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PURPOSE: We investigated the prevalence of financial toxicity in a population undergoing hematopoietic cell transplantation (HCT) evaluation and measured its impact on post-transplant clinical and health-related quality-of-life outcomes. MATERIALS AND METHODS: This was a prospective study in patients undergoing evaluation for allogeneic HCT between January 1, 2018, and September 23, 2020, at a large academic medical center. Financial health was measured via a baseline survey and the comprehensive score for financial toxicity-functional assessment of chronic illness therapy (COST-FACIT) survey. The cohort was divided into three groups: none (grade 0), mild (grade 1), and moderate-high financial toxicity (grades 2-3). Health-related quality of life outcomes were measured at multiple time points. Multivariate logistic regression analysis evaluated factors associated with financial toxicity. Kaplan-Meier curves and log-rank tests was used to evaluate overall survival (OS) and nonrelapse survival. RESULTS: Of 245 patients evaluated for transplant, 176 (71.8%) completed both questionnaires (median age was 57 years, 63.1% were male, 72.2% were White, and 39.2% had myelodysplastic syndrome, 38.1% leukemia, and 13.6% lymphoma). At initial evaluation, 83 (47.2%) patients reported no financial toxicity, 51 (29.0%) with mild, and 42 (23.9%) with moderate-high financial toxicity. Patients with financial toxicity reported significant cost-cutting behaviors, including reduced spending on food or clothing, using their savings, or not filling a prescription because of costs (P <.0001). Quality of life was lower in patients with moderate-high financial toxicity at 6 months (P =.0007) and 1 year (P =.0075) after transplant. Older age (>62; odds ratio [OR], 0.33 [95% CI, 0.13 to 0.79]; P =.04) and income ≥$60,000 in US dollars (USD) (OR, 0.17 [95% CI, 0.08 to 0.38]; P <.0001) were associated with lower odds of financial toxicity. No association was noted between financial toxicity and selection for transplant, OS, or nonrelapse mortality. CONCLUSION: Financial toxicity was highly correlated with patient-reported changes in compensatory behavior, with notable impact on patient quality of life after transplant. Prospective cohort study demonstrates a major impact of #FinancialToxicity in driving cost-cutting behaviors and worse quality of life in patients undergoing bone marrow transplant [ABSTRACT FROM AUTHOR]

Background Enterococcus intestinal domination (EID), a state of dysbiosis wherein enterococci comprise ≥30% abundance within the microbiota, has been associated with Enterococcus bacteremia, graft-versus-host disease, and mortality in the allogeneic hematopoietic stem cell transplant (allo HCT) population. The acute leukemia (AL) chemotherapy population includes patients receiving intensive chemotherapy, but not all patients go on to have an allo HCT. The impact of EID on outcomes including mortality in the AL chemotherapy population is unknown. Methods Microbiota composition from weekly stool samples was analyzed using 16S ribosomal RNA gene sequencing. Patients were analyzed in 2 cohorts: AL chemotherapy cohort and allo HCT cohort. α -diversity and richness were calculated. Kaplan-Meier analysis was used to analyze mortality. Results A total of 929 stool samples were collected from 139 patients. Both allo HCT and AL cohorts had a decline in α-diversity and richness over the course of treatment that tended not to return to baseline months later. EID was observed in at least 1 sample in 36% of allo HCT patients and 49% of AL patients. Patients with observed EID had lower α-diversity over time. Similar to the HCT cohort, AL patients with EID had reduced overall survival. We identified 4 other genera that were commonly found in ≥30% relative abundance within the microbiota, but none were associated with mortality. In fact, in allo HCT, Bacteroides abundance ≥30% was associated with improved survival. Conclusions EID is associated with increased all-cause mortality in HCT and AL cohorts. Unlike EID, relative abundance ≥30% by other genera is not associated with increased all-cause mortality. [ABSTRACT FROM AUTHOR]

Objective: Mitochondria are found in the extracellular space in rheumatoid arthritis (RA). However, whether mitochondria are a source of autoantigens in RA has not been carefully addressed. Thus, we undertook this study to investigate the presence and significance of antimitochondrial antibodies (AMAs) in patients with RA. Methods: AMAs were measured in serum samples from 3 cross‐sectional cohorts of RA patients (n = 95, n = 192, and n = 117) and healthy individuals (n = 38, n = 72, and n = 50) using a flow cytometry–based assay. Further, AMAs were detected using an anti–mitofusin‐1 (anti–MFN‐1) IgG enzyme‐linked immunosorbent assay and Western blot analysis. A longitudinal inception cohort, followed up for a median of 8 years, was used to study disease progression. Results: AMA levels were elevated in RA patients from all 3 cohorts as compared to healthy individuals (P < 0.001, P < 0.05, and P < 0.01), with a range of 14–26% positivity. Levels of anti–MFN‐1 antibodies correlated with AMA levels (r = 0.31, P = 0.006) and were elevated in RA patients as compared to healthy individuals (P < 0.001). The presence of AMAs was associated with erosive disease (P < 0.05) and interstitial lung disease (P < 0.01). Further, AMA levels were found to predict erosive disease (odds ratio [OR] 4.59, P = 0.006) and joint space narrowing (OR 3.08, P = 0.02) independent of anti–citrullinated protein antibodies. Finally, anti–MFN‐1 antibodies identified seronegative patients developing erosive disease (OR 9.33; P = 0.02). Conclusion: Our findings demonstrate the presence of novel autoantibodies targeting mitochondria in the setting of RA. AMAs were used to stratify patients based on disease phenotype and to predict development of erosive disease, including in patients with seronegative disease. Our results highlight the essential role of mitochondria in the pathogenesis of RA and suggest a possible benefit of therapies targeting mitochondrial‐mediated inflammation and clearance in these patients. [ABSTRACT FROM AUTHOR]

Objectives: Late Life Depression (LLD) is associated with persistent cognitive dysfunction even after depression symptoms improve. The present study was designed to examine cognitive outcomes associated with the pattern of depression severity change during psychotherapy intervention for LLD.Methods: 96 community-dwelling adults ages 65-91 with major depressive disorder completed 12 sessions of Problem-Solving Therapy at the University of California, San Francisco. Nonlinear trajectories of depression severity ratings using the Hamilton Depression Rating Scale were computed from multiple time points collected throughout the weekly psychotherapy intervention. Performance on measures of cognition (information processing speed, executive functioning, verbal learning, memory) was assessed at baseline and post-treatment. Linear mixed-effects models examined associations between nonlinear depression severity trajectories and post-treatment change in cognitive performance.Results: Broadly, different patterns of depression change during treatment were associated with improved cognition post-treatment. Greater and more consistent interval improvements in depression ratings were differentially associated with improvements in aspects of verbal learning, memory, and executive function post-treatment, while no associations were found with information processing speed.Conclusions: The heterogeneity of depression trajectories associated with improved cognitive outcomes suggests that the temporal pattern of depression response may impact specific cognitive processes distinctly. Results suggest that use of nonlinear depression severity trajectories may help to elucidate complex associations between the time course of depression response and cognitive outcomes of psychotherapy in LLD. These findings have important implications for identifying treatment targets to enhance clinical and cognitive outcomes of psychotherapy in LLD. [ABSTRACT FROM AUTHOR]

Background and Objective: Neurofeedback (NFB) provides real-time feedback about neurophysiological signals to patients, thereby encouraging modulation of pain-associated brain activity. This review aims to evaluate the effectiveness and safety of NFB in alleviating pain and pain-associated symptoms in chronic pain patients.Methods: MEDLINE, PUBMED, Web of Science and PsycINFO databases were searched using the strategy: ("Neurofeedback" OR "EEG Biofeedback" OR "fMRI Biofeedback") AND ("Pain" or "Chronic Pain"). Clinical trials reporting changes in pain following electroencephalogram (EEG) or functional magnetic resonance imaging (fMRI) NFB in chronic pain patients were included. Only Randomized-controlled trials (RCT), non-randomized controlled trials (NRCT) and case series were included. Effect size was pooled for all RCTs in a meta-analysis.Results: Twenty-one studies were included. Reduction in pain following NFB was reported by one high-quality RCT, five of six low-quality RCT or NRCT and 13 of 14 case-series. Pain reduction reported by studies ranged from 6% to 82%, with 10 studies reporting a clinically significant reduction in pain of >30%. The overall effect size was medium (cohen's d -0.76, 95% confidence interval -1.31 to -0.20). Studies were highly heterogeneous (Q [df = 5] = 18.46, p = .002, I2  = 73%). Improvements in depression, anxiety, fatigue and sleep were also seen in some studies. Common side-effects included headache, nausea and drowsiness. These generally did not lead to withdrawal of therapy except in one study.Conclusions: Neurofeedback is a safe and effective therapy with promising but largely low-quality evidence supporting its use in chronic pain. Further high-quality trials comparing different protocols is warranted to determine the most efficacious way to deliver NFB.Significance: Neurofeedback is a novel neuromodulatory approach which can be used to reduce the severity of pain and pain-associated symptoms such as sleep disturbances, mood disturbances, fatigue and anxiety in a number of chronic pain conditions. It has a potential to provide integrative non-pharmacological management for chronic pain patients with pain refractory to pharmacological agents with high side-effect profiles. Further high-quality double-blinded randomized sham-controlled trials are needed in order to fully explore the potential of this therapy. [ABSTRACT FROM AUTHOR]

Objective: To assess whether gene expression signatures associated with rheumatoid arthritis (RA) before pregnancy differ between women who improve or worsen during pregnancy, and to determine whether these expression signatures are altered during pregnancy when RA improves or worsens.Methods: Clinical data and blood samples were collected before pregnancy (T0) and at the third trimester (T3) from 11 women with RA and 5 healthy women. RA disease activity was assessed using the Clinical Disease Activity Index (CDAI). At each timepoint, RA-associated gene expression signatures were identified using differential expression analysis of RNA sequencing profiles between women with RA and healthy women.Results: Of the women with RA, 6 improved by T3 (RAimproved), 3 worsened (RAworsened),and 2 were excluded. At T0, mean CDAI scores were similar in both groups (RAimproved 11.2 ± 9.8; RAworsened 13.8 ± 6.7; Wilcoxon rank-sum test: P = 0.6). In the RAimproved group, 89 genes were differentially expressed at T0 (q < 0.05 and fold change ≥ 2) compared to healthy women. When RA improved at T3, 65 of 89 (73%) of these genes no longer displayed RA-associated expression. In the RAworsened group, a largely different RA gene expression signature (429 genes) was identified at T0. When RA disease activity worsened at T3, 207 of 429 (48%) genes lost their differential expression, while an additional 151 genes became newly differentially expressed.Conclusion: In our pilot dataset, pre-pregnancy RA expression signatures differed between women who subsequently improved or worsened during pregnancy, suggesting that inherent genomic differences may influence how pregnancy affects disease activity. Further, these RA signatures were altered during pregnancy as disease activity changed. [ABSTRACT FROM AUTHOR]

Background: Retrospective questionnaire and healthcare administrative data suggest reduced life expectancy in untreated hereditary hemorrhagic telangiectasia (HHT). Prospective data suggests similar mortality, to the general population, in Denmark's centre-treated HHT patients. However, clinical phenotypes vary widely in HHT, likely affecting mortality. We aimed to measure predictors of mortality among centre-treated HHT patients. HHT patients were recruited at 14 HHT centres of the Brain Vascular Malformation Consortium (BVMC) since 2010 and followed annually. Vital status, organ vascular malformations (VMs) and clinical symptoms data were collected at baseline and during follow-up (N = 1286). We tested whether organ VMs, HHT symptoms and HHT genes were associated with increased mortality using Cox regression analysis, adjusting for patient age, sex, and smoking status.Results: 59 deaths occurred over average follow-up time of 3.4 years (max 8.6 years). A history of anemia was associated with increased mortality (HR = 2.93, 95% CI 1.37-6.26, p = 0.006), as were gastro-intestinal (GI) bleeding (HR = 2.63, 95% CI 1.46-4.74, p = 0.001), and symptomatic liver VMs (HR = 2.10, 95% CI 1.15-3.84, p = 0.015). Brain VMs and pulmonary arteriovenous malformations (AVMs) were not associated with mortality (p > 0.05). Patients with SMAD4 mutation had significantly higher mortality (HR = 18.36, 95% CI 5.60-60.20, p < 0.001) compared to patients with ACVRL1 or ENG mutation, but this estimate is imprecise given the rarity of SMAD4 patients (n = 33, 4 deaths).Conclusions: Chronic GI bleeding, anemia and symptomatic liver VMs are associated with increased mortality in HHT patients, independent of age, and in keeping with the limited treatment options for these aspects of HHT. Conversely, mortality does not appear to be associated with pulmonary AVMs or brain VMs, for which patients are routinely screened and treated preventatively at HHT Centres. This demonstrates the need for development of new therapies to treat chronic anemia, GI bleeding, and symptomatic liver VMs in order to reduce mortality among HHT patients. [ABSTRACT FROM AUTHOR]

Introduction: In a preliminary case-control study, women with scleroderma more frequently reported having had hypertensive complications during pregnancy compared with healthy women.Material and Methods: To prospectively investigate this possible association, we conducted a nation-wide cohort analysis of a major hypertensive complication during pregnancy, namely preeclampsia, and later scleroderma. Analyses were based on Danish register-based birth and hospital contact data on preeclampsia and scleroderma. We followed 778,758 women from time of giving birth between 1978 and 2010 to end of follow-up, emigration, death, or scleroderma diagnosis, whichever occurred first. The association was evaluated by incidence rate ratios, obtained in Poisson regression models.Results: We report that preeclampsia is associated with a 69% significantly increased risk of later developing scleroderma.Conclusions: Though these findings do not impact clinical care directly, the association of preeclampsia with scleroderma underscores the significant relation of preeclampsia and other adverse pregnancy outcomes with later disease in women and should be included in patient counseling and education. [ABSTRACT FROM AUTHOR]

Background: A mother's infection with placental malaria (PM) can affect her child's susceptibility to malaria, although the mechanism remains unclear. The fetus acquires a small amount of maternal cells and DNA known as maternal microchimerism (MMc), and we hypothesized that PM increases MMc and that MMc alters risk of Plasmodium falciparum malaria during infancy.Methods: In a nested cohort from Muheza, Tanzania, we evaluated the presence and level of cord blood MMc in offspring of women with and without PM. A maternal-specific polymorphism was identified for each maternal-infant pair, and MMc was assayed by quantitative polymerase chain reaction. The ability of MMc to predict malaria outcomes during early childhood was evaluated in longitudinal models.Results: Inflammatory PM increased the detection rate of MMc among offspring of primigravidae and secundigravidae, and both noninflammatory and inflammatory PM increased the level of MMc. Detectable MMc predicted increased risk of positive blood smear but, interestingly, decreased risk of symptomatic malaria and malaria hospitalization.Conclusions: The acquisition of MMc may result in increased malaria infection but protection from malaria disease. Future studies should be directed at the cellular component of MMc, with attention to its ability to directly or indirectly coordinate anti-malarial immune responses in the offspring. [ABSTRACT FROM AUTHOR]

Objective: To compare fetal microchimerism (FMc) in pregnancies with uncomplicated vaginal delivery (VD) versus caesarean delivery (CD).Design: Prospective cohort study.Setting: University of Washington and Fred Hutchinson Cancer Research Center, USA.Population: Women delivering singleton pregnancies without pertinent antenatal complications with uncomplicated deliveries (n = 36).Methods: We collected maternal predelivery, postdelivery and umbilical cord blood for each mother-baby pair. Following maternal and fetal genotyping, FMc was measured with quantitative polymerase chain reaction assays targeting fetus-specific polymorphisms. Quantification of FMc is expressed as genome equivalents (gEq) of fetal DNA/100 000 total gEq tested. FMc detection was evaluated by logistic regression while controlling for total number of cell equivalents tested and clinically relevant covariates. FMc concentrations were compared using negative binomial regression while controlling for the same covariates and predelivery FMc positivity.Main Outcome Measure: Detection and concentration of FMc by mode of delivery.Results: Twenty-four mother-baby pairs had a VD and 12 had a CD. Postdelivery FMc detection was higher following CD than after VD (58.3% versus 16.7%, P = 0.02). After controlling for covariates, the likelihood of postdelivery FMc detection was almost nine-fold higher after CD than VD (odds ratio 8.8, 95% CI 1.6-47.6; P = 0.01). With respect to postdelivery FMc concentration, the detection rate ratio for CD versus VD in the adjusted negative binomial regression model was 14.7 (95% CI 3.2-66.8; P = 0.001).Conclusion: Postdelivery peripheral FMc detection and concentration are significantly higher after CD than after VD. As FMc is associated with long-term maternal health, our findings suggest that the mode of delivery may impact this risk.Tweetable Abstract: Greater fetal microchimerism found in maternal blood following caesarean delivery compared with vaginal delivery. [ABSTRACT FROM AUTHOR]

Objective: Little is known about mental health service use by adults with prior suicidal behavior and current mood or anxiety disorders. This study determined nationally representative prevalence estimates of current mental health service use by these adults, examining racial-ethnic, age, and gender differences.Methods: Service use across the life course was examined with Collaborative Psychiatric Epidemiology Survey data from 1,139 adults with a history of suicidal behavior and current mood or anxiety disorders.Results: Overall service use was 47.3%. Across the life course, African Americans showed increasing service use that paralleled use by non-Hispanic whites, Hispanics, and others, whereas use by these three groups decreased in the latter half of the life course (p interaction=.01).Conclusions: Adults with prior suicidal behavior and current mood or anxiety disorders have low mental health service use. Findings of racial-ethnic disparities in use can help identify those in need of care. [ABSTRACT FROM AUTHOR]

Natural acquisition of small amounts of foreign cells or DNA, referred to as microchimerism, occurs primarily through maternal-fetal exchange during pregnancy. Microchimerism can persist long-term and has been associated with both beneficial and adverse human health outcomes. Quantitative microchimerism data present challenges for statistical analysis, including a skewed distribution, excess zero values, and occasional large values. Methods for comparing microchimerism levels across groups while controlling for covariates are not well established. We compared statistical models for quantitative microchimerism values, applied to simulated data sets and 2 observed data sets, to make recommendations for analytic practice. Modeling the level of quantitative microchimerism as a rate via Poisson or negative binomial model with the rate of detection defined as a count of microchimerism genome equivalents per total cell equivalents tested utilizes all available data and facilitates a comparison of rates between groups. We found that both the marginalized zero-inflated Poisson model and the negative binomial model can provide unbiased and consistent estimates of the overall association of exposure or study group with microchimerism detection rates. The negative binomial model remains the more accessible of these 2 approaches; thus, we conclude that the negative binomial model may be most appropriate for analyzing quantitative microchimerism data. [ABSTRACT FROM AUTHOR]

Objective Systemic sclerosis (SSc) is a rare disease that is particularly uncommon in children. Specific HLA alleles have been associated with SSc in adults. This study was undertaken to investigate HLA class II alleles in juvenile-onset SSc. Methods DRB1, DQA1, and DQB1 alleles were determined by DNA-based HLA typing. Analyses were conducted comparing Caucasian patients with juvenile-onset SSc (n = 76) to healthy Caucasian controls (n = 581). Results Initial analyses focused on HLA class II associations previously reported in adult Caucasian patients with SSc. The frequency of DRB1*11 was not significantly increased in juvenile-onset SSc (22.4% of patients with juvenile-onset SSc versus 17.6% of controls; odds ratio [OR] 1.35, P = 0.34), nor were the specific DRB1*11:01 or *11:04 alleles. DQA1*05, a risk factor previously identified in adult men with SSc, was increased in patients with juvenile-onset SSc versus controls (57.9% versus 44.1%; OR 1.76, P = 0.027), as was DRB1*03 (34.2% versus 22.5%; OR 1.79, P = 0.031). Secondary analyses of all DRB1 allele groups revealed an association with DRB1*10 (10.5% of patients with juvenile-onset SSc versus 1.5% of controls; OR 7.48, P = 0.0002). As this is a new observation, correction was made for multiple comparisons of 13 different DRB1 allele groups; results nevertheless remained significant ( P = 0.003). Also, a lower frequency of DRB1*01 was observed in patients with juvenile-onset SSc who were younger at disease onset (OR 0.06, P = 0.01) and in those with antibodies to topoisomerase (OR 0.14, P = 0.024). Conclusion Associations of HLA alleles with juvenile-onset SSc differed from associations with SSc in women, but were similar to associations with SSc in men. Additionally, a novel association with DRB1*10 was observed in children. The greatest proportion of genetic risk of SSc is contributed by the HLA complex, and the current study reveals the importance of the association of HLA class II genes in juvenile-onset SSc. [ABSTRACT FROM AUTHOR]

Background: Due to the clinical challenges of treatment-resistant depression (TRD), we evaluated the efficacy of mindfulness-based cognitive therapy (MBCT) relative to a structurally equivalent active comparison condition as adjuncts to treatment-as-usual (TAU) pharmacotherapy in TRD.Methods: This single-site, randomized controlled trial compared 8-week courses of MBCT and the Health Enhancement Program (HEP), comprising physical fitness, music therapy and nutritional education, as adjuncts to TAU pharmacotherapy for outpatient adults with TRD. The primary outcome was change in depression severity, measured by percent reduction in the total score on the 17-item Hamilton Depression Rating Scale (HAM-D17), with secondary depression indicators of treatment response and remission.Results: We enrolled 173 adults; mean length of a current depressive episode was 6.8 years (SD = 8.9). At the end of 8 weeks of treatment, a multivariate analysis showed that relative to the HEP condition, the MBCT condition was associated with a significantly greater mean percent reduction in the HAM-D17 (36.6 vs. 25.3%; p = 0.01) and a significantly higher rate of treatment responders (30.3 vs. 15.3%; p = 0.03). Although numerically superior for MBCT than for HEP, the rates of remission did not significantly differ between treatments (22.4 vs. 13.9%; p = 0.15). In these models, state anxiety, perceived stress and the presence of personality disorder had adverse effects on outcomes.Conclusions: MBCT significantly decreased depression severity and improved treatment response rates at 8 weeks but not remission rates. MBCT appears to be a viable adjunct in the management of TRD. [ABSTRACT FROM AUTHOR]

Background: Nurses consistently report the highest levels of job stress among all health professionals. To best prepare students for such a high-stress profession, insights into the onset of stress is warranted, especially with the literature supporting that nursing students experience significant stress during their education. Method: This study sought to explore the sources of stress among nursing students and to compare stress levels and selected mental health indicators between nursing students and the general student body using the paper-and-pencil version of the National College Health Assessment II. Results: Nursing students were found to have significantly more stress, anxiety, sleep disturbances, and stress-related illnesses than the general student body. Conclusion: The findings highlight the importance of selfcare and stress management skills education in nurse preparatory programs for use in both academic preparation and in future careers. [ABSTRACT FROM AUTHOR]

Saliva plays a major role in maintaining oral health. Patients with salivary hypofunction exhibit difficulty in chewing and swallowing foods, tooth decay, periodontal disease, and microbial infections. At this time, treatments for hyposalivation are limited to medications (e.g., muscarinic receptor agonists: pilocarpine and cevimeline) that induce saliva secretion from residual acinar cells as well as artificial salivary substitutes. Therefore, advancement of restorative treatments is necessary to improve the quality of life in these patients. Our previous studies indicated that salivary cells are able to form polarized 3-dimensional structures when grown on growth factor-reduced Matrigel. This basement membrane is rich in laminin-III (L1), which plays a critical role in salivary gland formation. Mitotically inactive feeder layers have been used previously to support the growth of many different cell types, as they provide factors necessary for cell growth and organization. The goal of this study was to improve salivary gland cell differentiation in primary cultures by using a combination of L1 and a feeder layer of human hair follicle-derived mesenchymal stem cells (hHF-MSCs). Our results indicated that the direct contact of mouse submandibular (mSMG) cell clusters and hHF-MSCs was not required for mSMG cells to form acinar and ductal structures. However, the hHF-MSC conditioned medium enhanced cell organization and multilumen formation, indicating that soluble signals secreted by hHF-MSCs play a role in promoting these features. [ABSTRACT FROM AUTHOR]

Background: Less than half of patients with major depressive disorder (MDD) respond to their first antidepressant trial. Our understanding of the underlying mechanisms of selective serotonin reuptake inhibitors (SSRIs) remains poor, and there is no reliable method of predicting treatment response.Methods: Thirty-seven MDD subjects and 41 healthy controls, somatically healthy and medication-free for at least six weeks, were recruited, and plasma serotonin (5-HT) levels were assessed at baseline. Twenty-six of the MDD subjects were then treated in an open-label manner with clinically appropriate doses of sertraline for 8 weeks, after which plasma 5-HT levels were again assessed. Response to treatment was defined as an improvement of 50% or more on the Hamilton Depression Rating Scale.Results: Non-responders to sertraline treatment had significantly lower pre-treatment 5-HT levels compared to both healthy controls and responders (F = 4.4, p = 0.004 and p = 0.036, respectively). There was a significant decrease in 5-HT levels over treatment in all MDD subjects (t = 6.2, p = 0.000003). The decrease was significantly more prominent in responders compared to non-responders (t = 2.1, p = 0.047). There was no significant difference in post-treatment 5-HT levels between responders and non-responders.Limitations: The study had a modest sample size. 5-HT levels in plasma may not reflect 5-HT levels in the brain.Conclusions: The results indicate that SSRI response may be facilitated by adequate baseline plasma 5-HT content and that successful SSRI treatment is associated with greater decreases in circulating 5-HT. Plasma 5-HT content may be a predictor of SSRI treatment outcome. Potential underlying mechanisms are discussed. [ABSTRACT FROM AUTHOR]