Perfect Enough to Sleep? Perfectionism and Actigraphy-Determined Markers of Insomnia.

OBJECTIVES: Perfectionism is an important factor in insomnia development and maintenance. Previous studies exploring the relationship between perfectionism and insomnia have predominantly relied on self-reported sleep measures. Therefore, this study sought to assess whether actigraphy-measured sleep parameters were associated with perfectionism. METHODS: Sixty adults (85% females, mean age 30.18 ± 11.01 years) were sampled from the Australian general population. Actigraphy-derived objective sleep measures, subjective sleep diary measures, the Frost Multidimensional Perfectionism Scale (FMPS), Hewitt-Flett Multidimensional Perfectionism Scale (HFMPS) and Depression, Anxiety and Stress Scale 21 (DASS-21) were collected. RESULTS: High perfectionism levels were associated with poor sleep, but these relationships differed between objective and subjective measures. Perfectionism via FMPS total score and subscales of Concern over Mistakes, Doubts about Actions, Personal Standards and Self-oriented Perfectionism correlated with subjective sleep onset latency and sleep efficiency with moderate effects (r = .26 to .88). In contrast, perfectionism via HFMPS total score and subscales of Socially Prescribed Perfectionism and Parental Expectations predicted objective sleep onset latency and sleep efficiency. Additionally, stress mediated the relationships between objective sleep efficiency and Concern over Mistakes and Doubts about Actions. CONCLUSIONS: Perfectionism demonstrated stronger associations with subjective than objective sleep measures. Higher Parental Expectations and Socially Prescribed Perfectionism may increase one's vulnerability to objectively measured poor sleep. Therefore, perfectionism may be important in preventing and treating insomnia.

RAS and Other Molecular Targets in Pancreatic Cancer: The Next Wave Is Coming.

OPINION STATEMENT: Since the discovery of oncogenes in the 1970s, cancer doctors and researchers alike have understood the promise of discovering drugs to block the dominantly acting function of mutated signaling proteins in cancer. This promise was delivered, first slowly, with early signals inhibiting HER2 and BCR-Abl in the 1990s and 2000s, and then quickly, with kinase inhibitors being approved hand over fist in non-small cell lung cancer, melanoma, and many other malignancies. The RAS proteins, however, remained recalcitrant to chemical inhibition for decades, despite being, by far, the most frequently mutated oncogenes in cancers of all types. Nowhere was this deficit more palpable than in pancreatic ductal adenocarcinoma (PDA), where > 90% of cases are driven by single nucleotide substitutions at a single codon of the KRAS gene. The ice began to crack in 2012 when Ostrem and colleagues (Nature 503(7477): 548-551, 2013) synthesized the first KRAS G12C inhibitors, which covalently bind to GDP-bound G12C-mutated KRAS and lock the oncoprotein in its inactive state. In the last decade, the scientific community has established a new foundation on this and other druggable pockets in mutant KRAS. Here we provide an up-to-date overview of drugs targeting KRAS and other molecular targets in pancreatic cancer.

Childhood trauma is prevalent and associated with co-occurring depression, anxiety, mania and psychosis in young people attending Australian youth mental health services.

OBJECTIVES: Childhood trauma is common and associated with mental ill health. While high rates of trauma are observed across individual disorders, there is evidence that trauma is associated with an admixture of affective, anxiety and psychotic symptoms in adults. Given that early onset of mental disorder and trauma exposure herald poor outcomes, it is important to examine trauma prevalence rates in youth mental health services and to determine whether this trauma-related clustering is present in help-seeking young people. METHODS: We used data from the Transitions Study, a longitudinal investigation of young people attending headspace youth mental health services in Australia between January 2011 and August 2012. Participants were 775 young people aged 12-25. Childhood trauma was assessed using the Childhood Trauma Questionnaire. Multinomial regression was used to assess whether reported childhood trauma was more strongly associated with the co-occurrence of depression, anxiety, mania and psychosis symptoms than with any one in isolation. RESULTS: Approximately 84% of participants reported some form of abuse (emotional: 68%; physical: 32%; sexual: 22%) or neglect (emotional: 65%; physical: 46%). Exposure to multiple trauma types was common. Childhood trauma was significantly associated with each symptom domain. More severe childhood trauma was more strongly associated with the co-occurrence of symptoms than with any one symptom domain in isolation, such that more severely trauma-exposed young people were more likely to experience increased symptom clustering. CONCLUSIONS: Childhood trauma is pervasive in youth mental health services and associated with a symptom profile that cuts across traditional diagnostic boundaries.

FOLFIRI plus cetuximab or bevacizumab for advanced colorectal cancer: final survival and per-protocol analysis of FIRE-3, a randomised clinical trial.

BACKGROUND: Cetuximab plus FOLFIRI improved overall survival compared with bevacizumab plus FOLFIRI in KRAS wild-type metastatic colorectal cancer (mCRC) in FIRE-3, but no corresponding benefit was found for progression-free survival. This analysis aimed to determine whether cetuximab improves response and survival versus bevacizumab among response-evaluable patients receiving first-line FOLFIRI for RAS wild-type mCRC and the effect of primary tumour side on outcomes. METHODS: The intent-to-treat population included 593 patients with KRAS exon 2 wild-type mCRC. Further testing identified 400 patients with extended RAS wild-type disease; of these, 352 (88%) who received ≥3 cycles of therapy and had ≥1 post-baseline scan were evaluable for response and constituted the per-protocol population (169 cetuximab and 183 bevacizumab). Patients received 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) with either weekly cetuximab or biweekly bevacizumab given on day 1 of each 14-day cycle until response, progression or toxicity occurred. The primary endpoint was the objective response rate (ORR) in the per-protocol population. Secondary endpoints included overall survival (OS) and progression-free survival (PFS). The effect of primary tumour location was evaluated. RESULTS: Median OS in the RAS wild-type population was 31 vs 26 months in the cetuximab and bevacizumab groups, respectively (HR 0.76, P = 0.012). In the per-protocol population, outcomes favoured cetuximab for ORR (77% vs 65%, P = 0.014) and median OS (33 vs 26 months, HR 0.75, P = 0.011), while PFS was comparable between groups. The advantage of cetuximab over bevacizumab occurred only in patients with left-sided primary tumours. CONCLUSIONS: FOLFIRI plus cetuximab resulted in a significantly higher ORR and longer OS compared to FOLFIRI plus bevacizumab among patients with left-sided tumours. The superior response associated with cetuximab may particularly benefit patients with symptomatic tumours or borderline-resectable metastases. CLINICALTRIALS. GOV IDENTIFIER: NCT00433927.

Effect of a novel DNA vaccine against pancreas disease caused by salmonid alphavirus subtype 3 in Atlantic salmon (Salmo salar).

Pancreas disease (PD) caused by salmonid alphavirus subtype 3 (SAV3) is a serious disease with large economic impact on farmed Norwegian Atlantic salmon production despite years of use of oil-adjuvanted vaccines against PD (OAVs). In this study, two commercially available PD vaccines, a DNA vaccine (DNAV) and an OAV, were compared in an experimental setting. At approximately 1040° days (dd) at 12 °C post immunization, the fish were challenged with SAV3 by cohabitation 9 days after transfer to sea water. Sampling was done prior to challenge and at 19, 54, and 83 days post-challenge (dpc). When compared to the OAV and control (Saline) groups, the DNAV group had significantly higher SAV3 neutralizing antibody titers after the immunization period, significantly lower SAV3 viremia levels at 19 dpc, significantly reduced transmission of SAV3 to naïve fish in the latter part of the viremic phase, significantly higher weight gain post-challenge, and significantly reduced prevalence and/or severity of SAV-induced morphologic changes in target organs. The DNAV group had also significantly higher post-challenge survival compared to the Saline group, but not to the OAV group. The data suggest that use of DNAV may reduce the economic impact of PD by protecting against destruction of the pancreas tissue and subsequent growth impairment which is the most common and costly clinical outcome of this disease.

Cognitive strengths in first episode psychosis: a thematic analysis of clinicians' perspectives.

BACKGROUND: Cognitive deficits are associated with poor functional outcomes in individuals recovering from a first episode of psychosis (FEP). Existing treatments that target cognitive deficits in FEP may enhance cognitive function, but improvements to real-world functioning are less consistent. Furthermore, these treatments may not adequately address the personal recovery goals of young people attending FEP services. A novel cognitive strengths-based approach may overcome these shortcomings. METHODS: This qualitative study used semi-structured interviews to explore clinicians' (N = 12) perspectives toward the potential development of a cognitive strengths-based assessment or treatment in FEP. The interviews were analysed using thematic analysis. RESULTS: Five higher-order themes emerged: (1) pro-strengths attitude despite unfamiliarity and minimal use, (2) default to a cognitive deficit lens, (3) potential benefits of a cognitive strengths approach, (4) potential risks and barriers, and (5) considerations for successful implementation. While clinicians acknowledged their current deficit approach, they supported implementing a cognitive strengths assessment or treatment and highlighted their potential benefits for the personal recovery needs of young people with FEP. CONCLUSIONS: These findings suggest that a deficit-focused approach to cognitive function amongst clinicians may be common practice in FEP services. Nevertheless, a cognitive strengths approach was viewed favourably by clinicians and may represent a novel method of supporting personal recovery. Thus, the design and implementation of a cognitive strengths approach may be worthwhile. Future exploration of other stakeholder perspectives, such as young people with FEP, is essential.

Using Latent Class Analysis to Support the ICD-11 Complex Posttraumatic Stress Disorder Diagnosis in a Sample of Homeless Adults.

The 11th revision of the International Classification of Diseases (ICD-11), ratified at the World Health Assembly in May 2019, introduced revised diagnostic guidelines for posttraumatic stress disorder (PTSD) as well as a separate diagnosis of complex PTSD (CPTSD). We aimed to test the new ICD-11 symptom structure for PTSD and CPTSD in a sample of individuals who have experienced homelessness. Experiences of trauma exposure and the associated mental health outcomes have been underresearched in this population. A sample of adults experiencing homelessness (N = 206) completed structured and semi-structured interviews that collected information about trauma exposure and symptoms of PTSD and CPTSD. We conducted a latent class analysis (LCA) using six symptom clusters (three PTSD symptom clusters that are components of CPTSD and three CPTSD symptom clusters). All participants reported trauma exposure, with 88.6% having experienced at least one event before 16 years of age. Four distinct classes of participants emerged in relation to the potential to meet the diagnosis: LCA CPTSD (n = 122, 59.8%), LCA no diagnosis (n = 27: 13.2%), LCA PTSD (n = 33; 16.2%), and LCA disturbance in self-organization (DSO; n = 22; 10.8%). Of note, participants with an ICD-11 CPTSD as well as those with an ICD-11 PTSD diagnosis fell into the LCA CPTSD class. Our findings provide some support for the distinction between CPTSD and PTSD within this population specifically but potentially have broader implications. Clear diagnoses will allow targeted PTSD and CPTSD treatment development.

Depressive psychopathology in first-episode schizophrenia spectrum disorders: a systematic review, meta-analysis and meta-regression.

BACKGROUND: Despite knowing for many decades that depressive psychopathology is common in first-episode schizophrenia spectrum disorders (FES), there is limited knowledge regarding the extent and nature of such psychopathology (degree of comorbidity, caseness, severity) and its demographic, clinical, functional and treatment correlates. This study aimed to determine the pooled prevalence of depressive disorder and caseness, and the pooled mean severity of depressive symptoms, as well as the demographic, illness, functional and treatment correlates of depressive psychopathology in FES. METHODS: This systematic review, meta-analysis and meta-regression was prospectively registered (CRD42018084856) and conducted in accordance with PRISMA and MOOSE guidelines. RESULTS: Forty studies comprising 4041 participants were included. The pooled prevalence of depressive disorder and caseness was 26.0% (seven samples, N = 855, 95% CI 22.1-30.3) and 43.9% (11 samples, N = 1312, 95% CI 30.3-58.4), respectively. The pooled mean percentage of maximum depressive symptom severity was 25.1 (38 samples, N = 3180, 95% CI 21.49-28.68). Correlates of depressive psychopathology were also found. CONCLUSIONS: At least one-quarter of individuals with FES will experience, and therefore require treatment for, a full-threshold depressive disorder. Nearly half will experience levels of depressive symptoms that are severe enough to warrant diagnostic investigation and therefore clinical intervention - regardless of whether they actually fulfil diagnostic criteria for a depressive disorder. Depressive psychopathology is prominent in FES, manifesting not only as superimposed comorbidity, but also as an inextricable symptom domain.

Subjective experiences of neurocognitive functioning in young people with major depression.

BACKGROUND: Research suggests that young people with major depressive disorder (MDD) experience neurocognitive deficits and that these are associated with poorer functional and clinical outcomes. However, we are yet to understand how young people experience such difficulties. The aim of the current study was to explore the subjective experiences of neurocognitive functioning among young people with MDD. METHODS: Semi-structured qualitative interviews were conducted with 11 young people (aged 17-24 years) attending a specialist clinic for youth experiencing moderate-severe depression. Interview transcripts were analysed via Thematic Analysis to identify patterns and themes representing how young people with MDD subjectively experience neurocognitive deficits. RESULTS: Five main themes were identified: (1) experience of neurocognitive complaints; (2) relationship between neurocognitive complaints and depression; (3) impact on functioning; (4) strategies and supports; and (5) neurocognitive complaints and treatment. Overall, young people with MDD commonly experienced a range of subjective neurocognitive complaints. These appeared to have a bidirectional relationship with depressive symptomatology and significantly disrupted vocational, social and independent functioning, and aspects of psychological well-being including self-esteem. Neurocognitive difficulties represented an experiential barrier to psychological therapeutic engagement and were perceived as variably responsive to psychotropic medications, highlighting the need for targeted intervention. DISCUSSION: Neurocognitive difficulties are a common and pervasive experience for young people with MDD, with perceived impacts on depressive symptoms, attitudinal beliefs, everyday functioning and therapeutic engagement. Subjective neurocognitive complaints may therefore contribute to or exacerbate personal challenges faced by young people with MDD and thus, require early identification, consideration in psychological formulation, and treatment. Further research into the mechanisms of neurocognitive impairment in MDD is also needed.

Relevance of liver-limited disease in metastatic colorectal cancer: Subgroup findings of the FIRE-3/AIO KRK0306 trial.

In metastatic colorectal cancer (mCRC), liver-limited disease (LLD) is associated with a higher chance of metastectomy leading to long-term survival. However, limited data describes the prognostic and predictive relevance of initially unresectable LLD with regard to targeted first-line therapy. The present analysis investigated the relevance of initially unresectable LLD in mCRC patients treated with targeted therapy against either the epidermal growth factor receptor (EGFR) or vascular epithelial growth factor (VEGF). The analysis was performed based on FIRE-3, a randomized phase III trial comparing first-line chemotherapy with FOLFIRI plus either cetuximab (anti-EGFR) or bevacizumab (anti-VEGF) in RAS wild-type (WT) mCRC. Of 400 patients, 133 (33.3%) had LLD and 267 (66.8%) had non-LLD. Median overall survival (OS) was significantly longer in LLD compared to non-LLD patients (36.0 vs. 25.4 months; hazard ratio [HR] = 0.66; 95% confidence interval [CI]: 0.51-0.87; p = 0.002). In a multivariate analysis also including secondary hepatic resection as time-dependent variable, LLD status was independently prognostic for OS (HR = 0.67; 95% CI: 0.50-0.91; p = 0.01). As assessed by interaction tests, treatment benefit from FOLFIRI plus cetuximab compared to FOLFIRI plus bevacizumab was independent of LLD status with regard to objective response rate (ORR), early tumour shrinkage ≥20% (ETS), depth of response (DpR) and OS (all p > 0.05). In conclusion, LLD could be identified as a prognostic factor in RAS-WT mCRC, which was independent of hepatic resection in patients treated with targeted therapy. LLD had no predictive relevance since benefit from FOLFIRI plus cetuximab over bevacizumab was independent of LLD status.

Neurocognitive Functioning in Depressed Young People: A Systematic Review and Meta-Analysis.

BACKGROUND: Depression is among the most common mental health problems for young people. In adults, depression is associated with neurocognitive deficits that reduce the effectiveness of treatment and impair educational and vocational functioning. Compared to adults, less is known about the neurocognitive functioning of young people with depression, and existing research has reported inconsistent findings. METHOD: This systematic review and meta-analysis synthesized the literature on neurocognitive functioning in currently depressed youth aged 12-25 years in comparison to healthy controls. RESULTS: Following a systematic review of the literature, 23 studies were included in the meta-analysis. Poorer performance in the domains of attention (SMD: .50, 95% CI: .18-.83, p = .002), verbal memory (SMD: .78, 95% CI: .50-1.0, p < .001), visual memory (SMD: .65, 95% CI: .30-.99, p < .001), verbal reasoning/knowledge (SMD: .46; 95% CI: .14-.79; p < 0.001) and IQ (SMD: .32; 95% CI: .08-.56; p = 0.01) were identified in depressed youth. Relative weaknesses in processing speed/reaction time and verbal learning were also evident, however, these findings disappeared when the quality of studies was controlled for. Moderator analysis showed a tendency for poorer set-shifting ability in younger depressed participants relative to controls (although non-significant; p = .05). Moderator analysis of medication status showed taking medication was associated with poorer attentional functioning compared to those not taking medication. CONCLUSION: The findings suggest that currently depressed young people display a range of neurocognitive weaknesses which may impact treatment engagement and outcome. The findings support the need to consider neurocognitive functioning when treating youth with depression.

How family doctors perceived their 'readiness' and 'preparedness' to identify and respond to intimate partner abuse: a qualitative study.

Background: There are few existing studies which have investigated the meanings of 'readiness' and 'preparedness' among family doctors working with female patients who experience intimate partner abuse (IPA). Objectives: We aimed to explore how doctors perceived the concepts of readiness and preparedness to identify and respond to IPA against female patients. Methods: We adopted purposive sampling and conducted individual semi-structured interviews with 19 doctors (11 females and 8 males) practising in primary care. Thematic analysis identified dominant and associated themes, and the coding framework was transformed into a thematic map. We further applied cross-coding and code-confirming procedures in analysing the transcripts. Results: Participants described differences in the meanings of readiness and preparedness when responding to IPA, though they considered that these two concepts were inter-related. The findings revealed four themes of doctors' perceived 'readiness' to identify and respond to IPA: self-efficacy, emotional readiness, motivational readiness and attitudinal readiness, whereas doctors' perceived 'preparedness' comprise two themes: IPA knowledge and communication skills. Conclusion: Whether doctors are ready to identify and respond to IPA might be influenced by their emotional concerns as well as individual motivational beliefs and values, in addition to their attitudes and perceived self-efficacy, revealing a multidimensional concept. Besides enhancing doctors' preparedness by means of IPA knowledge and communication skills, training and IPA research could address further their emotional readiness and legitimize doctors' role to intervene in IPA cases.

The parental bonds of adolescent girls and next-generation maternal-infant bonding: findings from the Victorian Intergenerational Health Cohort Study.

The purpose of this study was to examine the extent to which adolescent bonding problems with parents predict next-generation maternal-infant bonding problems at 2 and 12 months postpartum. Data were from a two-generation prospective cohort study of 1026 offspring (3 perinatal waves) born to participants of a two-decade (10-wave) study of 1943 adolescents. Dyads in this analysis were 395 mothers (29-36 years) of 606 offspring (305 female). At 16 years, we assessed adolescents' perceptions of their mother's and father's care and control, separately and in combination. Subsequently, when participants were adult mothers of infants 2 and 12 months postpartum, we assessed impaired maternal-infant bonding, infant-directed rejection-anger, and caregiving anxiety. Adolescent-parent bonding problems were strongly predictive of women's subsequent bonding problems with infants. In particular, impaired postpartum maternal bonding was predicted by adolescent reports of low paternal care (12 months: OR=3.1, 95% CI 1.1-8.6) and high maternal control (12 months: OR=3.7, 95% CI 1.4-9.7). In combination, high maternal control and low paternal control also predicted impaired postpartum bonding (2 months: OR=5.0, 95% CI 1.3-20; 12 months: OR=12, 2.6-56), caregiving anxiety (2 months: OR=4, 95% CI 1.5-11; 12 months: OR=8.8, 95% CI 1.8-43), and rejection/anger (12 months: OR=4.1, 95% CI 1.0-16). Further combinations of care and overprotection that significantly predicted postpartum bonding problems are presented. Our results indicate that adolescent girls who experience high maternal control and low paternal care are at higher risk for subsequent maternal-infant bonding problems. The strength of associations suggests that interventions should begin well before pregnancy.

Use of Patient-reported Outcome Measures in Pediatric Orthopaedic Literature.

BACKGROUND: Patient-reported outcomes are increasingly used as primary measures of success and impact of health care services. There is no current consensus on the efficacy of functional health status (FHS) or health-related quality of life (HRQoL) evaluation in pediatric orthopaedic surgery. The purpose of this study was to quantify and characterize the use of such patient-reported outcomes in the pediatric orthopaedic literature over the last several years. METHODS: A cross-sectional review of 6 orthopaedic journals-Journal of Bone and Joint Surgery, Bone and Joint Journal, Spine, Journal of Pediatric Orthopaedics A, Journal of Pediatric Orthopaedics B, and Journal of Children's Orthopaedics, was conducted by 2 independent reviewers. Articles were analyzed for patient-reported outcome usage over the time periods of 2000 to 2001, 2007 to 2008, and 2012 to 2013. RESULTS: A total of 189 articles (2.7%) were identified that used patient-reported outcomes in pediatric populations. A total of 71 (37.5%) of these articles used FHS tools, 95 (50.3%) used HRQoL tools and 23 (12.2%) used a combination of both. The use of FHS and HRQoL tools has increased over time, with 8 FHS and 2 HRQoL publications in the year 2000 expanding to 19 and 28, respectively, in 2013. Journal of Bone and Joint Surgery American Volume published both the highest total number of articles containing patient-reported outcome measures (57/189) and the highest number of articles specifically using FHS measures (28/71). Spine published the highest number of articles using HRQoL measures (43/95). The most frequently used FHS and HRQoL tools were the Lysholm knee score and the Scoliosis Research Society tools, respectively. Only 33/73 identified patient-based outcome instruments had been validated in a pediatric population. CONCLUSIONS: Patient-reported outcome measures are underutilized in the pediatric orthopaedic literature. Instruments are frequently used that are neither designed nor validated for a pediatric population. Consequently, further work is necessary to develop, validate, and implement pediatric-specific FHS and HRQoL tools to fully understand the impact of a clinical intervention on all aspects of patient quality of life.

A possible dose-response association between distance to farmers' markets and roadside produce stands, frequency of shopping, fruit and vegetable consumption, and body mass index among customers in the Southern United States.

BACKGROUND: The association between farmers' market characteristics and consumer shopping habits remains unclear. Our objective was to examine associations among distance to farmers' markets, amenities within farmers' markets, frequency of farmers' market shopping, fruit and vegetable consumption, and body mass index (BMI). We hypothesized that the relationship between frequency of farmers' market shopping and BMI would be mediated by fruit and vegetable consumption. METHODS: In 15 farmers' markets in northeastern North Carolina, July-September 2015, we conducted a cross-sectional survey among 263 farmers' market customers (199 provided complete address data) and conducted farmers' market audits. To participate, customers had to be over 18 years of age, and English speaking. Dependent variables included farmers' market shopping frequency, fruit and vegetable consumption, and BMI. Analysis of variance, adjusted multinomial logistic regression, Poisson regression, and linear regression models, adjusted for age, race, sex, and education, were used to examine associations between distance to farmers' markets, amenities within farmers' markets, frequency of farmers' market shopping, fruit and vegetable consumption, and BMI. RESULTS: Those who reported shopping at farmers' markets a few times per year or less reported consuming 4.4 (standard deviation = 1.7) daily servings of fruits and vegetables, and those who reported shopping 2 or more times per week reported consuming 5.5 (2.2) daily servings. There was no association between farmers' market amenities, and shopping frequency or fruit and vegetable consumption. Those who shopped 2 or more times per week had a statistically significantly lower BMI than those who shopped less frequently. There was no evidence of mediation of the relationship between frequency of shopping and BMI by fruit and vegetable consumption. CONCLUSIONS: More work should be done to understand factors within farmers' markets that encourage fruit and vegetable purchases.

Ventricular volumes across stages of schizophrenia and other psychoses.

OBJECTIVE: Ventricular enlargement is common in established schizophrenia; however, data from ultra high-risk for psychosis and first-episode psychosis studies are inconclusive. This study aims to investigate ventricular volumes at different stages of psychosis. METHODS: Ventricular volumes were measured using a semi-automated and highly reliable method, for 89 established schizophrenia, 162 first-episode psychosis, 135 ultra high-risk for psychosis and 87 healthy controls using 1.5T magnetic resonance images. Clinical outcome diagnoses for ultra high-risk for psychosis were evaluated at long-term follow-up (mean: 7.5 years). RESULTS: Compared to controls, we identified significant ventricular enlargement of 36.2% in established schizophrenia ( p < 0.001). Ventricular enlargement was not significant in first-episode psychosis (6%) or ultra high-risk for psychosis (-3%). Examination across stages of schizophrenia-spectrum diagnoses subgroups revealed a significant linear trend ( p = 0.006; established schizophrenia = 36.2%, first-episode psychosis schizophrenia = 18.5%, first-episode psychosis schizophreniform = -4.2% and ultra high-risk for psychosis-schizophrenia converters = -18.5%). CONCLUSION: Ventricular enlargement is apparent in patients with established schizophrenia but is not a feature at the earliest stages of illness (ultra high-risk for psychosis and first-episode psychosis). Further research is needed to fully characterize the nature and timing of ventricular volume changes early in the course of illness and how these changes impact outcomes.

Antiglucocorticoid and related treatments for psychosis.

BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been implicated in the development and relapse of psychotic disorders. Elevated cortisol secretion has been positively linked with symptom severity in people with psychosis. Antiglucocorticoid and related drugs that target the HPA axis may be useful for the treatment of individuals with psychosis. OBJECTIVES: 1. To determine the effects of antiglucocorticoid and related drugs for the treatment of psychosis, when used alone or in combination with antipsychotic medication.2. To determine whether the effects of these medications differs between those in a prodromal phase or first episode of psychosis, and those with more established illness. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Trials Register (August 2009 and April 2014). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing antiglucocorticoid and related drugs compared to placebo (either as a sole treatment or as an adjunct to atypical antipsychotics, typical antipsychotics, antidepressants or other combination treatment) for people with a primary diagnosis of a psychotic disorder, or for individuals at high risk of developing a psychotic disorder. DATA COLLECTION AND ANALYSIS: Review authors independently selected trials, assessed methodological quality and extracted data. We used a fixed-effect meta-analysis. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes, and mean differences (MDs) and standardised mean differences (SMDs) with 95% CIs for continuous measures. We assessed risk of bias for included studies and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to create a 'Summary of findings' table. MAIN RESULTS: We included 11 studies that randomly assigned 509 people with schizophrenia, schizoaffective disorder or psychotic depression. No trials were conducted in patients at their first episode of psychotic illness and none included populations at high risk for developing psychosis. Our pre-stated outcomes of interest were mental state, global state, general functioning, adverse effects and quality of life.Two trials compared antiglucocorticoid drugs (mifepristone) versus placebo as sole treatment. Limited data from one trial showed no difference in the proportion responding to mifepristone when mental state was assessed immediately post intervention using the Brief Psychiatric Rating Scale (BPRS) (n = 5, 1 RCT, MD -5.20, 95% CI -17.91 to 7.51; very low-quality evidence); depressive symptoms (Hamilton Rating Scale for Depression (HAMD) total) were also similar between groups (n = 5, 1 RCT, MD 1.67, 95% CI -16.44 to 19.78; very low-quality evidence). However, a significant difference favoured treatment at short-term follow-up for global state (30% reduction in total BPRS, n = 221, 1 RCT, RR 0.58, 95% CI 0.38 to 0.89; low-grade quality evidence). This effect was also seen for short-term positive psychotic symptoms (50% reduction in BPRS positive symptom subscale, n = 221, 1 RCT, RR 0.60, 95% CI 0.43 to 0.84; low-grade quality evidence). Participants receiving mifepristone experienced a similar overall number of adverse effects as those receiving placebo (n = 226, 2 RCTs, RR 0.92, 95% CI 0.77 to 1.09; moderate-quality evidence). No data on general functioning or quality of life were available.One trial compared an antiglucocorticoid, dehydroepiandrosterone (DHEA), as an adjunct to atypical antipsychotic treatment to adjunctive placebo. Data for main outcomes of interest were of low quality, and analysis of useable data showed no significant effects of treatment on mental state or adverse effects. Data on global state, general functioning and quality of life were not available.Data from six trials comparing antiglucocorticoid drugs as an adjunct to combination treatment versus adjunctive placebo showed no significant differences between groups in mean endpoint scores for overall psychotic symptoms (n = 171, 6 RCTs, SMD 0.01, 95% CI - 0.29 to 0.32) or positive psychotic symptoms (n = 151, 5 RCTs, SMD -0.07, 95% CI - 0.40 to 0.25). Data from three trials showed no differences between groups in mean endpoint scores for negative symptoms (n = 94, 3 RCTs, MD 2.21, 95% CI -0.14 to 4.55). One study found improvements in global state that were similar between groups (n = 30, 1 RCT, RR 0.58, 95% CI 0.32 to 1.06; very low-quality evidence). In this comparison, pooled results showed that antiglucorticoids caused a greater overall number of adverse events (n = 199, 7 RCTs, RR 2.66, 95% CI 1.33 to 5.32; moderate quality evidence), but no quality of life data were available. AUTHORS' CONCLUSIONS: Good evidence is insufficient to conclude whether antiglucocorticoid drugs provide effective treatment for psychosis. Some global state findings suggest a favourable effect for mifepristone, and a few overall adverse effect findings favour placebo. Additional large randomised controlled trials are needed to justify findings.

In the End It All Makes Sense: Meaning in Life at Either End of the Adult Lifespan.

This study explored psychological well-being in Australian adults with a particular focus on meaning in life. Older adults (N = 57) reported lower levels of search for meaning and higher levels of presence of meaning than young adults (N = 208) suggesting that both groups were able to distinguish between the two aspects of meaning. For older adults, higher presence was associated with better mental health and well-being outcomes, regardless of level of search. For the young adults, higher presence and lower search was associated with better outcomes. These results suggest that presence of meaning is an important aspect of well-being for older adults living in a high income English-speaking country and may be an important focus when working with depressed or anxious older adults, while both presence of, and search for meaning may be more meaningful therapeutic targets when working with depressed or anxious younger adults. Theoretical implications are discussed.

Rumination, depressive symptoms and awareness of illness in schizophrenia.

BACKGROUND: Depressive symptoms are common in schizophrenia. Previous studies have observed that depressive symptoms are associated with both insight and negative appraisals of illness, suggesting that the way in which the person thinks about their illness may influence the occurrence of depressive responses. In affective disorders, one of the most well-established cognitive processes associated with depressive symptoms is rumination, a pattern of perseverative, self-focused negative thinking. AIMS: This study examined whether rumination focused on mental illness was predictive of depressive symptoms during the subacute phase of schizophrenia. METHOD: Forty participants with a diagnosis of schizophrenia and in a stable phase of illness completed measures of rumination, depressive symptoms, awareness of illness, and positive and negative symptoms. RESULTS: Depressive symptoms were correlated with rumination, including when controlling for positive and negative symptoms. The content of rumination frequently focused on mental illness and its causes and consequences, in particular social disability and disadvantage. Depressive symptoms were predicted by awareness of the social consequences of mental illness, an effect that was mediated by rumination. CONCLUSIONS: Results suggest that a process of perseveratively dwelling upon mental illness and its social consequences may be a factor contributing to depressive symptoms in people with chronic schizophrenia.

Development and validation of the positive evaluation core beliefs scale for social anxiety.

Fear of positive evaluation (FPE) is becoming recognised as an important component of social anxiety that is distinct from fear of negative evaluation (FNE). While core belief scales exist for fear of negative evaluation (FNE), none has been developed for FPE. Therefore, this paper describes the development and validation of a measure of core beliefs that is specific to FPE. An exploratory factor analysis was performed on 60 initial items with an Australian undergraduate sample, in which a confirmatory factor analysis was performed with an independent Australian general population sample. A series of further analyses were performed to test convergent and divergent validity. The Positive Evaluation Core Beliefs Scale (PECS) emerged as a 17-item two-factor psychometrically valid measure that correlates more strongly with measurement of FPE than FNE. The PECS measure offers a new opportunity for researchers and clinicians to better explore cognitions associated with social anxiety.