Perinatal Western-style diet exposure associated with decreased microglial counts throughout the arcuate nucleus of the hypothalamus in Japanese macaques.

Perinatal exposure to a high-fat, high-sugar Western-style diet (WSD) is associated with altered neural circuitry in the melanocortin system. This association may have an underlying inflammatory component, as consumption of a WSD during pregnancy can lead to an elevated inflammatory environment. Our group previously demonstrated that prenatal WSD exposure was associated with increased markers of inflammation in the placenta and fetal hypothalamus in Japanese macaques. In this follow-up study, we sought to determine whether this heightened inflammatory state persisted into the postnatal period, as prenatal exposure to inflammation has been shown to reprogram offspring immune function and long-term neuroinflammation would present a potential means for prolonged disruptions to microglia-mediated neuronal circuit formation. Neuroinflammation was approximated in 1-yr-old offspring by counting resident microglia and peripherally derived macrophages in the region of the hypothalamus examined in the fetal study, the arcuate nucleus (ARC). Microglia and macrophages were immunofluorescently stained with their shared marker, ionized calcium-binding adapter molecule 1 (Iba1), and quantified in 11 regions along the rostral-caudal axis of the ARC. A mixed-effects model revealed main effects of perinatal diet (P = 0.011) and spatial location (P = 0.003) on Iba1-stained cell count. Perinatal WSD exposure was associated with a slight decrease in the number of Iba1-stained cells, and cells were more densely located in the center of the ARC. These findings suggest that the heightened inflammatory state experienced in utero does not persist postnatally. This inflammatory response trajectory could have important implications for understanding how neurodevelopmental disorders progress.NEW & NOTEWORTHY Prenatal Western-style diet exposure is associated with increased microglial activity in utero. However, we found a potentially neuroprotective reduction in microglia count during early postnatal development. This trajectory could inform the timing of disruptions to microglia-mediated neuronal circuit formation. Additionally, this is the first study in juvenile macaques to characterize the distribution of microglia along the rostral-caudal axis of the arcuate nucleus of the hypothalamus. Nearby neuronal populations may be greater targets during inflammatory insults.

Direct Measurement of Hexacontatetrapole, E6 γ Decay from

The only proposed observation of a discrete, hexacontatetrapole (E6) transition in nature occurs from the T_{1/2}=2.54(2)-min decay of ^{53m}Fe. However, there are conflicting claims concerning its γ-decay branching ratio, and a rigorous interrogation of γ-ray sum contributions is lacking. Experiments performed at the Australian Heavy Ion Accelerator Facility were used to study the decay of ^{53m}Fe. For the first time, sum-coincidence contributions to the weak E6 and M5 decay branches have been firmly quantified using complementary experimental and computational methods. Agreement across the different approaches confirms the existence of the real E6 transition; the M5 branching ratio and transition rate have also been revised. Shell model calculations performed in the full fp model space suggest that the effective proton charge for high-multipole, E4 and E6, transitions is quenched to approximately two-thirds of the collective E2 value. Correlations between nucleons may offer an explanation of this unexpected phenomenon, which is in stark contrast to the collective nature of lower-multipole, electric transitions observed in atomic nuclei.

Early-in-life isoflurane exposure alters resting-state functional connectivity in juvenile non-human primates.

BACKGROUND: Clinical studies suggest that anaesthesia exposure early in life affects neurobehavioural development. We designed a non-human primate (NHP) study to evaluate cognitive, behavioural, and brain functional and structural alterations after isoflurane exposure during infancy. These NHPs displayed decreased close social behaviour and increased astrogliosis in specific brain regions, most notably in the amygdala. Here we hypothesise that resting-state functional connectivity MRI can detect alterations in connectivity of brain areas that relate to these social behaviours and astrogliosis. METHODS: Imaging was performed in 2-yr-old NHPs under light anaesthesia, after early-in-life (postnatal days 6-12) exposure to 5 h of isoflurane either one or three times, or to room air. Brain images were segmented into 82 regions of interest; the amygdala and the posterior cingulate cortex were chosen for a seed-based resting-state functional connectivity MRI analysis. RESULTS: We found differences between groups in resting-state functional connectivity of the amygdala and the auditory cortices, medial premotor cortex, and posterior cingulate cortex. There were also alterations in resting-state functional connectivity between the posterior cingulate cortex and secondary auditory, polar prefrontal, and temporal cortices, and the anterior insula. Relationships were identified between resting-state functional connectivity alterations and the decrease in close social behaviour and increased astrogliosis. CONCLUSIONS: Early-in-life anaesthesia exposure in NHPs is associated with resting-state functional connectivity alterations of the amygdala and the posterior cingulate cortex with other brain regions, evident at the juvenile age of 2 yr. These changes in resting-state functional connectivity correlate with the decrease in close social behaviour and increased astrogliosis. Using resting-state functional connectivity MRI to study the neuronal underpinnings of early-in-life anaesthesia-induced behavioural alterations could facilitate development of a biomarker for anaesthesia-induced developmental neurotoxicity.

Structural features of subchondral bone cysts and adjacent tissues in hip osteoarthritis.

OBJECTIVE: Focal lesions within the subchondral bone, termed subchondral bone cysts (SBCs), are clinically accepted radiographic markers of advanced osteoarthritis (OA), but their etiology in the hip is not well understood. DESIGN: This study used micro-computed tomography (µCT), and histological and immunocytological analysis to examine the prevalence, size, location, and morphological and cellular features of SBCs found within 34 femoral heads (14 male, 20 female; age range = 43-80 years) obtained from total hip arthroplasty procedures. RESULTS: SBCs were common-present in 91% of the femoral heads examined-and frequently commuted with the surface of the femoral head, but otherwise showed no preferred anatomical location. Few associations were found between SBC features and patient characteristics such as BMI, age and sex. SBCs were also heterogenous in composition, ranging from fibrous (most common) to predominantly fatty (least common) and often containing vasculature, nerve fibers, cartilage islands, and bony spicules. Despite this heterogeneity, focal abnormalities in bone density and cartilage thickness were consistently observed. Bone adjacent to SBCs was denser than that in the primary compressive group, and cartilage thickness in regions overlying SBCs was lower than in non-overlying regions. In contrast to these local bony changes, µCT-based finite element analyses indicated that the stiffness of the primary compressive group was only mildly affected by SBCs. CONCLUSIONS: These findings indicate that SBCs in the femoral head involve extensive perturbations in cellular activity, culminating in myriad skeletal tissue types and spatially heterogenous changes in bone and cartilage morphology that are likely to affect OA progression.

Electric Monopole Transition from the Superdeformed Band in

The electric monopole (E0) transition strength ρ^{2} for the transition connecting the third 0^{+} level, a "superdeformed" band head, to the "spherical" 0^{+} ground state in doubly magic ^{40}Ca is determined via e^{+}e^{-} pair-conversion spectroscopy. The measured value ρ^{2}(E0;0_{3}^{+}→0_{1}^{+})=2.3(5)×10^{-3} is the smallest ρ^{2}(E0;0^{+}→0^{+}) found in A<50 nuclei. In contrast, the E0 transition strength to the ground state observed from the second 0^{+} state, a band head of "normal" deformation, is an order of magnitude larger ρ^{2}(E0;0_{2}^{+}→0_{1}^{+})=25.9(16)×10^{-3}, which shows significant mixing between these two states. Large-scale shell-model (LSSM) calculations are performed to understand the microscopic structure of the excited states and the configuration mixing between them; experimental ρ^{2} values in ^{40}Ca and neighboring isotopes are well reproduced by the LSSM calculations. The unusually small ρ^{2}(E0;0_{3}^{+}→0_{1}^{+}) value is due to destructive interference in the mixing of shape-coexisting structures, which are based on several different multiparticle-multihole excitations. This observation goes beyond the usual treatment of E0 strengths, where two-state shape mixing cannot result in destructive interference.

Quenching of Single-Particle Strength in A=15 Nuclei.

Absolute cross sections for the addition of s- and d-wave neutrons to ^{14}C and ^{14}N have been determined simultaneously via the (d,p) reaction at 10 MeV/u. The difference between the neutron and proton separation energies, ΔS, is around -20 MeV for the ^{14}C+n system and +8 MeV for ^{14}N+n. The population of the 1s_{1/2} and 0d_{5/2} orbitals for both systems is reduced by a factor of approximately 0.5 compared with the independent single-particle model, or about 0.6 when compared with the shell model. This finding strongly contrasts with results deduced from intermediate-energy knockout reactions between similar nuclei on targets of ^{9}Be and ^{12}C. The simultaneous technique used removes many systematic uncertainties.

Maternal diet and obesity shape offspring central and peripheral inflammatory outcomes in juvenile non-human primates.

The obesity epidemic affects 40% of adults in the US, with approximately one-third of pregnant women classified as obese. Previous research suggests that children born to obese mothers are at increased risk for a number of health conditions. The mechanisms behind this increased risk are poorly understood. Increased exposure to in-utero inflammation induced by maternal obesity is proposed as an underlying mechanism for neurodevelopmental alterations in offspring. Utilizing a non-human primate model of maternal obesity, we hypothesized that maternal consumption of an obesogenic diet will predict offspring peripheral (e.g., cytokines and chemokines) and central (microglia number) inflammatory outcomes via the diet's effects on maternal adiposity and maternal inflammatory state during the third trimester. We used structural equation modeling to simultaneously examine the complex associations among maternal diet, metabolic state, adiposity, inflammation, and offspring central and peripheral inflammation. Four latent variables were created to capture maternal chemokines and pro-inflammatory cytokines, and offspring cytokine and chemokines. Model results showed that offspring microglia counts in the basolateral amygdala were associated with maternal diet (ß = -0.622, p < 0.01), adiposity (ß = 0.593, p < 0.01), and length of gestation (ß = 0.164, p < 0.05) but not with maternal chemokines (ß = 0.135, p = 0.528) or maternal pro-inflammatory cytokines (ß = 0.083, p = 0.683). Additionally, we found that juvenile offspring peripheral cytokines (ß = -0.389, p < 0.01) and chemokines (ß = -0.298, p < 0.05) were associated with a maternal adiposity-induced decrease in maternal circulating chemokines during the third trimester (ß = -0.426, p < 0.01). In summary, these data suggest that maternal diet and adiposity appear to directly predict offspring amygdala microglial counts while maternal adiposity influences offspring peripheral inflammatory outcomes via maternal inflammatory state.

Maternal Western-style diet reduces social engagement and increases idiosyncratic behavior in Japanese macaque offspring.

Recent evidence in humans and animals indicates an association between maternal obesity and offspring behavioral outcomes. In humans, increased maternal body mass index has been linked to an increased risk of children receiving a diagnosis of early-emerging neurodevelopmental disorders such as Attention Deficit/Hyperactivity Disorder (ADHD) and/or Autism Spectrum Disorder (ASD). However, a limited number of preclinical studies have examined associations between maternal Western-Style Diet (mWSD) exposure and offspring social behavior. To our knowledge, this is the first study to investigate relationships between mWSD exposure and social behavior in non-human primates. Since aberrant social behavior is a diagnostic criterion for several neurodevelopmental disorders, the current study focuses on examining the influence of maternal nutrition and metabolic state on offspring social behavior in Japanese macaques (Macaca fuscata). We found that mWSD offspring initiated less affiliative social behaviors as well as proximity to a peer. Using path analysis, we found that the association between mWSD consumption and reduced offspring social engagement was statistically mediated by increased maternal interleukin (IL)-12 during the third trimester of pregnancy. Additionally, mWSD offspring displayed increased idiosyncratic behavior, which was related to alterations in maternal adiposity and leptin in the third trimester. Together, these results suggest that NHP offspring exposed to mWSD exhibit behavioral phenotypes similar to what is described in some early-emerging neurodevelopmental disorders. These results provide evidence that mWSD exposure during gestation may be linked to increased risk of neurodevelopmental disorders and provides targets for prevention and intervention efforts.

High pressure frozen oocytes have improved ultrastructure but reduced cleavage rates compared to conventionally fixed or vitrified oocytes.

CONTEXT: Live birth rates are lower for cryopreserved oocytes than for fresh IVF cycles, indicating a need for improved methodologies. AIMS: The aim of this study was to determine if high pressure freezing (HPF) could improve both ultrastructural preservation and cryopreserved oocyte quality when compared to conventional fixation and vitrification methods. METHODS: Sheep oocytes and embryos were prepared by HPF or vitrification, with or without cryoprotectants. Frozen oocytes were prepared for transmission electron microscopy or warmed, in vitro fertilised and the recovery and cleavage rates recorded. KEY RESULTS: Blastocyst rates were similar between fresh, HPF and vitrified embryos. HPF oocytes had improved ultrastructure compared to conventional fixation or vitrification, but had poorer survival and cleavage rates compared to vitrified oocytes. Freeze-substitution of cryopreserved oocytes and transmission electron microscopy demonstrated disruption of the oocyte ultrastructure in the presence of cryoprotectants. CONCLUSIONS: Superior preservation of ultrastructure was observed in HPF oocytes compared to vitrification or conventional fixation methods. In the presence of CP, both embryos and oocytes could survive HPF and warming but oocytes had reduced development. IMPLICATIONS: The HPF method has potential to be developed and lead to improved oocyte and embryo cryopreservation and outcomes for assisted reproduction.

Depression and physical health multimorbidity: primary data and country-wide meta-analysis of population data from 190 593 people across 43 low- and middle-income countries.

BACKGROUND: Despite the known heightened risk and burden of various somatic diseases in people with depression, very little is known about physical health multimorbidity (i.e. two or more physical health co-morbidities) in individuals with depression. This study explored physical health multimorbidity in people with clinical depression, subsyndromal depression and brief depressive episode across 43 low- and middle-income countries (LMICs). METHOD: Cross-sectional, community-based data on 190 593 individuals from 43 LMICs recruited via the World Health Survey were analysed. Multivariable logistic regression analysis was done to assess the association between depression and physical multimorbidity. RESULTS: Overall, two, three and four or more physical health conditions were present in 7.4, 2.4 and 0.9% of non-depressive individuals compared with 17.7, 9.1 and 4.9% among people with any depressive episode, respectively. Compared with those with no depression, subsyndromal depression, brief depressive episode and depressive episode were significantly associated with 2.62, 2.14 and 3.44 times higher odds for multimorbidity, respectively. A significant positive association between multimorbidity and any depression was observed across 42 of the 43 countries, with particularly high odds ratios (ORs) in China (OR 8.84), Laos (OR 5.08), Ethiopia (OR 4.99), the Philippines (OR 4.81) and Malaysia (OR 4.58). The pooled OR for multimorbidity and depression estimated by meta-analysis across 43 countries was 3.26 (95% confident interval 2.98-3.57). CONCLUSIONS: Our large multinational study demonstrates that physical health multimorbidity is increased across the depression spectrum. Public health interventions are required to address this global health problem.

Depressive spectrum disorders in cancer: prevalence, risk factors and screening for depression: a critical review.

BACKGROUND: Although depression and mood-related disorders are common in persons with cancer, these conditions remain frequently overlooked in clinical practice. Negative consequences of depressive disorder spectrum have been reported (e.g. suicidal ideation, increase physical complications and somatic symptoms, negative influence on prognosis), indicating the need for routine screening, assessment and management. METHODS: A search of the major databases (Medline, Embase, PsycLIT, PsycINFO, and the Cochrane Library) was conducted on the reviews and meta-analyses available in order to summarize relevant data concerning depressive disorders spectrum in terms of prevalence, risk factors, and screening and assessment among patients with cancer across the trajectory of the disease. RESULTS: The data show a prevalence of depression and depressive disorders between 5% and 60% according to the different diagnostic criteria, the tools used in the studies (e.g. semi-structured psychiatric interview and psychometric questionnaires), as well as the stage and type of cancer. Furthermore, despite the significant health care resources devoted to cancer care and the importance of addressing depressive symptoms, assessment and management of depressive spectrum disorders in cancer patients remains suboptimal. CONCLUSIONS: Routine screening and adequate assessment of depressive spectrum disorders is necessary in patients with cancer in order to effectively manage the multifaceted and complex consequences on cancer care.

Relationship between prolactin, breast cancer risk, and antipsychotics in patients with schizophrenia: a critical review.

OBJECTIVE: A recent meta-analysis showed that breast cancer probably is more common in female patients with schizophrenia than in the general population (effect size = 1.25, P < 0.05). Increasing experimental and epidemiological data have alerted researchers to the influence of prolactin (PRL) in mammary carcinogenesis. We therefore investigated the possible relationship between antipsychotic-induced hyperprolactinemia (HPRL) and breast cancer risk in female patients with schizophrenia. METHOD: A literature search (1950 until January 2015), using the MEDLINE database, was conducted for English-language published clinical trials to identify and synthesize data of the current state of knowledge concerning breast cancer risk (factors) in women with schizophrenia and its (their) relationship between HPRL and antipsychotic medication. RESULTS: Although an increasing body of evidence supports the involvement of PRL in breast carcinogenesis, results of human prospective studies are limited, equivocal, and correlative (with risk ratios ranging from 0.70 to 1.9 for premenopausal women and from 0.76 to 2.03 for postmenopausal women). Moreover, these studies equally do not take into account the local production of PRL in breast epithelium, although amplification or overexpression of the local autocrine/paracrine PRL loop may be a more important mechanism in tumorigenesis. Until now, there is also no conclusive evidence that antipsychotic medication can increase the risk of breast malignancy and mortality. CONCLUSION: Other breast risk factors than PRL, such as nulliparity, obesity, diabetes mellitus, and unhealthy lifestyle behaviours (alcohol dependence, smoking, low physical activity), probably are of greater relevance in individual breast cancer cases within the population of female patients with schizophrenia.

Reliability and Determinants of Self-Evaluation of Breathing Questionnaire (SEBQ) Score: A Symptoms-Based Measure of Dysfunctional Breathing.

Dysfunctional breathing is characterised by an abnormal breathing pattern leading to respiratory symptoms. The 25-item Self Evaluation of Breathing Questionnaire (SEBQ) has been developed to measure breathing-related symptoms and their severity but lacks thorough evaluation. To determine reproducibility, internal consistency and predictors of SEBQ score, 180 participants completed an online SEBQ with additional demographic and lifestyle questions. Two weeks later, 155 of those repeated SEBQ. Test-retest correlation of the SEBQ was high [intraclass correlation coefficient (3, 1) = 0.89; 95 % CI 0.85-0.92]. There was no difference in SEBQ score between test and retest (15.1 (11.6) [mean (SD)] versus 14.7 (12.4); P = 0.4) and the score showed a typical error (standard error of measurement) of 4.0. Internal consistency was high (Cronbach's α = 0.93), and a single factor structure for items was shown. Smoking status, reported respiratory disease, recent respiratory illness and female gender were positively-associated predictors of SEBQ score, and together explained 25.6 % of score variance (P ≤ 0.001). The SEBQ has high test-retest reproducibility and its score may be predicted by current smoking, chronic respiratory disease, recent respiratory illness and female gender, thus may be a useful clinical screening tool for dysfunctional breathing.

The prevalence and predictors of type two diabetes mellitus in people with schizophrenia: a systematic review and comparative meta-analysis.

OBJECTIVE: To conduct a meta-analysis investigating the prevalence of type two diabetes mellitus (T2DM) in people with schizophrenia compared to controls. METHOD: Systematic review of electronic databases from inception till November 2014. Articles reporting the prevalence of T2DM in people with schizophrenia and healthy controls (without mental illness) were included. Two independent authors conducted searches and extracted data. A random effects relative risks (RR) meta-analysis was conducted. RESULTS: Twenty-five studies including 145,718 individuals with schizophrenia (22.5-54.4 years) and 4,343,407 controls were included. The prevalence of T2DM in people with schizophrenia was 9.5% (95% CI = 7.0-12.8, n = 145,718) and 10.75% (95% CI 7.44-14.5%, n = 2698) in studies capturing T2DM according to recognized criteria. The pooled RR across all studies was 1.82 (95% CI = 1.56-2.13; = 4,489,125). Subgroup analyses found a RR of 2.53 (95% CI = 1.68-3.799, n = 17,727) in studies ascertaining T2DM according to recognized criteria and RR 1.65 (95% CI = 1.34-2.03, n = 4,243,389) in studies relying on T2DM determined through medical records. CONCLUSION: People with schizophrenia are at least double the risk of developing T2DM according to recognized T2DM criteria. Proactive lifestyle and screening programmes should be given clinical priority.

Promoting physical health for people with schizophrenia by reducing disparities in medical and dental care.

OBJECTIVE: Acquiring a diagnosis of schizophrenia reduces life expectancy for many reasons including poverty, difficulties in communication, side-effects of medication and access to care. This mortality gap is driven by natural deaths; cardiovascular disease is a major cause, but outcomes for people with severe mental illness are worse for many physical health conditions, including cancer, fractures and complications of surgery. We set out to examine the literature on disparities in medical and dental care experienced by people with schizophrenia and suggest possible approaches to improving health. METHOD: This narrative review used a targeted literature search to identify the literature on physical health disparities in schizophrenia. RESULTS: There is evidence of inequitable access to and/or uptake of physical and dental health care by those with schizophrenia. CONCLUSION: The goal was to reduce the mortality gap through equity of access to all levels of health care, including acute care, long-term condition management, preventative medicine and health promotion. We suggest solutions to promote health, wellbeing and longevity in this population, prioritising identification of and intervention for risk factors for premature morbidity and mortality. Shared approaches are vital, while joint education of clinicians will help break down the artificial mind-body divide.

How can we promote smoking cessation in people with schizophrenia in practice? A clinical overview.

OBJECTIVE: High rates of smoking and nicotine dependence are associated with increased physical comorbidity and premature death in people with schizophrenia. We conducted a clinical overview to establish how smoking cessation should be promoted in practice. METHOD: Systematic clinical review of major electronic databases from inception till November 2014. RESULTS: A growing body of evidence supports pharmacological interventions to assist smoking cessation. The most promising evidence is for bupropion with several meta-analyses demonstrating its effectiveness. Currently, there is limited evidence demonstrating the effectiveness of nicotine replacement therapy (NRT) and varenicline, although this is likely to be due to the paucity of research. There are no consistent data to suggest that pharmacological interventions increase adverse events. Behavioural and psychosocial interventions also demonstrate promise, particularly when combined with pharmacotherapy. Careful monitoring of antipsychotic levels (in particular clozapine) is essential, and the promotion of physical activity may be useful to negate potential weight gain and diabetes risk following smoking cessation. CONCLUSION: Evidence from systematic reviews and meta-analyses suggests that smoking cessation interventions are effective in people with schizophrenia, although more long-term research is required. Promoting smoking cessation should be given utmost priority in clinical practice, and we offer practical strategies to facilitate this.

Promotion of cardiorespiratory fitness in schizophrenia: a clinical overview and meta-analysis.

OBJECTIVE: Cardiorespiratory fitness (CRF) is a major modifiable risk factor for cardiovascular disease (CVD). We conducted a clinical overview to highlight the reduced CRF expressed as maximal oxygen uptake (VO2max) (or predicted) or peak oxygen uptake (VO2 peak) in people with schizophrenia compared to the general population. We also aimed to identify correlates of and clinical strategies to improve CRF. METHOD: We systematically searched major electronic databases from inception until November 2014. A meta-analysis calculating the standardised mean difference (SMD) was employed. RESULTS: CRF was significantly reduced in people with schizophrenia (n = 154) with a SMD of -0.96 (95% CI -1.29 to -0.64) (N = 5) compared to controls (n = 182). Negative symptoms, increased body mass index and female gender were negatively associated with CRF. Promoting physical activity may improve CRF in people with schizophrenia by up to 4-4.5 ml/kg/min following a 6-8 weeks programme (N = 4, n = 98). CONCLUSION: People with schizophrenia have a large and significantly reduced CRF. Given the overwhelming evidence for physical activity as the cornerstone of preventing and managing CVD in the general population, incorporating such interventions in the treatment of people with schizophrenia is justified and urgently required. We present clear practical strategies of how this can be achieved within clinical settings.

The prevalence of pain in bipolar disorder: a systematic review and large-scale meta-analysis.

OBJECTIVE: To conduct a meta-analysis investigating the prevalence of pain in people with bipolar disorder (BD). METHOD: A systematic review and random effects meta-analysis searching major electronic databases from inception till 01/2014 in accordance with the PRISMA statement. We included articles reporting quantitative data on the prevalence of pain in people with BD with or without a healthy control group. Two independent authors conducted searches, extracted data, and completed methodological quality assessment. RESULTS: Twenty two cross-sectional studies were included, representing 12,375,644 individuals (BD n=171,352, n controls=12,204,292). The prevalence of pain in people with BD was 28.9% (95% CI=16.4-43.4%, BD n=171,352). The relative risk (RR) of pain in BD compared to controls was 2.14 (95% CI=1.67-2.75%, n=12,342,577). The prevalence of migraine was 14.2% (95% CI=10.6-18.3%, BD n=127,905), and the RR was 3.30 (95% CI=2.27-4.80%, n=6,732,220).About 23.7% (95% CI=13.1-36.3%, n=106,214) of people with BD experienced chronic pain. Age, percentage of males, methodological quality, and method of BD classification did not explain the observed heterogeneity. CONCLUSION: People with BD experience significantly increased levels of pain (particularly chronic pain and migraine). The assessment and treatment of pain should form an integral part of the management of BD.

Metabolic syndrome and metabolic abnormalities in patients with major depressive disorder: a meta-analysis of prevalences and moderating variables.

BACKGROUND: Individuals with depression have an elevated risk of cardiovascular disease (CVD) and metabolic syndrome (MetS) is an important risk factor for CVD. We aimed to clarify the prevalence and correlates of MetS in persons with robustly defined major depressive disorder (MDD). METHOD: We searched Medline, PsycINFO, EMBASE and CINAHL up until June 2013 for studies reporting MetS prevalences in individuals with MDD. Medical subject headings 'metabolic' OR 'diabetes' or 'cardiovascular' or 'blood pressure' or 'glucose' or 'lipid' AND 'depression' OR 'depressive' were used in the title, abstract or index term fields. Manual searches were conducted using reference lists from identified articles. RESULTS: The initial electronic database search resulted in 91 valid hits. From candidate publications following exclusions, our search generated 18 studies with interview-defined depression (n = 5531, 38.9% male, mean age = 45.5 years). The overall proportion with MetS was 30.5% [95% confidence interval (CI) 26.3-35.1] using any standardized MetS criteria. Compared with age- and gender-matched control groups, individuals with MDD had a higher MetS prevalence [odds ratio (OR) 1.54, 95% CI 1.21-1.97, p = 0.001]. They also had a higher risk for hyperglycemia (OR 1.33, 95% CI 1.03-1.73, p = 0.03) and hypertriglyceridemia (OR 1.17, 95% CI 1.04-1.30, p = 0.008). Antipsychotic use (p < 0.05) significantly explained higher MetS prevalence estimates in MDD. Differences in MetS prevalences were not moderated by age, gender, geographical area, smoking, antidepressant use, presence of psychiatric co-morbidity, and median year of data collection. CONCLUSIONS: The present findings strongly indicate that persons with MDD are a high-risk group for MetS and related cardiovascular morbidity and mortality. MetS risk may be highest in those prescribed antipsychotics.

Cause of death in mild cognitive impairment: a prospective study (NEDICES).

BACKGROUND AND PURPOSE: Previous studies have reported the occurrence of increased mortality rates among individuals with mild cognitive impairment (MCI), but possible links between MCI subtypes and cause-specific mortality need to be explored. To examine short-term mortality (5 years), long-term mortality (13 years) and cause-specific mortality of individuals over 65 years of age suffering from MCI compared with cognitively unimpaired individuals in the Neurological Disorders in Central Spain (NEDICES) cohort. METHODS: Mild cognitive impairment was classified using standardized psychometric and functional assessment in accordance with diagnostic convention. Cox's proportional hazards models, adjusted by sociodemographics and comorbidity factors, were used to assess the risk of death at 5 and 13 years of MCI subtypes compared with a reference group of older people without cognitive impairment (N = 2329). Causes of death were obtained from the National Population Register of Spain. RESULTS: There were 1484 deceased individuals at 13 years. MCI subtypes were defined as amnestic single domain (N = 259), amnestic multiple domain (N = 197) and non-amnestic (N = 641). After adjusting for covariates, only the amnestic multiple domain MCI subtype showed an increased hazard ratio (HR) for mortality at 5 years versus the reference group. However, the HR for mortality at 13 years was increased for all MCI subtypes. The HR by MCI subtype was 1.19 in the non-amnestic subtype (95% CI 1.05-1.36), 1.31 in the amnestic single domain subtype (95% CI 1.10-1.56) and 1.67 in the amnestic multiple domain subtype (95% CI 1.38-2.02). In terms of cause-specific mortality, the chance of death from dementia was statistically higher in all MCI subtypes. CONCLUSION: Amnestic multiple domain MCI showed the greatest risk of mortality in comparison with other MCI subtypes at different intervals. Dementia was the only cause-specific mortality that was increased in MCI individuals.