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Background: Mitochondrial dysfunction is implicated in the neuropathology of bipolar disorder (BD). Higher circulating cell-free mitochondrial DNA (ccf-mtDNA), generally reflecting poorer mitochondrial health, has been associated with greater symptoms severity in BD. The current study examines the association of serum ccf-mtDNA and brain structure in relation to youth BD. We hypothesized that higher ccf-mtDNA will be associated with measures of lower brain structure, particularly in the BD group. Methods: Participants included 40 youth (BD, n = 19; Control group [CG], n = 21; aged 13–20 years). Serum ccf-mtDNA levels were assayed. T1-weighted brain images were acquired using 3T-MRI. Region of interest (ROI) analyses examined prefrontal cortex (PFC) and whole brain gray matter, alongside exploratory vertex-wise analyses. Analyses examined ccf-mtDNA main-effects and ccf-mtDNA-by-diagnosis interaction effects controlling for age, sex, and intracranial volume. Results: There was no significant difference in ccf-mtDNA levels between BD and CG. In ROI analyses, higher ccf-mtDNA was associated with higher PFC surface area (SA) (β = 0.32 p < 0.001) and PFC volume (β = 0.32 p = 0.002) in the overall sample. In stratified analyses, higher ccf-mtDNA was associated with higher PFC SA within both subgroups (BD: β = 0.39 p = 0.02; CG: β = 0.24 p = 0.045). Higher ccf-mtDNA was associated with higher PFC volume within the BD group (β = 0.39 p = 0.046). In vertex-wise analyses, higher ccf-mtDNA was associated with higher SA and volume in frontal clusters within the overall sample and within the BD group. There were significant ccf-mtDNA-by-diagnosis interactions in three frontal and parietal clusters, whereby higher ccf-mtDNA was associated with higher neurostructural metrics in the BD group but lower neurostructural metrics in CG. Conclusions: Contrasting our hypothesis, higher ccf-mtDNA was consistently associated with higher, rather than lower, regional neuralstructural metrics among youth with BD. While this finding may reflect a compensatory mechanism, future repeated-measures prospective studies evaluating the inter-relationship among ccf-mtDNA, mood, and brain structure across developmental epochs and illness stages are warranted. [ABSTRACT FROM AUTHOR]

Introduction: Detection of adverse reactions to drugs and biologic agents is an important component of regulatory approval and post-market safety evaluation. Real-world data, including insurance claims and electronic health records data, are increasingly used for the evaluation of potential safety outcomes; however, there are different types of data elements available within these data resources, impacting the development and performance of computable phenotypes for the identification of adverse events (AEs) associated with a given therapy. Objective: To evaluate the utility of different types of data elements to the performance of computable phenotypes for AEs. Methods: We used intravenous immunoglobulin (IVIG) as a model therapeutic agent and conducted a single-center, retrospective study of 3897 individuals who had at least one IVIG administration between 1 January 2014 and 31 December 2019. We identified the potential occurrence of four different AEs, including two proximal AEs (anaphylaxis and heart rate alterations) and two distal AEs (thrombosis and hemolysis). We considered three different computable phenotypes: (1) an International Classification of Disease (ICD)-based phenotype; (2) a phenotype-based on EHR-derived contextual information based on structured data elements, including laboratory values, medication administrations, or vital signs; and (3) a compound phenotype that required both an ICD code for the AE in combination with additional EHR-derived structured data elements. We evaluated the performance of each of these computable phenotypes compared with chart review-based identification of AEs, assessing the positive predictive value (PPV), specificity, and estimated sensitivity of each computable phenotype method. Results: Compound computable phenotypes had a high positive predictive value for acute AEs such as anaphylaxis and bradycardia or tachycardia; however, few patients had both ICD codes and the relevant contextual data, which decreased the sensitivity of these computable phenotypes. In contrast, computable phenotypes for distal AEs (i.e., thrombotic events or hemolysis) frequently had ICD codes for these conditions in the absence of an AE due to a prior history of such events, suggesting that patient medical history of AEs negatively impacted the PPV of computable phenotypes based on ICD codes. Conclusions: These data provide evidence for the utility of different structured data elements in computable phenotypes for AEs. Such computable phenotypes can be used across different data sources for the detection of infusion-related adverse events. [ABSTRACT FROM AUTHOR]

Background: Evidence-based psychotherapies available to treat patients with bipolar disorders (BD) are limited. Dialectical behavior therapy (DBT) may target several common symptoms of BD. We conducted a systematic review on the efficacy of DBT for mood symptoms in patients with BD. The systematic search used key words related to DBT and BD in Medline, Embase, PsycInfo, CINAHL, and Cochrane Library databases from 1980 to April 1st, 2022. We included studies that enrolled patients with a BD I or II diagnosis (DSM or ICD), age 12 and older who received a DBT-based intervention. Studies reviewed were clinical trials including observational studies that reported at least one outcome related to BD mood symptoms or severity. We did not exclude based upon psychiatric or physical co-morbidity. Results: We screened 848 abstracts and reviewed 28 full texts; 10 publications with 11 studies met our pre-determined eligibility criteria. All but one were feasibility pilot studies and most included participants in all mood states except for mania. The studies provided preliminary evidence suggesting these interventions may be effective for improving several core symptoms of BD. Overall, all the studies consistently supported that DBT-based interventions are feasible and acceptable for patients with BD. Conclusion: DBT may be an effective treatment for BD; however, the confidence in this conclusion is limited by the small sample sizes, heterogeneity, and high risk of bias in all published trials. Larger well-designed RCTs are now required to establish the effectiveness of DBT in BD. [ABSTRACT FROM AUTHOR]

There is a lack of data on resources used and food produced at urban farms. This hampers attempts to quantify the environmental impacts of urban agriculture or craft policies for sustainable food production in cities. To address this gap, we used a citizen science approach to collect data from 72 urban agriculture sites, representing three types of spaces (urban farms, collective gardens, individual gardens), in five countries (France, Germany, Poland, United Kingdom, and United States). We answered three key questions about urban agriculture with this unprecedented dataset: (1) What are its land, water, nutrient, and energy demands? (2) How productive is it relative to conventional agriculture and across types of farms? and (3) What are its contributions to local biodiversity? We found that participant farms used dozens of inputs, most of which were organic (e.g., manure for fertilizers). Farms required on average 71.6 L of irrigation water, 5.5 L of compost, and 0.53 m2 of land per kilogram of harvested food. Irrigation was lower in individual gardens and higher in sites using drip irrigation. While extremely variable, yields at well-managed urban farms can exceed those of conventional counterparts. Although farm type did not predict yield, our cluster analysis demonstrated that individually managed leisure gardens had lower yields than other farms and gardens. Farms in our sample contributed significantly to local biodiversity, with an average of 20 different crops per farm not including ornamental plants. Aside from clarifying important trends in resource use at urban farms using a robust and open dataset, this study also raises numerous questions about how crop selection and growing practices influence the environmental impacts of growing food in cities. We conclude with a research agenda to tackle these and other pressing questions on resource use at urban farms. [ABSTRACT FROM AUTHOR]

Background: CACNA1C rs1006737 A allele, identified as a genetic risk variant for bipolar disorder (BD), is associated with anomalous functional connectivity in adults with and without BD. Studies have yet to investigate the association of CACNA1C rs1006737 with resting-state functional connectivity (rsFC) in youth BD. Methods: Participants included 139 youth with BD-I, -II, or -not otherwise specified, ages 13–20 years, including 27 BD A-carriers, 41 BD non-carriers, 32 healthy controls (HC) A-carriers, and 39 HC non-carriers. Anterior cingulate cortex (ACC), amygdala, and orbitofrontal cortex (OFC) were examined as regions-of-interest in seed-to-voxel analyses. General linear models included main effects of diagnosis and rs1006737, and an interaction term, controlling for age, sex, and race. Results: We observed a main effect of BD diagnosis on rsFC between the right amygdala and the right occipital pole (p = 0.02), and a main effect of rs1006737 genotypes on rsFC between the right OFC and bilateral occipital cortex (p < 0.001). Two significant BD diagnosis-by-CACNA1C rs1006737 interactions were also identified. The A allele was associated with positive rsFC between the right ACC and right amygdala in BD but negative rsFC in HC (p = 0.01), and negative rsFC between the left OFC and left putamen in BD but positive rsFC in HC (p = 0.01). Conclusion: This study found that the rs1006737 A allele, identified as a genetic risk variant for BD in adults, was differentially associated with rsFC in youth with BD in regions relevant to emotion, executive function, and reward. Future task-based approaches are warranted to better understand brain connectivity in relation to CACNA1C in BD. [ABSTRACT FROM AUTHOR]

There is high risk of suicidality in bipolar disorder (BD), particularly in early onset cases. The literature regarding correlates and putative predictors of suicide attempts (SA), non-suicidal self-injury (NSSI) and suicidal ideation (SI) among youth with BD remains sparse. Participants included 197 adolescents with BD, divided into 4 groups: SA (with or without NSSI), NSSI (with or without SI), SI only, and comparison group (CG; no SA/NSSI/SI). Diagnoses, treatment, and suicidality measures were determined via semi-structured interviews, conducted between 2009 and 2017. Univariate analyses were followed by multinomial regression. Overall, 73.6% of participants had history of SA, NSSI, and/or SI. In comparison to CG, SA and NSSI were each associated with BD-II/-NOS (odds ratio [OR] = 15.99, p = 0.002; OR = 16.76, p = 0.003), female sex (OR = 6.89, p = 0.006; OR = 3.76, p = 0.02), and emotion dysregulation (OR = 1.10, p < 0.001; OR = 1.07, p = 0.004). NSSI and SI were each associated with most severe lifetime depression (OR = 1.10, p = 0.01; OR = 1.10, p = 0.01). SA and SI were associated with psychiatric hospitalization (OR = 19.45, p = 0.001; OR = 6.09, p = 0.03). SA was associated with poorer global functioning at most severe episode (OR = 0.88, p = 0.008). NSSI was associated with not living with both natural parents (OR = 0.22, p = 0.009). Study limitations include cross-sectional and retrospective design, stringent cut-offs for SA and NSSI, and recruitment from a tertiary clinical setting. Three quarters of adolescents with BD have had suicidality and/or self-injury. SA and NSSI were most similar to one another, and most different from CG, supporting the broader construct of self-harm. Future research should address the gap in knowledge regarding how sex differences and neurobiology are associated with the observed clinical differences. [ABSTRACT FROM AUTHOR]

There is tremendous interest in understanding how neighborhoods impact health by linking extant social and environmental drivers of health (SDOH) data with electronic health record (EHR) data. Studies quantifying such associations often use static neighborhood measures. Little research examines the impact of gentrification—a measure of neighborhood change—on the health of long-term neighborhood residents using EHR data, which may have a more generalizable population than traditional approaches. We quantified associations between gentrification and health and healthcare utilization by linking longitudinal socioeconomic data from the American Community Survey with EHR data across two health systems accessed by long-term residents of Durham County, NC, from 2007 to 2017. Census block group-level neighborhoods were eligible to be gentrified if they had low socioeconomic status relative to the county average. Gentrification was defined using socioeconomic data from 2006 to 2010 and 2011–2015, with the Steinmetz-Wood definition. Multivariable logistic and Poisson regression models estimated associations between gentrification and development of health indicators (cardiovascular disease, hypertension, diabetes, obesity, asthma, depression) or healthcare encounters (emergency department [ED], inpatient, or outpatient). Sensitivity analyses examined two alternative gentrification measures. Of the 99 block groups within the city of Durham, 28 were eligible (N = 10,807; median age = 42; 83% Black; 55% female) and 5 gentrified. Individuals in gentrifying neighborhoods had lower odds of obesity (odds ratio [OR] = 0.89; 95% confidence interval [CI]: 0.81–0.99), higher odds of an ED encounter (OR = 1.10; 95% CI: 1.01–1.20), and lower risk for outpatient encounters (incidence rate ratio = 0.93; 95% CI: 0.87–1.00) compared with non-gentrifying neighborhoods. The association between gentrification and health and healthcare utilization was sensitive to gentrification definition. [ABSTRACT FROM AUTHOR]

To analyze species count data when detection is imperfect, ecologists need models to estimate relative abundance in the presence of unknown sources of heterogeneity. Two candidate models are generalized linear mixed models (GLMMs) and hierarchical N-mixture models. GLMMs are computationally robust but do not explicitly separate detection from abundance patterns. N-mixture models separately estimate detection and abundance via a latent state but are sensitive to violations in assumptions and subject to practical estimation issues. When one can assume that detection is not systematically confounded with ecological patterns of interest, these two models can be viewed as sharing a heuristic framework for relative abundance estimation. Model selection can then determine which predicts observed counts best, for example by AIC. We compared four N-mixture model variants and two GLMM variants for predicting bird counts in local subsets of a citizen science dataset, eBird, based on model selection and goodness-of-fit measures. We found that both GLMMs and N-mixture models—especially N-mixtures with beta-binomial detection submodels—were supported in a moderate number of datasets, suggesting that both tools are useful and that relative fit is context-dependent. We provide faster software implementations of N-mixture likelihood calculations and a reparameterization to interpret unstable estimates for N-mixture models. [ABSTRACT FROM AUTHOR]

Background: Early hypotension following moderate to severe traumatic brain injury (TBI) is associated with increased mortality and poor long-term outcomes. Current guidelines suggest the use of intravenous vasopressors to support blood pressure following TBI; however, guidelines do not specify vasopressor type, resulting in variation in clinical practice. Minimal data are available to guide clinicians on optimal early vasopressor choice to support blood pressure following TBI. Therefore, we conducted a multicenter study to examine initial vasopressor choice for the support of blood pressure following TBI and its association with clinical and functional outcomes after injury. Methods: We conducted a retrospective cohort study of patients enrolled in the transforming research and clinical knowledge in traumatic brain injury (TRACK-TBI) study, an 18-center prospective cohort study of patients with TBI evaluated in participating level I trauma centers. We examined adults with moderate to severe TBI (defined as Glasgow Coma Scale score < 13) who were admitted to the intensive care unit and received an intravenous vasopressor within 48 h of admission. The primary exposure was initial vasopressor choice (phenylephrine versus norepinephrine), and the primary outcome was 6-month Glasgow Outcomes Scale Extended (GOSE), with the following secondary outcomes: length of hospital stay, length of intensive care unit stay, in-hospital mortality, new requirement for dialysis, and 6-month Disability Rating Scale. Regression analysis was used to assess differences in outcomes between patients exposed to norepinephrine versus phenylephrine, with propensity weighting to address selection bias due to the nonrandom allocation of the treatment groups and patient dropout. Results: The final study sample included 156 patients, of whom 79 (51%) received norepinephrine, 69 (44%) received phenylephrine, and 8 (5%) received an alternate drug as their initial vasopressor. 121 (77%) of patients were men, with a mean age of 43.1 years. Of patients receiving norepinephrine as their initial vasopressor, 32% had a favorable outcome (GOSE 5–8), whereas 40% of patients receiving phenylephrine as their initial vasopressor had a favorable outcome. Compared with phenylephrine, exposure to norepinephrine was not significantly associated with improved 6-month GOSE (weighted odds ratio 1.40, 95% confidence interval 0.66–2.96, p = 0.37) or any secondary outcome. Conclusions: The majority of patients with moderate to severe TBI received either phenylephrine or norepinephrine as first-line agents for blood pressure support following brain injury. Initial choice of norepinephrine, compared with phenylephrine, was not associated with improved clinical or functional outcomes. [ABSTRACT FROM AUTHOR]

As wearable technologies are being increasingly used for clinical research and healthcare, it is critical to understand their accuracy and determine how measurement errors may affect research conclusions and impact healthcare decision-making. Accuracy of wearable technologies has been a hotly debated topic in both the research and popular science literature. Currently, wearable technology companies are responsible for assessing and reporting the accuracy of their products, but little information about the evaluation method is made publicly available. Heart rate measurements from wearables are derived from photoplethysmography (PPG), an optical method for measuring changes in blood volume under the skin. Potential inaccuracies in PPG stem from three major areas, includes (1) diverse skin types, (2) motion artifacts, and (3) signal crossover. To date, no study has systematically explored the accuracy of wearables across the full range of skin tones. Here, we explored heart rate and PPG data from consumer- and research-grade wearables under multiple circumstances to test whether and to what extent these inaccuracies exist. We saw no statistically significant difference in accuracy across skin tones, but we saw significant differences between devices, and between activity types, notably, that absolute error during activity was, on average, 30% higher than during rest. Our conclusions indicate that different wearables are all reasonably accurate at resting and prolonged elevated heart rate, but that differences exist between devices in responding to changes in activity. This has implications for researchers, clinicians, and consumers in drawing study conclusions, combining study results, and making health-related decisions using these devices. [ABSTRACT FROM AUTHOR]

Objective: To characterize self-poisoning suicide deaths in BD compared to other suicide decedents. Methods: Extracted coroner data from all suicide deaths ( n = 3319) in Toronto, Canada from 1998 to 2012. Analyses of demographics, clinical history, recent stressors, and suicide details were conducted in 5 subgroups of suicide decedents: BD self-poisoning, BD other methods, non-BD self-poisoning, non-BD other methods, and unipolar depression self-poisoning. Toxicology results for lethal and present substances were also compared between BD and non-BD self-poisoning subgroups as well as between BD and unipolar depression self-poisoning subgroups. Results: Among BD suicide decedents, self-poisoning was significantly associated with female sex, past suicide attempts, and comorbid substance abuse. In both the BD and non-BD self-poisoning groups, opioids were the most common class of lethal medication. For both groups, benzodiazepines and antidepressants were the most common medications present at time of death, and in 23% of the BD group, an antidepressant was present without a mood stabilizer or antipsychotic. Only 31% of the BD group had any mood stabilizer present, with carbamazepine being most common. No antidepressant, mood stabilizer, or antipsychotic was present in 15.5% of the BD group. Relative to unipolar depression self-poisoning group, the BD self-poisoning group evidenced higher proportion of previous suicide attempt(s) and psychiatry/ER visits in the previous week. Conclusion: People with BD who die by suicide via self-poisoning comprise a distinct but understudied group. The predominant absence of guideline-concordant pharmacologic care comprises a crucial target for future policy and knowledge translation efforts. [ABSTRACT FROM AUTHOR]

Background: Executive dysfunction is common and impairing in youth bipolar disorder (BD), and oxidative stress (OS) and brain-derived neurotrophic factor (BDNF) have been implicated in executive deficits of adult BD. This study aimed to determine the association between OS and executive dysfunction in BD adolescents and the influence of BDNF on this association. Methods: Serum levels of lipid hydroperoxides (LPH) and 4-hydroxy-2-nonenal (4-HNE) and BDNF levels were measured in 29 BD and 25 control adolescents. The intra-extra-dimensional (IED) set-shifting task assessed executive function. Lower IED scores indicated better performance. High and low BDNF subgroups were defined by median split. Results: IED Z-scores were impaired in the BD group compared to controls, whereas biomarker levels were not significantly different between groups. LPH-BDNF correlations were significantly different between BD and controls ( Z = 2.046, p = 0.041). In high BDNF BD subjects, LPH was significantly positively correlated with IED completed stage trials ( ρ = 0.755, p = 0.001) and pre-extra-dimensional shift errors ( ρ = 0.588, p = 0.017). Correlations were opposite in controls. In a linear model, LPH, BDNF, and the LPH-BDNF interaction each significantly explained variance of IED total trials (adjusted) (model r = 0.187, F = 2.811, p = 0.035). Conclusions: There is a negative association between LPH and executive function in BD adolescents, which may be modulated by BDNF. LPH and BDNF may be useful biomarkers of executive function in BD. These findings highlight the importance of examining multiple peripheral biomarkers in relation to cognitive functions in BD adolescents. Future studies should explore these factors in longitudinal designs to determine the directionality of observed associations. [ABSTRACT FROM AUTHOR]

Greater understanding of cognitive function in children and adolescents with bipolar disorder (BD) is of critical importance to improve our ability to design targeted treatments to help with real-world impairment, including academic performance. We sought to evaluate cognitive performance among children with either BD type I, II, or 'not otherwise specified' (NOS) participating in multi-site Course and Outcome of Bipolar Youth study compared to typically developing controls (TDC) without psychopathology. In particular, we sought to test the hypothesis that BD-I and BD-II youths with full threshold episodes of mania or hypomania would have cognitive deficits, including in reversal learning, vs. those BD-NOS participants with sub-threshold episodes and TDCs. N = 175 participants (BD-I = 81, BD-II = 11, BD-NOS = 28, TDC = 55) completed Cambridge Neuropsychological Automated Testing Battery (CANTAB) tasks. A priori analyses of the simple reversal stage of the CANTAB intra-/extra-dimensional shift task showed that aggregated BD-I/II participants required significantly more trials to complete the task than either BD-NOS participants with sub-syndromal manic/hypomanic symptoms or than TDCs. BD participants across sub-types had impairments in sustained attention and information processing for emotionally valenced words. Our results align with prior findings showing that BD-I/II youths with distinct episodes have specific alterations in reversal learning. More broadly, our study suggests that further work is necessary to see the interaction between neurocognitive performance and longitudinal illness course. Additional work is required to identify the neural underpinnings of these differences as targets for potential novel treatments, such as cognitive remediation. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is exceedingly prevalent among adults with bipolar disorder (BD), implicating BD adolescents as a high-risk group for CVD. Non-invasive ultrasound measures of vascular structure (via carotid intima media thickness [cIMT]) and function (via flow-mediated dilation [FMD]) predict future CVD, and are associated with traditional CVD risk factors among adolescents without mood disorders. This study examined, for the first time, the association of cIMT and FMD with CVD risk factors among adolescents with BD. The presence of multiple potential confounds among adolescents with BD, including various medications and mood states, informs the need to demonstrate whether cIMT and FMD are associated with CVD risk factors in this population specifically. Participants were 30 adolescents, 13-19 years old, with BD, without CVD. High-resolution ultrasonography was used to evaluate vascular structure (cIMT) and function (FMD). Analyses examined associations of cIMT and FMD with traditional CVD risk factors. cIMT was significantly positively associated with systolic blood pressure and waist circumference. FMD was significantly negatively associated with waist circumference, body mass index, triglycerides, and glucose, and positively associated with high-density lipoprotein. cIMT and FMD are associated with traditional CVD risk factors among adolescents with BD. Irrespective of numerous potential confounds, non-invasive vascular ultrasound approaches may be used as CVD risk proxies among adolescents with BD as they are for other adolescents. [ABSTRACT FROM AUTHOR]

The importance of biomarkers to many branches of medicine is illustrated by their utility in diagnosis and monitoring treatment response and outcome. There is much enthusiasm in the field of mood disorders on the emergence of clinically relevant biomarkers with several potential targets. While there are generally accepted criteria to establish a biomarker, such approaches are premature for our field as we acquire evidence on the most relevant candidates. A number of components of the inflammatory pathway are supported by published data together with an increasing focus on brain-derived neurotrophic factor. These markers may have measurable impacts on endothelial function, which may be particularly amenable to study in clinical samples. The adolescent population is a key focus as identifying biomarkers before the onset of comorbid medical conditions and which may help direct early intervention seem especially promising. A systematic approach to biomarker development in mood disorders is clearly warranted. [ABSTRACT FROM AUTHOR]

Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r2 < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways. [ABSTRACT FROM AUTHOR]

The prevalence and penetrance of BRCA1 and BRCA2 ( BRCA1/2) mutations may differ between Asians and whites. We investigated BRCA1/2 mutations and cancer risk factors in a clinic-based sample. BRCA1/2 mutation carriers were enrolled from cancer genetics clinics in Hong Kong and California according to standardized entry criteria. We compared BRCA mutation position, cancer history, hormonal and reproductive exposures. We analyzed DNA samples for single-nucleotide polymorphisms reported to modify breast cancer risk. We performed logistic regression to identify independent predictors of breast cancer. Fifty Asian women and forty-nine white American women were enrolled. BRCA1 mutations were more common among whites (67 vs. 42 %, p = 0.02), and BRCA2 mutations among Asians (58 vs. 37 %, p = 0.04). More Asians had breast cancer (76 vs. 53 %, p = 0.03); more whites had relatives with breast cancer (86 vs. 50 %, p = 0.0003). More whites than Asians had breastfed (71 vs. 42 %, p = 0.005), had high BMI (median 24.3 vs. 21.2, p = 0.04), consumed alcohol (2 drinks/week vs. 0, p < 0.001), and had oophorectomy (61 vs. 34 %, p = 0.01). Asians had a higher frequency of risk-associated alleles in MAP3K1 (88 vs. 59 %, p = 0.005) and TOX3/TNRC9 (88 vs. 55 %, p = 0.0002). On logistic regression, MAP3K1 was associated with increased breast cancer risk for BRCA2, but not BRCA1 mutation carriers; breast density was associated with increased risk among Asians but not whites. We found significant differences in breast cancer risk factors between Asian and white BRCA1/2 mutation carriers. Further investigation of racial differences in BRCA1/2 mutation epidemiology could inform targeted cancer risk-reduction strategies. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system with a strong genetic component. Several lines of evidence support a strong role for genetic factors influencing both disease susceptibility and clinical outcome in MS. Identification of genetic variants that distinguish particular disease subgroups and/or predict a severe clinical outcome is critical to further our understanding of disease mechanisms and guide development of effective therapeutic approaches. We studied 1470 MS cases and performed a genome-wide association study of more than 2.5 million single-nucleotide polymorphisms to identify loci influencing disease severity, measured using the MS severity score (MSSS), a measure of clinical disability. Of note, no single result achieved genome-wide significance. Furthermore, variants within previously confirmed MS susceptibility loci do not appear to influence severity. Although bioinformatic analyses highlight certain pathways that are over-represented in our results, we conclude that the genetic architecture of disease severity is likely polygenic and comprised of modest effects, similar to what has been described for MS susceptibility, to date. However, a role for major effects of rare variants cannot be excluded. Importantly, our results also show the MSSS, when considered as a binary or continuous phenotype variable is by comparison a stable outcome. [ABSTRACT FROM AUTHOR]

Bipolar disorder is a multidimensional illness typified by fluctuating periods of depression and mania, cognitive dysfunction, abnormal circadian rhythms, and multiple comorbid psychiatric and general medical conditions. Indefinite pharmacological treatment is often required, yet the modest effects of available treatments and frequent difficulties with tolerability and adherence present complex challenges to patients. Long-acting injectable medications offer a therapeutic alternative to oral mood stabilizers and may help facilitate long-term treatment adherence. This article will provide a succinct review of the latest data on the use of long-acting injectable risperidone (LAR) during the maintenance-phase treatment of bipolar disorder. The specific role of LAR in comparison to other atypical antipsychotics, and the limitations of available studies will be discussed from the perspectives of efficacy, tolerability, and sequential positioning in treatment guidelines. [ABSTRACT FROM AUTHOR]

The metabolic syndrome and its components are associated with depressive symptomatology. This article discusses the rate of co-occurrence and the points of pathophysiologic commonality between the metabolic syndrome and major depressive disorder. [ABSTRACT FROM AUTHOR]

There has been an exponential increase in recent years of literature pertaining to the treatment of individuals with alcohol use disorders and co-morbid psychiatric disorders. Patients with mood and anxiety disorders in particular have a very high prevalence of alcoholism. Alcoholism confers significant morbid risks to patients with psychiatric disorders, and vice versa, including markedly increased risk of suicide. Only recently have studies examined the impact of various psychiatric medications on alcohol use among patients with these disorders. Evidence supporting the benefits of antidepressants for co-morbid alcoholism and depression continues to mount. Although these studies have demonstrated benefits in terms of quantitative decreases in the volume and frequency of consumption, the benefits in terms of remission from alcoholism have yet to be shown conclusively.The first randomised, controlled trial involving subjects with co-morbid alcoholism and bipolar disorder was recently conducted, yielding promising results for valproate in this population. The literature regarding co-morbid alcoholism and anxiety disorders has also seen recent progress, particularly in the study of post-traumatic stress disorder (PTSD). A placebo-controlled study of sertraline suggests some benefit in terms of alcohol use among individuals with early-onset PTSD and less severe alcohol dependence. Atypical antipsychotics such as olanzapine and quetipaine have been examined in several open studies of subjects with alcoholism co-morbid with a variety of psychiatric conditions including bipolar disorder, PTSD and schizophrenia. This paper selectively reviews the evidence that is currently available for the pharmacological management of alcoholism among persons with co-morbid psychiatric illness. Effectiveness, safety and tolerability are considered, and directions for future study are discussed. [ABSTRACT FROM AUTHOR]

Gender differences in alcohol consumption and depressive symptoms are well known. This study focused on the associations of gender with attributional style, coping style, and negative life events in explaining these differences. The association of gender with each of the predictor and outcome variables was examined. One hundred eight (51 men, 57 women) undergraduate university students, ages 18-21, completed validated measures of depression, alcohol consumption, attributional style, coping style, and negative life events. Participants reported mild-moderate levels of depressive symptoms, similar to comparable samples. In contrast, alcohol consumption was lower than expected. Depressive symptoms were associated with negative events and rumination among both men and women. Pessimism and wine consumption were correlated with depression among women only. Although men consumed more alcohol than did women, a gender difference in depressive symptoms was not found. Potential implications of these findings are discussed. [ABSTRACT FROM AUTHOR]

Data sourcesThe following databases were searched: Cochrane Oral Health Trial Register, Cochrane central register for controlled trials, Medline Ovid and Embase Ovid. The following were searched for ongoing trials: US National Institutes of Health Trials Register and World Health Organization International Clinical Trials Registry Platform. No language, publication year or publication status restrictions were imposed.Study selectionRandomised controlled trials (RCTs) and controlled clinical trials (CCTs) of orthodontic treatment to correct deep bite and retroclined upper front teeth were included. Two independent reviewers scanned and reviewed all papers and abstracts to be included. When necessary, primary authors were contacted, and additional or missing information was obtained. Trials which recruited participants 16 years or less without surgical intervention to correct their class II malocclusion were to be included. Trials that included participants with cleft lip/palate or any other craniofacial syndrome were excluded.Data extraction and synthesisIf data were to be selected, all data would have been complied into a customised data collection form. The following were to be included in the analysis; year of publication, country of origin, setting and source of study funding and details on the type of interventions including appliance type. Additionally, details of the participants including demographic characteristics, criteria for inclusion and exclusion and sample size by study group were to be taken into account. Details of the outcomes reported, including method of assessment, time intervals, details of withdrawals by study group, details of outcomes, including measures and timepoints were also supposed to be compiled for completeness. The risk of bias was planned to be reviewed. Measurements of treatment effect including risk ratios and numbers needed to treat would have been included. A 95% confidence interval and assessment of heterogeneity were to be explored. Data synthesis was planned to follow the Cochrane statistical guidelines using Review Manager Software.ResultsOne thousand three hundred and forty-four records were identified through database searching and one extra article was identified through other sources. Eight hundred and fifty-seven records were isolated after duplicates were removed. All records were rejected. No articles were selected for inclusion. No RCTs or CCTs were found assessing orthodontic treatment without the removal of permanent teeth versus treatment with extraction of permanent teeth versus no treatment at all. Consequently, it is impossible to derive any evidence-based support for clinicians for the treatment of class II division 2 malocclusion in children.ConclusionsThere is no evidence from clinical trials to recommend or discourage any type of orthodontic treatment to correct Class II division 2 malocclusion in children. This situation seems unlikely to change as trials to evaluate the best management of Class II division 2 malocclusion are challenging to design and conduct due to low prevalence, difficulties with recruitment and ethical issues with randomisation. [ABSTRACT FROM AUTHOR]