Food environment index and preterm birth rate in the counties of the United States.

OBJECTIVES: To determine the relationship between Food Environment Index (FEI) and Preterm Birth (PTB) rate at the county level of the United States of America (USA) (primary), while evaluating the interaction of multiple factors within a framework of sociodemographic, maternal health, maternal behavioral, and environmental factors. METHODS: This is a population-based retrospective cohort ecological study from 2015-2018. The study compares the characteristics of the population of the counties of the USA. All counties with complete data on their PTB rate and the independent variables were included in the study. Independent variables with greater than 20% missing data were excluded from the study. Purposive sampling technique was applied. A total of 2983/3142 counties were included in the study. RESULTS: The median PTB rate of all counties was 9.90%. The highest PTB rate (23.3%) was in Tallapoosa County, Alabama and the lowest (3.4%) in San Juan County, Washington State. After adjusting for variables, PTB rate had a significant association with FEI (coefficient of correlation - 0.36, p < 0.01, 95% CI - 0.19 to - 0.04). Increase in the rate of unemployment, African American race, adult smoking, obesity, uninsured rate, sexually transmitted diseases (STD), high school education and air pollution was associated with an increase in PTB rate, while an increase in FEI and alcohol abuse rates was associated with a decrease in PTB rate. CONCLUSIONS: FEI can predict the PTB rate in USA counties after adjusting for sociodemographic, health, behavioral and environmental factors. Future studies are needed to confirm these associations and consider them when making policies to reduce PTBs.

Racial and Ethnic Differences in BRCA1/2 and Multigene Panel Testing Among Young Breast Cancer Patients.

Genetic testing for hereditary breast and ovarian cancer (HBOC) is recommended for breast cancer patients diagnosed at age ≤ 50 years. Our objective was to examine racial/ethnic differences in genetic testing frequency and results among diverse breast cancer patients. A retrospective cohort study among women diagnosed with breast cancer at age ≤ 50 years from January 2007 to December 2017 at Columbia University in New York, NY. Among 1503 diverse young breast cancer patients, nearly half (46.2%) completed HBOC genetic testing. Genetic testing completion was associated with younger age, family history of breast cancer, and earlier stage, but not race/ethnicity or health insurance status. Blacks had the highest frequency of pathogenic/likely pathogenic (P/LP) variants (18.6%), and Hispanics and Asians had the most variants of uncertain significance (VUS), 19.0% and 21.9%, respectively. The percentage of women undergoing genetic testing increased over time from 15.3% in 2007 to a peak of 72.8% in 2015. Over the same time period, there was a significant increase in P/LP and VUS results. Due to uncertainty about the clinical implications of P/LP variants in moderate penetrance genes and VUSs, our findings underscore the need for targeted genetic counseling education, particularly among young minority breast cancer patients.

Gender and racial/ethnic differences in physiologic responses in the Stimulant Reduction Intervention using Dosed Exercise Study.

Exercise may be beneficial for individuals in substance use disorder (SUD) treatment given the higher rates of both medical and psychiatric comorbidity, namely mood and anxiety disorders, compared to the general population. Gender and/or racial/ethnic differences in health benefits and response to prescribed exercise have been reported and may have implications for designing exercise interventions in SUD programs. METHOD: Data are from the National Drug Abuse Treatment Clinical Trials Network (NIDA/CTN) Stimulant Reduction Intervention using Dosed Exercise (STRIDE) trial. Gender differences across racial/ethnic groups in physiological responses and stimulant withdrawal severity across time were analyzed using linear mixed effects models. RESULTS: Males completed significantly more exercise sessions than females and were more adherent to the prescribed exercise dose of 12 Kcal/Kg/Week. Controlling for age, race/ethnicity, treatment group and stimulant withdrawal severity, there was a significant gender by time interaction for body mass index (BMI) (p < 0.001), waist circumference (p < 0.001) and heart rate measured prior to exercise sessions (p < 0.01). For females, body mass index (BMI) and waist circumference increased over time while for males BMI and waist circumference stayed unchanged or slightly decreased with time. Heart rate over time significantly increased for females at a higher rate than in males. Stimulant withdrawal severity was similar in males and females at baseline but males exhibited a significant decrease over time while females did not. Although baseline differences were observed, there were no time by race/ethnicity differences in physiologic responses. DISCUSSION: Gender differences in response to exercise may have implications for developing gender specific exercise interventions in SUD programs.

Prospective, randomized, double-blind assessment of topical bakuchiol and retinol for facial photoageing.

BACKGROUND: Bakuchiol is a phytochemical that has demonstrated cutaneous antiageing effects when applied topically. Early studies have suggested that bakuchiol is a functional analogue of topical retinoids, as both compounds have been shown to induce similar gene expression in the skin and lead to improvement of cutaneous photodamage. No in vivo studies have compared the two compounds for efficacy and side-effects. OBJECTIVES: To compare the clinical efficacy and side-effect profiles of bakuchiol and retinol in improving common signs of cutaneous facial ageing. METHODS: This was a randomized, double-blind, 12-week study in which 44 patients were asked to apply either bakuchiol 0·5% cream twice daily or retinol 0·5% cream daily. A facial photograph and analytical system was used to obtain and analyse high-resolution photographs of patients at 0, 4, 8 and 12 weeks. Patients also completed tolerability assessment questions to review side-effects. During study visits, a board-certified dermatologist, blinded to study group assignments, graded pigmentation and redness. RESULTS: Bakuchiol and retinol both significantly decreased wrinkle surface area and hyperpigmentation, with no statistical difference between the compounds. The retinol users reported more facial skin scaling and stinging. CONCLUSIONS: Our study demonstrates that bakuchiol is comparable with retinol in its ability to improve photoageing and is better tolerated than retinol. Bakuchiol is promising as a more tolerable alternative to retinol.

Definition of treatment-resistant depression - Asia Pacific perspectives.

BACKGROUND: The lack of uniformity in the definition of treatment resistant depression (TRD) within the Asia-Pacific (APAC) region may have implications for patient management. We aimed to characterize the most commonly used TRD definition in selected APAC countries. METHODS: A systematic literature review of TRD definitions in APAC countries was conducted in Medline and Embase (2010-2016) and conference proceedings (2014 and 2016). TRD guidelines (APAC, Europe regional, US, or international) were also searched. An expert-panel explored APAC nuances in TRD definitions to achieve consensus for a regional-level definition. RESULTS: Ten guidelines and 89 studies qualified for study inclusion. Among the studies, variations were observed in definitions regarding: number of antidepressants failed (range: ≥1 to ≥3), classes of antidepressants (same or different; 59% did not specify class), duration of previous treatments (range: 4-12 weeks), dosage adequacy, and consideration of adherence (yes/no; 88% of studies did not consider adherence). No TRD-specific guidelines were identified. The emerging consensus from the literature review and panel discussion was that TRD is most commonly defined as failure to ≥2 antidepressant therapies given at adequate doses, for 6-8 weeks during a major depressive episode. LIMITATIONS: Few studies provided definitions of TRD used in daily clinical practice, and a limited number of countries were represented in the included studies and expert panel. CONCLUSION: Attaining consensus on TRD definition may promote accurate, and possibly early detection of patients with TRD to enable appropriate intervention that may impact patient outcomes and quality of life.

Synthesis, characterization and application of green seaweed mediated silver nanoparticles (AgNPs) as antibacterial agents for water disinfection.

A simple and eco-friendly method for the synthesis of hybrid bead silver nanoparticles (AgNPs) employing the aqueous extract derived from natural and renewable source namely tropical benthic green seaweed Ulva flexuosa was developed. This route involves the reduction of Ag+ ions anchored onto macro porous methacrylic acid copolymer beads to AgNPs for employing them as antibacterial agents for in vitro water disinfection. The seaweed extract itself acts as a reducing and stabilizing agent and requires no additional surfactant or capping agent for forming the AgNPs. The nanoparticles were analyzed using high-resolution transmission electron microscopy, UV-Vis spectroscopy, Fourier transform infrared spectroscopy, scanning electron microscopy, energy dispersive X-ray analysis and inductively coupled plasma optical emission spectroscopy. The study elucidates that such biologically synthesized AgNPs exhibit potential antibacterial activity against two Gram positive (Bacillus subtilis, Staphylococcus aureus) and two Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacterial strains tested. The bacterial count in treated water was reduced to zero for all the strains. Atomic force microscopy was performed to confirm the pre- and post-state of the bacteria with reference to their treatment with AgNPs. Attributes like facile environment-friendly procedure, stability and high antibacterial potency propel the consideration of these AgNPs as promising antibacterial entities.

The Spectrum of Focal Segmental Glomerulosclerosis from Eastern India: Is It Different?

Focal segmental glomerulosclerosis (FSGS) is a disease that is defined entirely by its histopathological appearance. The recent Columbian classification has grouped this disease into various types based on the light microscopic description. There is a paucity of data describing the distribution of its various subtypes from the Indian subcontinent. This study was undertaken with the aim to throw light on the epidemiology and clinical features of primary FSGS in Eastern India. This retrospective study includes our cohort of biopsy-proven FSGS who presented to us from June 2009 to July 2011 and the analysis of their presenting clinical and histopathological features from our center in East India. Out of 347 patients diagnosed with FSGS in this period, 224 patients were included in the study. A total of 167 cases were of not otherwise specified (NOS) variant (74.5%), 30 tip variant (13.39%), 14 perihilar (6.25%), 8 cellular (3.57%), and 5 to the collapsing variant (2.23%). The maximum proteinuria at presentation was seen with the tip variant (7.98 ± 6.6 g/24 h), and the renal functions were most deranged at presentation with the collapsing variant. These findings were different from those described in other populations including higher prevalence of the tip and the perihilar variant, significant difference in the degree of hypertension, proteinuria, and renal dysfunction among the different variants. The Columbian classification has helped to stratify the outcomes of this glomerular disease with respect to its clinical presentation as well as histopathological features. However, the characteristics of the various variants do show a distinctive pattern in various populations based on ethnicities.

Impact of CYP2D6 polymorphisms on endoxifen concentrations and breast cancer outcomes.

We investigated the impact of germline CYP2D6 genotyping done using the non-tumor specimen on endoxifen concentrations and/or clinical outcomes in breast cancer (BC) patients treated with tamoxifen in published studies. We evaluated published data from 13 001 patients in 29 studies. Mean±s.d. endoxifen concentrations were significantly lower in poor metabolizers (PM) versus extensive metabolizers (EM) (8.8±7.2 versus 22.3±11.8 ng ml-1; P<0.05). The PM status did not influence clinical outcomes in majority of the studies. However, only one study followed the Gaedigk activity scoring for phenotypic assignments, which predicted recurrence-free survival in CYP2D6 poor metabolizers. In two independent studies with 1676 patients, low endoxifen concentrations predicted poor BC-free survival. From our review of published data we found that standardization of CYP2D6 genotype-phenotype classification is needed in order to ensure effective evaluation of associations between CYP2D6 polymorphisms and endoxifen concentrations and BC outcomes. Universal implementation of this standardization classification system should be a priority among researchers and laboratories. Furthermore, additional clinical research is warranted to determine whether patients with CYP2D6 PM phenotypes or low endoxifen levels will have better clinical outcomes with increased tamoxifen dosing compared to standard dosing.

The Epidemiology, Clinical Features, and Outcome of Infection-related Glomerulonephritis from East India: A Single Center Experience.

Infection-related glomerulonephritis (IRGN) is an example of immunological renal injury due to non-renal infections. With the changing face of IRGN over the years, renal biopsy definitely has an important role to play in differentiating this disease from the other masquerades and helps in prognosticating the long-term outcomes. This prospective study includes biopsy-proven IRGN cases who presented to us from July 2010 to July 2013 from a single center in East India. Of the 168 patients suspected and screened, 137 patients were proved to have IRGN. About 11.67% cases were proven to be immunoglobulin A-IRGN variant. The mean age of presentation was 22.7 ± 15.8 years with a slight male preponderance. A nephrotic range of proteinuria was seen in 13.8% cases and 17.5% patient required renal replacement therapy at presentation. Around 8.75% patients had persistent proteinuria despite normal renal function beyond 6 months of follow-up and 8.09% patients progressed to chronic kidney disease. It may no longer be classified as a glomerular disease with the definite favorable outcome as an important number of patients may progress to chronicity following this disease. Renal biopsy plays an important role in the assessment of prognosis of IRGN and detection of the presence of other underlying glomerulonephritis and should be considered early, especially in patients with atypical presentation.

A review of the safety of cosmetic procedures during pregnancy and lactation.

The safety of cosmetic procedures in patients who are pregnant and/or lactating is a complex clinical question surrounded by uncertainty. Our objective is to consolidate data on the safety of commonly requested cosmetic procedures during pregnancy and lactation after a systematic review of the current literature to guide evidence-based care in the future. A systematic search of the PubMed database was conducted for articles on cosmetic procedures during pregnancy and lactation. Due to a lack of controlled trials, case reports and series were considered. Minor procedures such as shave, punch, snipping, and electrocautery are considered safe. With respect to chemical peels, glycolic and lactic acid peels are deemed safe; however, trichloracetic and salicylic acid peels should be avoided or used with caution. Although safety data on botulinum toxin A is insufficient, the procedure may be safe because systemic absorption and placental transfer are negligible. Sclerotherapy can be safe during pregnancy but must be avoided during the first trimester and after week 36 of the pregnancy. Laser and light therapies have been considered generally safe for patients with granulomatous conditions and condylomata. Epilation should be limited to waxing, shaving, and topical treatments instead of permanent procedures. In patients who are lactating, most therapies discussed above are safe but fat transfer, sclerotherapy, and tumescent liposuction are not recommended. Better evidence is needed to make concrete recommendations on the safety of cosmetic therapy during pregnancy and lactation but preliminary evidence suggests excellent safety profiles for many commonly requested cosmetic procedures.

A Review of hormone-based therapies to treat adult acne vulgaris in women.

Hormone-based therapies including combined oral contraceptive medications and spironolactone are considered effective therapies to treat adult acne in women. Our objective is to provide a concise and comprehensive overview of the types of hormonal therapy that are available to treat acne and comment on their efficacy and safety profiles for clinical practice. A systematic search using the PubMed Database was conducted to yield 36 relevant studies for inclusion in the review and several conclusions were drawn from the literature. Treatment with oral contraceptive pills leads to significant reductions in lesion counts across all lesion types compared with placebo. There were no consistent differences in efficacy between the different combined oral contraceptive formulations. In terms of risk, oral contraceptive pill users had three-times increased odds of venous thromboembolism versus non-users according to a recent meta-analysis (95% confidence interval 2.46-2.59). Data on oral contraceptive pill use and breast cancer risk are conflicting but individual patient risk factors and histories should be discussed and considered when prescribing these medications. However, use of these medications does confer measurable protection from endometrial and ovarian cancer. Spironolactone was also shown to be an effective alternative treatment with good tolerability. Combined oral contraceptive medications and spironolactone as adjuvant and monotherapies are safe and effective to treat women with adult acne. However, appropriate clinical examinations, screening, and individual risk assessments particularly for venous thromboembolism risk must be conducted prior to initiating therapy.

A review of laser and light therapy in melasma.

Melasma is a dysregulation of the homeostatic mechanisms that control skin pigmentation and excess pigment is produced. Traditional treatment approaches with topical medications and chemical peels are commonly used but due to the refractory and recurrent nature of melasma, patients often seek alternative treatment strategies such as laser and light therapy. Several types of laser and light therapy have been studied in the treatment of melasma. Intense pulsed light, low fluence Q-switched lasers, and non-ablative fractionated lasers are the most common lasers and light treatments that are currently performed. They all appear effective but there is a high level of recurrence with time and some techniques are associated with an increased risk for postinflammatory hyper- or hypopigmentation. The number and frequency of treatments varies by device type but overall, Q-switched lasers require the greatest number of treatment applications to see a benefit. Vascular-specific lasers do not appear to be effective for the treatment of melasma. Ablative fractionated lasers should be used with caution because they have a very high risk for postinflammatory hypo- and hyperpigmentation. The use of nonablative fractionated laser treatments compared with other laser and light options may result in slightly longer remission intervals. Picosecond lasers, fractional radiofrequency, and laser-assisted drug delivery are promising future approaches to treat melasma. The goal of this review is to summarize the efficacy and safety of the most commonly used laser and light therapies to treat melasma, briefly present future laser-based treatment options for patients with melasma, and provide recommendations for treatment on the basis of the reviewed information.

Racial and ethnic differences in treatment outcomes among adults with stimulant use disorders after a dosed exercise intervention.

The current study examined differences in substance abuse treatment outcomes among racial and ethnic groups enrolled in the Stimulant Reduction Intervention using Dosed Exercise (STRIDE) trial, a multisite randomized clinical trial implemented through the National Institute on Drug Abuse's (NIDA's) Clinical Trials Network (CTN). STRIDE aimed to test vigorous exercise as a novel approach to the treatment of stimulant abuse compared to a health education intervention. A hurdle model with a complier average causal effects (CACE) adjustment was used to provide an unbiased estimate of the exercise effect had all participants been adherent to exercise. Among 214 exercise-adherent participants, we found significantly lower probability of use for Blacks (z = -2.45, p = .014) and significantly lower number of days of use for Whites compared to Hispanics (z = -54.87, p = <.001) and for Whites compared to Blacks (z = -28.54, p = <.001), which suggests that vigorous, regular exercise might improve treatment outcomes given adequate levels of adherence.

Effects of depression, metabolic syndrome, and cardiorespiratory fitness on mortality: results from the Cooper Center Longitudinal Study.

BACKGROUND: Depression and metabolic syndrome (MetS) are frequently comorbid disorders that are independently associated with premature mortality. Conversely, cardiorespiratory fitness (CRF) is associated with reduced mortality risk. These factors may interact to impact mortality; however, their effects have not been assessed concurrently. This analysis assessed the mortality risk of comorbid depression/MetS and the effect of CRF on mortality in those with depression/MetS. METHODS: Prospective study of 47 702 adults in the Cooper Center Longitudinal Study. Mortality status was attained from the National Death Index. History of depression was determined by patient response (yes or no) to a standardized medical history questionnaire. MetS was categorized using the American Heart Association/National Heart, Lung, and Blood Institute criteria. CRF was estimated from the final speed/grade of a treadmill graded exercise test. RESULTS: 13.9% reported a history of depression, 21.4% met criteria for MetS, and 3.0% met criteria for both MetS and history of depression. History of depression (HR = 1.24, p = 0.003) and MetS (HR = 1.28, p < 0.001) were independently associated with an increased mortality risk, with the greatest mortality risk among individuals with both a history of depression and MetS (HR = 1.59, p < 0.001). Higher CRF was associated with a significantly lower risk of mortality (p < 0.001) in all individuals, including those with MetS and/or a history of depression. CONCLUSIONS: Those with higher levels CRF had reduced mortality risk in the context of depression/MetS. Interventions that improve CRF could have substantial impact on the health of persons with depression/MetS.

Toward a very brief self-report to assess the core symptoms of depression (VQIDS-SR5 ).

OBJECTIVE: To develop a short, 5-item measure of the core symptoms of depression based on the 16-item Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR16 ) and to evaluate psychometric properties of this new measure (Very Quick Inventory of Depressive Symptomatology - Self-Report: VQIDS-SR5 ). METHOD: Using data from a convenience sample of the Combining Medications to Enhance Depression Outcomes (CO-MED) trial, we evaluated the psychometric properties of the VQIDS-SR5 , its sensitivity to change, and its comparability to the QIDS-SR16 and clinician-rated scales (QIDS-C16 and VQIDS-C5 ). RESULTS: The VQIDS-SR5 has a single-factor structure with an acceptable internal consistency (Cronbach's alpha: 0.67-0.81). The VQIDS-SR5 was as sensitive to change as its parent scale, then QIDS-SR16 and, detected change at an earlier time frame. Additionally, the VQIDS-SR5 was comparable to the QIDS-SR16 , QIDS-C16 , and VQIDS-C5 . CONCLUSION: The VQIDS-SR5 can effectively evaluate the core symptoms of depression during the course of treatment.

Modification of tumor cell exosome content by transfection with wt-p53 and microRNA-125b expressing plasmid DNA and its effect on macrophage polarization.

Exosomes are responsible for intercellular communication between tumor cells and others in the tumor microenvironment. These microvesicles promote oncogensis and can support towards metastasis by promoting a pro-tumorogenic environment. Modifying the exosomal content and exosome delivery are emerging novel cancer therapies. However, the clinical translation is limited due to feasibility of isolating and delivery of treated exosomes as well as an associated immune response in patients. In this study, we provide proof-of-concept for a novel treatment approach for manipulating exosomal content by genetic transfection of tumor cells using dual-targeted hyaluronic acid-based nanoparticles. Following transfection with plasmid DNA encoding for wild-type p53 (wt-p53) and microRNA-125b (miR-125b), we evaluate the transgene expression in the SK-LU-1 cells and in the secreted exosomes. Furthermore, along with modulation of wt-p53 and miR-125b expression, we also show that the exosomes (i.e., wt-p53/exo, miR-125b/exo and combination/exo) have a reprogramed global miRNA profile. The miRNAs in the exosomes were mainly related to the activation of genes associated with apoptosis as well as p53 signaling. More importantly, these altered miRNA levels in the exosomes could mediate macrophage repolarization towards a more pro-inflammatory/antitumor M1 phenotype. However, further studies, especially in vivo studies, are warranted to assess the direct influence of such macrophage reprogramming on cancer cells and oncogenesis post-treatment. The current study provides a novel platform enabling the development of therapeutic strategies affecting not only the cancer cells but also the tumor microenvironment by utilizing the 'bystander effect' through genetic transfer with secreted exosomes. Such modification could also support antitumor environment leading to decreased oncogenesis.

IL-1ß and BDNF are associated with improvement in hypersomnia but not insomnia following exercise in major depressive disorder.

Given the role of sleep in the development and treatment of major depressive disorder (MDD), it is becoming increasingly clear that elucidation of the biological mechanisms underlying sleep disturbances in MDD is crucial to improve treatment outcomes. Sleep disturbances are varied and can present as insomnia and/or hypersomnia. Though research has examined the biological underpinnings of insomnia in MDD, little is known about the role of biomarkers in hypersomnia associated with MDD. This paper examines biomarkers associated with changes in hypersomnia and insomnia and as predictors of improvements in sleep quality following exercise augmentation in persons with MDD. Subjects with non-remitted MDD were randomized to augmentation with one of two doses of aerobic exercise: 16 kilocalories per kilogram of body weight per week (KKW) or 4 KKW for 12 weeks. The four sleep-related items on the clinician-rated Inventory of Depressive Symptomatology (sleep onset insomnia, mid-nocturnal insomnia, early morning insomnia and hypersomnia) assessed self-reported sleep quality. Inflammatory cytokines (tumor necrosis factor-alpha, interleukin (IL)-1ß, IL-6) and brain-derived neurotrophic factor (BDNF) were assessed in blood samples collected before and following the 12-week intervention. Reduction in hypersomnia was correlated with reductions in BDNF (ρ = 0.26, P = 0.029) and IL-1ß (ρ = 0.37, P = 0.002). Changes in these biomarkers were not associated with changes in insomnia; however, lower baseline levels of IL-1ß were predictive of greater improvements in insomnia (F = 3.87, P = 0.050). In conclusion, improvement in hypersomnia is related to reductions in inflammatory markers and BDNF in persons with non-remitted MDD. Distinct biological mechanisms may explain reductions in insomnia.

A computational analysis of flanker interference in depression.

BACKGROUND: Depression is characterized by poor executive function, but - counterintuitively - in some studies, it has been associated with highly accurate performance on certain cognitively demanding tasks. The psychological mechanisms responsible for this paradoxical finding are unclear. To address this issue, we applied a drift diffusion model (DDM) to flanker task data from depressed and healthy adults participating in the multi-site Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC) study. METHOD: One hundred unmedicated, depressed adults and 40 healthy controls completed a flanker task. We investigated the effect of flanker interference on accuracy and response time, and used the DDM to examine group differences in three cognitive processes: prepotent response bias (tendency to respond to the distracting flankers), response inhibition (necessary to resist prepotency), and executive control (required for execution of correct response on incongruent trials). RESULTS: Consistent with prior reports, depressed participants responded more slowly and accurately than controls on incongruent trials. The DDM indicated that although executive control was sluggish in depressed participants, this was more than offset by decreased prepotent response bias. Among the depressed participants, anhedonia was negatively correlated with a parameter indexing the speed of executive control (r = -0.28, p = 0.007). CONCLUSIONS: Executive control was delayed in depression but this was counterbalanced by reduced prepotent response bias, demonstrating how participants with executive function deficits can nevertheless perform accurately in a cognitive control task. Drawing on data from neural network simulations, we speculate that these results may reflect tonically reduced striatal dopamine in depression.

ABCB1 (MDR1) predicts remission on P-gp substrates in chronic depression.

The hypothesis that allelic variation in the multidrug resistance-1 (MDR1 or ABCB1) gene encoding the P-glycoprotein (P-gp) blood-brain barrier efflux pump is associated with remission and side effects was tested in chronic major depression patients treated with P-gp substrates. In 83 patients from the REVAMP trial, frequency of and time to remission as well as side effects was tested among genotype groups at 6 ABCB1 single nucleotide polymorphisms (SNPs). These six SNPs are significantly associated with remission and time to remission, with minor allele carriers on rs2235040 and rs9282564 attaining statistical significance after controlling for the other ABCB1 SNPs. The six ABCB1 SNPs are also significantly associated with the average side effects. However, here common homozygotes on rs2235040 and rs9282564 demonstrated significantly higher side effects after controlling for the effects of the other ABCB1 SNPs. These findings confirm and extend previous observations that minor alleles of two ABCB1 SNPs predict remission to treatment with substrates and demonstrate that common homozygotes on these SNPs experience greater side effects. Results point to the potential importance of ABCB1 variation for personalized medicine approaches to treating depression.