and a task in which individuals were asked to estimate the probability that positive, negative and neutral events will occur in the future. Correlation and Linear Regression analyses were performed in order to determine whether sensitivity to reward and future expectations are associated with GDs. Regressions showed that hallucinations and future positive expectations were significantly associated with GDs. In conclusion, the present study showed that higher optimism regarding the future might be important psychological processes associated with the maintenance of GDs in SZ patients. Moreover, it is possible that patients experiencing hallucinations may interpret this phenomenon as a kind of special ability or power, resulting in turn in GDs maintenance. Implications of these findings and directions for future research are discussed.