History Of Major Depressive Disorder Research Articles

RELATIONSHIP OF HAIR CORTISOL CONCENTRATION WITH HISTORY OF PSYCHOSIS, NEUROPSYCHOLOGICAL PERFORMANCE, AND EVERYDAY FUNCTIONING IN REMITTED LATER-LIFE MAJOR DEPRESSIVE DISORDER

Introduction Psychotic features are more prevalent in older adults with depression than in younger depressed adults. Psychotic major depressive disorder (PMD) is associated with poorer neuropsychological performance and poorer everyday functioning, in both acute and remitted states, compared with non-psychotic major depressive disorder (NPMD). In addition, PMD is also associated with more pronounced dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, including elevated cortisol levels, but it is not known whether this difference between PMD and NPMD persists in remission. The goal of this exploratory study was to test the hypothesis that a history of psychotic features, poorer neuropsychological performance, and poorer everyday functioning were associated with higher cortisol levels in sustained remission of major depressive disorder. If confirmed, it could suggest a possible mechanism for neuropsychological and functional impairment in remitted PMD. In order to examine the relationship between sustained HPA dysfunction in remission and the aforementioned variables, we measured hair cortisol concentration (HCC), a measure of longer-term cortisol exposure. Methods This study used a cross-sectional design and included 60 participants aged 50 years or older with a history of major depressive disorder (n = 17 with NPMD and n = 43 with PMD) in sustained remission and 36 non-psychiatric comparison participants. Hair samples were collected using standardized methods and cortisol concentrations were determined from the first 3-cm hair segment most proximal to the scalp, or from as much hair as was available for participants with shorter hair. This hair segment represents the hair growth over the 3-month period prior to the sampling. HCC was measured in a research laboratory with extensive experience in this analysis using a validated high sensitivity enzyme immunoassay (EIA) that is standard in the field. In order to examine the relationships between HCC and i) history of psychotic features, ii) neuropsychological performance (processing speed, executive function, and verbal memory), and iii) everyday functioning (participant-report general functioning and observer-rated IADL performance), we performed three sets of correlation analyses, one for each variable of interest (point biserial for psychosis history and HCC; Pearson's r for neuropsychological and functional measures). We calculated effect sizes and 95% confidence limits in order to compare HCC results between patient and non-psychiatric comparison groups. HCC data were highly skewed and were log transformed for all analyses. Results NPMD and PMD groups had mean (SD) HCCs of 18.86 (32.97) pg/mg and 12.48 (11.26) pg/mg, respectively. The correlation between HCC and history of psychosis was weak (r = -0.02), as were the correlations between HCC and the neuropsychological measures (r ranging between -0.11 and 0.1). The correlations between HCC and i) IADL performance (r = -0.04) and ii) general functioning (r = -0.074) were also weak. None of these correlations were statistically significant. The mean (SD) HCC for non-psychiatric comparison subjects was 13.86 (20.06) pg/mg. Both effect sizes for the difference between the clinical and non-psychiatric comparison groups were small (0.26 for NPMD versus Comparison group and 0.25 for PMD versus Comparison group). Conclusions This is the first study to assess HCC in PMD and to examine the relationship between HCC and cognition and between HCC and everyday functioning in MDD. We did not find a correlation between HCC and history of psychosis, neuropsychological performance, or functioning in later-life patients with MDD in sustained remission. Further, there was no substantial difference in mean HCC between the patient and non-psychiatric comparison group. There is variability in the literature regarding HCC in MDD and regarding the relationship between HPA-axis function and neuropsychological performance in remitted MDD. Our findings will be discussed in this context. This research was funded by This study was funded by a research grant from the University Health Network Centre for Mental Health ($14,000)

Maternal depression and children’s false belief understanding

AbstractChildren of depressed mothers show substantial social impairment, which increases their risk for developing depression. Theory of mind understanding forms the basis of social functioning, and is impaired in children of currently depressed mothers. Models of risk emphasize that a history of any maternal depression confers risk to later psychopathology. Therefore, we tested a novel model of the impact of lifetime maternal depression on children’s false belief understanding that accounts for three primary factors that scaffold this understanding: maternal mental state talk, and children’s executive functioning and language abilities. Children aged 41–48 months with a maternal lifetime history of major depressive disorder (MDD; n = 19) performed significantly more poorly on the false belief battery compared to those without (n = 44). Further, lower levels of mental state talk, child executive functioning, and child language ability were significantly associated with poorer false belief scores. However, the relation between maternal MDD and children’s false belief performance was not mediated by any of these factors. These results indicate that maternal depression predicts poorer false belief understanding independently of other crucial scaffolding variables, and may be a social cognitive mechanism underlying the intergenerational transmission of depression.

Examining the Link Between Cardiovascular Risk Factors and Neuropsychiatric Symptoms in Mild Cognitive Impairment and Major Depressive Disorder in Remission.

Cardiovascular risk factors (CVRFs) have been linked to both depression and cognitive decline but their role in neuropsychiatric symptoms (NPS) has yet to be clarified. Understanding the role of CVRFs in the etiology of NPS for prospective treatments and preventive strategies to minimize these symptoms. We examined the distribution of NPS using the Neuropsychiatric Inventory (NPI) scores in three cohorts from the Prevention of Alzheimer's Dementia with Cognitive Remediation Plus Transcranial Direct Current Stimulation in Mild Cognitive Impairment and Depression (PACt-MD) study: older patients with a lifetime history of major depressive disorder (MDD) in remission, patients with mild cognitive impairment (MCI), and patients with combined MCI and MDD. We also examined the link between individual NPS and CVRFs, Framingham risk score, and Hachinski ischemic score in a combined sample. Analyses were based on a sample of 140 subjects, 70 with MCI, 38 with MCI plus MDD, and 32 with MDD. There was no effect of age, gender, education, cognition, or CVRFs on the presence (NPI >1) or absence (NPI = 0) of NPS. Depression was the most prevalent affective NPS domain followed by night-time behaviors and appetite changes across all three diagnostic groups. Agitation and aggression correlated negatively while anxiety, disinhibition, night-time behaviors, and irritability correlated positively with CVRFs (all p-values <0.05). Other NPS domains showed no significant association with CVRFs. CVRFs are significantly associated with individual NPI sub-scores but not with total NPI scores, suggesting that different pathologies may contribute to different NPS domains.

Prospective associations among objectively and subjectively assessed sleep and the metabolic syndrome

ObjectiveSubjective sleep disturbances have been associated with greater risk for concurrent and incident metabolic syndrome (MetS). Previous studies have not examined prospective associations among polysomnography-assessed sleep and the MetS, despite knowledge that self-reported sleep is subject to reporting bias, and that subjectively and objectively assessed sleep are weakly correlated. MethodIn the current study, objectively-assessed (polysomnography) and subjectively-assessed (Pittsburgh Sleep Quality Index, PSQI) sleep was measured in 145 adults at two timepoints, separated by 12–30 years. A continuous measure of the MetS was assessed at the second time point. Statistical analyses were adjusted for age, sex, lifetime history of major depressive disorder, follow-up time, and apnea-hypopnea index. ResultsPolysomnography-assessed sleep duration, latency, efficiency, and slow wave sleep were not significantly prospectively associated with the MetS (ps ≥ 0.16). Self-reported longer sleep latency was prospectively associated with higher MetS scores in unadjusted (β = 0.29, p = 0.002) and adjusted models (β = 0.25, p = 0.009). Longer sleep latency was associated with higher fasting glucose levels (β = 0.47, p < 0.001). ConclusionOur study provides evidence that subjective and objective measures of sleep may differ in their ability to prospectively predict MetS.

Dysregulated behavioral responses to hedonic probes among youth with depression histories and their high-risk siblings.

Affect dysregulation in response to rewarding stimuli has been proposed as a vulnerability factor for major depressive disorder (MDD). However, it remains unclear how affective behavioral dynamics may be altered among individuals who are at high risk for depression but not currently depressed. We examined the dynamics of affective facial behavior during hedonic probes among 3 groups of adolescents: remitted probands who had histories of childhood-onset MDD (n = 187), never-depressed siblings of probands (high familial risk; n = 207), and healthy controls (n = 166). Participants' happy and sad facial expressions were coded during 3 hedonic laboratory tasks: receiving a preferred prize, describing a positive autobiographical memory, and watching a humorous film. Happy and sad behavioral dynamics were indexed by mean level- and time-dependent reactivity, variability (mean of the squared successive differences), and inertia (autocorrelation). Relative to controls, probands and siblings exhibited a more rapid decrease in happy behaviors, and probands exhibited higher inertia of sad behaviors during hedonic probes. Both probands and siblings exhibited lower inertia of sad behaviors while receiving a desired prize, which highlights the importance of context variation in testing hypotheses. Overall, our study provides new evidence that hedonic behavioral dysregulation, as reflected in dynamic facial behavior, may highlight depression vulnerability. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Genome-wide association study identifies a novel locus associated with psychological distress in the Japanese population

Major depressive disorder (MDD) is a common and disabling psychiatric disorder. A recent mega analysis of genome-wide association studies (GWASs) identified 44 loci associated with MDD, though most of the genetic etiologies of the MDD/psychological distress remain unclear. To further understand the genetic basis of MDD/psychological distress, we conducted a GWAS in East Asia with more than 10,000 participants of Japanese ancestry who had enrolled in a direct-to-consumer genetic test. After quality control on the genotype data, 10,330 subjects with a total of 8,567,708 imputed SNPs were eligible for the analysis. The participants completed a self-administered questionnaire on their past medical history and health conditions that included the 6-item Kessler screening scale (K6 scale) for psychological distress (cut-off point of 5) and past medical history of MDD, resulting in 3981 subjects assigned to “psychologically distressed group” [cases], and the remaining 6349 subjects were assigned to the “non-psychologically distressed group” [controls]. In this GWAS, we found an association with genome-wide significance at rs6073833 (P = 7.60 × 10−9) in 20q13.12. This is, to the best of our knowledge, the first large-scale GWAS for psychological distress using data from direct-to-consumer (DTC) genetic tests in a population of non-European-ancestry, and the present study thus detected a novel locus significantly associated with psychological distress in the Japanese population.

Parenting in Context: Associations of Parental Depression and Socioeconomic Factors with Parenting Behaviors

The current study examined the unique and combined associations of parental depression and socioeconomic disadvantage with parenting behaviors in parents with a history of depression. A sample of 180 parents with a history of major depressive disorder and one of their children (ages 9–15 years old) completed a videorecorded conversation task and parents completed self-report measures of depression symptoms and socioeconomic variables (parental education, income, marital status). Parental depression symptoms and socioeconomic variables were related to higher levels of harsh and withdrawn parenting in univariate analyses. In multivariate analyses, socioeconomic factors were significant predictors of both types of disrupted parenting. However, while parental depression symptoms remained a significant predictor of withdrawn parenting, they no longer significantly predicted harsh parenting when socioeconomic factors were included in multivariate analyses. Results highlight the importance of considering the economic context of families, particularly the impact of socioeconomic disadvantage on parenting behaviors in a sample of depressed parents.

A cluster randomized controlled trial of an online psychoeducational intervention for people with a family history of depression

BackgroundPeople with a family history of major depressive disorder (MDD) or bipolar disorder (BD) report specific psychoeducational needs that are unmet by existing online interventions. This trial aimed to test whether an interactive website for people at familial risk for depression (intervention) would improve intention to adopt, or actual adoption of, depression prevention strategies (primary outcome) and a range of secondary outcome measures.MethodsIn this cluster randomised trial, primary care practises were randomised to either provide the link to the intervention or the control website. Primary health care attendees were invited by letter to opt into this study if they had at least one first-degree relative with MDD or BD and were asked to complete online questionnaires at baseline and 2-week follow-up.ResultsTwenty general practices were a randomized, and 202 eligible patients completed both questionnaires. Thirty-nine (19.3%) of participants were male and 163 (80.7%) female. At follow-up, compared to controls, the intervention group: (i) were more likely to intend to undergo, or to have actually undergone, psychological therapies (OR = 5.83, 95% CI: 1.58–21.47, p = .008); (ii) had better knowledge of depression risk factors and prevention strategies (mean difference = 0.47, 95% CI: 0.05–0.88, p = .029); and (iii) were more likely to accurately estimate their lifetime risk of developing BD (mean difference = 11.2, 95% CI: -16.52– -5.73, p < .001). There were no statistically significant between-group differences in change from baseline to follow up for any of the remaining outcome measures (Patient Health Questionnaire, Perceived Devaluation-Discrimination Questionnaire and Perceived Risk of Developing MDD).ConclusionThe opt-in nature of the study may have led to participation bias, e.g. underrepresentation of males, and hence may limit generalisability to the broader population at familial risk for depression. This is the first website internationally focusing specifically on informational needs of those at familial risk of depression. Our interactive website can play an important role in improving the outcomes of individuals at familial risk for depression. Testing the intervention in other settings (e.g. psychology, psychiatry, genetic counselling) appears warranted.Trial registrationThe study was prospectively registered with the Australian and New Zealand Clinical Trials Group (Registration no: ACTRN12613000402741).

Sex-specific association of depressive disorder and transient emotional states with alcohol consumption in male and female alcoholics

BackgroundWe assessed the impact of comorbid depression and anxiety disorders as well as positive and negative emotional states on alcohol consumption in alcohol dependent men and women. MethodsPer day alcohol consumption during 90 days before enrolment was assessed by the Time Line Follow Back (TLFB) in 287 men and 156 women meeting DSM-IV-TR criteria for alcohol dependence. Propensity to drink in negative/positive emotional states was assessed using the Inventory of Drug Taking Situations (IDTS). Psychiatric comorbidities, including major depressive disorder (MDD), substance-induced depression (SID), anxiety disorders (AnxD), or substance-induced anxiety (SIA) were identified by Psychiatric Research Interview of Substance and Mood Disorders (PRISM). ResultsIn the combined group, increased number of drinks per day and number of heavy drinking days correlated with increased IDTS scores (all p < 0.0001), while the lifetime history of MDD was associated with fewer drinking days (p = 0.045) but not average number of drinks per day. Male sex was associated with higher alcohol consumption per day (p < 0.0001), but not with the number of drinking days (p > 0.05). Lifetime MDD history was associated with less drinking days (p = 0.0084) and less heavy drinking days (p = 0.021) in alcohol dependent men, while current MDD was associated with higher alcohol use per day in alcohol dependent women (p = 0.044). ConclusionsOur findings suggest that emotional states and lifetime MDD history have sex-specific impact on alcohol use in alcohol dependent men and women. The mechanisms underlying these findings and their relevance to treatment outcomes need to be examined in future studies.

M41 - DEPRESSION, INFLAMMATION, AND METABOLIC RISK: A GENETICALLY-INFORMED EXPLORATORY STUDY

Background Depression is a highly prevalent psychiatric disorder, which has been observed to have greater-than-expected comorbidity with metabolic and inflammatory disorders. Although standard observational study designs encounter limitations when assessing the directionality of the relationships underlying the comorbidities, twin studies offer a means to resolve competing explanations of comorbidity. The purpose of this study is to examine the relationship between depression and biomarkers associated with inflammation and metabolic risk by examining patterns of correlation in monozygotic twin pairs with different depression histories. Methods The sample consisted of 45 monozygotic twin pairs (mean age: 52.8, 69% female, 76% white) assessed twice over a 6-month period. Lifetime history of Major Depressive Disorder (MDD) was assessed using the Diagnostic Interview Schedule. Biological measures included peripheral leukocyte gene expression (data not yet available), hemoglobin A1c (HbA1c, a measure indicative of recent blood sugar levels), and two markers of systemic inflammation, C-reactive Reactive Protein (CRP), and interleukin-6 (IL-6). Intraclass correlation coefficients (ICC) were calculated across members of each twin pair, and within-individual across timepoints. Biomarker levels were also compared between members of twin pairs discordant for MDD, and with twins from pairs in which neither member had a history of MDD. Results Of the 40 pairs with known MDD history, 13 (32.5%) had no history of MDD in either member, 14 (35%) were discordant for MDD, and 13 (32.5%) had a lifetime history of MDD in both twins. HbA1c showed a low ICC between twins (0.363), but a high ICC within individuals over time (0.873). CRP had a low ICC both between twins (0.189) and within individuals over time (0.174). IL-6 had a moderately high ICC both between twins (0.571) and within individuals over time (0.691). In MDD-discordant pairs, the twins with MDD had higher median HbA1c (5.55%) than their non-MDD co-twins (5.45%), while twins from MDD-free pairs were not notably different (5.50%). Change in HbA1c was highest in the twin with MDD in the discordant pairs (0.25%), followed by their non-MDD co-twins (0.20%), and lowest in MDD-free pairs (0.10%). In discordant twin pairs, the twin with a history of MDD had lower median CRP (1810.95 ng/ml) than the twin without MDD (2683.98 ng/ml), while the lowest CRP was found in MDD-free pairs (827.213 ng/ml). For discordant pairs, the twin with MDD had higher median IL-6 (1.53 pg/ml) than their non-MDD co-twins (1.08 pg/ml), and twins from MDD-free pairs had the lowest IL-6 (0.658 pg/ml). Discussion The differing patterns in ICC suggest that HbA1c is greatly influenced by individual-specific environmental factors and moderately influenced by genetic or shared environmental factors. In contrast, circulating levels of CRP are largely influenced by short-term environmental factors. Finally, circulating levels of IL-6 have a notable contribution from genetic or environmental factors shared between twins. Levels of IL-6 and change in HbA1c over time followed a pattern of highest values in twins with MDD, their non-MDD co-twin, followed by twins from MDD-free pairs. This is consistent with the hypothesis that MDD has an influence on these biomarkers, but much of that influence is driven by genetic liability for MDD. These preliminary results demonstrate the value of longitudinal studies using monozygotic twins, although further analysis is needed.

SU39 - GENOME WIDE ASSOCIATION STUDY OF TREATMENT RESPONSE TO COGNITIVE BEHAVIORAL THERAPY FOR DEPRESSION

Background Major Depressive Disorder (MDD) is a serious, but treatable, disorder where Cognitive Behavioral Therapy (CBT) is a first line treatment. However, a significant number of patients (40–60%) are not responding to treatment and understanding more about the disorder and who responds to treatment is crucial to improve outcomes. In the past year, there have been marked advances in the genomics of MDD thanks to large consortia GWAS efforts. Here we leverage summary statistics derived from the latest MDD GWAS in order to test whether individual MDD polygenic risk scores (PRS) associate with baseline severity and CBT response in a sample of 971 MDD cases undergoing internet-based CBT (iCBT). Our aim is to calculate MDD Polygenic Risk Scores (PRS) and examine their relationship with a key measure of disease severity and treatment response with longitudinal follow up data. Methods We collected DNA from 971 Swedish MDD cases (66% female) who took part in a 12-week course of iCBT. The primary outcome variable was the Montgomery Asberg Depression Rating Scale – Self-rating (MADRS-S) and was measured pre-treatment, weekly, post treatment and at 6 months follow-up. For genotyping, the Illumina Global Screening Array (GSA) was used for the 971 samples. For population-specific controls, we will calculate MDD PRS for a set of 3,000 Swedish individuals with no history of MDD. We use the latest MDD summary statistics to calculate PRS for each individual to examine the relationship between polygenic load and a key measure of disease severity and treatment response. Further, we calculate PRS for a range of other traits which may influence disease severity or treatment response: neuroticism, bipolar disorder, subjective well-being and educational attainment. Results We will present results detailing the relationship between MDD PRS and disease severity (baseline MADRS) as well as treatment response (change in MADRS following iCBT) and treatment adherence. Further, we will present results demonstrating how PRS for a range of other traits influence disease severity or treatment response. Discussion In other psychiatric disorders, such as schizophrenia, polygenic risk score analyses and treatment response of pharmacological interventions have been investigated with interesting outcomes. In our future work, we will contrast genetic predictors with non-genetic predictors derived from the Swedish registers (e.g. pre- and perinatal risk factors), to try to understand even more about the biological underpinnings of MDD and response to treatment. We believe performing these analyses will bring us one step closer to determining whether genomics can help personalize MDD treatment.

SU33 - A GENOME-WIDE ASSOCIATION STUDY IDENTIFIES A NOVEL LOCUS ASSOCIATED WITH DEPRESSIVE STATE IN THE JAPANESE POPULATION

Background Major Depressive Disorder (MDD) is a common and disabling psychiatric disorder. MDD is a multifactorial disorder with multiple genetic and environmental factors with relatively small effects. To date, only a small number of loci have been identified to be significantly (P Methods To further understand of the genetic basis of MDD, we conducted a Genome-Wide Association Study (GWAS) in East Asia with more than ten thousand participants of Japanese ancestry. Participants completed a self-administered questionnaire on their medical history and health conditions that included the 6-item Kessler screening scale (K6) for depressive state (cut-off point 4/5; 4,071, depressive group [cases]; 6,749, non-depressive group [controls]). The genomic DNA of the participants was extracted from saliva and was genotyped for Single-Nucleotide Polymorphisms (SNPs) using Illumina HumanCore BeadChip (about 300,000 SNPs with add-on 5,000 SNPs). SNPs were excluded if the call rate was Results A genome-wide significant association (P=8.8E-9) was observed for a locus in chromosome 20, upstream of WAP-type four-disulfide core 10B (WFDC10B), a member of the WFDC domain family, which has been reported to play a regulatory role in inflammation. On the other hand, there were no SNPs with genome-wide significant associations with past medical history of MDD (898, diagnosed group [cases]; 9,992, non-diagnosed group [controls]). Discussion This is, to the best of our knowledge, the first large-scale GWAS using data from direct-to-consumer (DTC) genetic tests carried out in a population not of European-ancestry. The present study detected a novel locus significantly associated with depressive state, but further research is necessary to replicate the current findings. This study suggests that DTC genetic tests with self-reported trait data can contribute to revealing genetic basis for MDD.

SA65 - IDENTIFYING VARIANTS IN NF1A GENE TO BE ASSOCIATED WITH SEASONAL PATTERN AND SUSCEPTIBILITY FOR DEPRESSION THROUGH A CANDIDATE GENE APPROACH

Background Seasonal Pattern (SP) was reported in depressive patients of both Bipolar Disorder (BD) and Major Depressive Disorder (MDD). In this study, we aimed to investigate genetic contributions of seasonal pattern of major depressive episodes in both BD and MDD patients, including genes in relevant biological pathways indicated in previous studies. To further clarify the roles of the variants in depression, we conducted analyses using a case-control study design to examine whether the genetic variants for SP also possess effects on susceptibility to depression. Methods We recruited 472 BD (83%) and MDD (17%) patients in Taiwan. SP of depressive episode were defined according to interview questions as “Which season do you feel the worst?” in their first, the most serious, and the most recent episode within a year. Subjects answered a specific season in two of the three episode categories were considered SP+, while others were categorized as non-SP (SP-). The other dataset for depression was obtained from the Taiwan biobank with about 10,000 people. Cases were defined by self-report MDD history or having the sum-score greater than 3 in the Patient Health Questionnaire-4. We examined 15 genes (824 single nucleotide variants) including the melatonin pathway (MTNR1a, MTNR1b, AANAT), serotonin pathway (TPH2, HTR2A, HTR2B, SLC6A4), circadian feedback loop (NPAS2, CRY2, ARNTL, ARNTL2, RORA, RORB, PER) and NF1A gene that identified from a previous genome-wide association study of seasonal mania. Association analyses were performed by multivariate logistic regression, adjusting for gender, age, and diagnosis. We corrected for multiple testings using false discovery rate method. Results After excluding subjects with missing covariates, there were a total of 464 subjects with 162 (35%) in the SP+ and 302 (65%) in the SP- groups. No differences were observed in gender, age or diagnosis distribution between the two SP groups. Nominal associations with p-value The 20 markers were tested again for depression in 9862 individuals from Taiwan biobank. Although none of them showed genome-wide significance, 6 SNPs had nominal p-values Discussion We found that NF1A gene maybe a susceptible gene for depression and modifiable gene for SP. Some genetic variants in this gene are related to both seasonal pattern of depressive episodes and depression with nominal significance, indicating partially shared genetic components between the development of mood symptoms and seasonality in depression. Further investigation is needed for replication with more stringent seasonal pattern evaluation, and for exploring the exact biological functions of the identified genetic variants.

Why do trauma survivors become depressed? Testing the behavioral model of depression in a nationally representative sample

Despite accumulated evidence linking trauma exposure to major depressive disorder (MDD), there is limited understanding as to why some trauma survivors subsequently develop MDD. The behavioral model of depression points to a negative reinforcement cycle of trauma-related avoidance and depressed mood, but no study has evaluated this framework in trauma survivors. This study tested the hypothesis that traumatic stress symptom-related interference with daily activities and with relationships and self-medicating traumatic stress symptoms with alcohol and with drugs would predict MDD onset in a nationally representative sample after controlling for established risk factors. Data were drawn from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) using two samples: adults reporting lifetime trauma exposure but no history of MDD at Wave 1 (n = 8301) and a subset of those participants who met criteria for lifetime PTSD prior to Wave 1 (n = 1055). Younger age, female gender, a greater number of different trauma types, traumatic stress-related interference with daily activities, and self-medicating traumatic stress symptoms with alcohol significantly predicted MDD onset in both groups. Findings underscore the role of traumatic stress-related interference and self-medication in the development of MDD.

Study Design and Rationale for the Mood and Methylation Study: A Platform for Multi-Omics Investigation of Depression in Twins.

Major depression is a complex disorder with no single, direct causal mechanism. Morbidity has been linked to genetic processes, developmental history, and unique environmental exposures. Epigenetic mechanisms, especially DNA methylation, are also likely important factors in the pathogenesis of major depressive disorder (MDD). A community-based twin sample has many advantages for epigenetic studies, given the shared genetic and developmental histories of same-sex twin pairs. This article describes the rationale and study design for the Mood and Methylation Study in which 133 twin pairs (101 monozygotic and 32 dizygotic), both discordant and concordant for lifetime history of MDD, were evaluated on a large number of variables related to MDD. The twins also provided blood samples for an epigenome-wide association study of differentially methylated regions (DMR) relevant to MDD. Although MDD is typically considered a disorder of the central nervous system, it is unfeasible to obtain a large sample of brain tissues. However, epigenetic variation is not limited to the affected tissue but can also be detected in peripheral blood leukocytes. Thus, this study focused on monocytes for the major analyses. Additional plans for the study include gene expression analysis from the same set of twins using RNA-seq and validation of significant DMRs in postmortem brain tissues from a separate sample. Moreover, sufficient samples have been collected to perform future 'multi-omic' analyses, including metabolome, microbiome, and transcriptome. Our long-term goal is to understand how epigenomic and other 'omic' factors can be manipulated for diagnostic, preventive, and therapeutic purposes for MDD and its related conditions.

History of major depression is associated with neuropsychiatric symptoms but not systemic inflammation in a cross-sectional study in obese patients

Obesity is a major public health burden associated with neuropsychiatric comorbidities leading to social and occupational impairment. Given the growing prevalence of both obesity and mental disorders worldwide, understanding the risk factors of obesity-related neuropsychiatric comorbidities is crucial to develop preventive strategies and individualized treatments. Recent findings suggest that adiposity-driven inflammation contributes to neuropsychiatric comorbidities in obesity. However, not all obese subjects afflicted with chronic inflammation develop neuropsychiatric symptoms, suggesting additional risk factors. The aim of this study was to investigate the impact of personal history of major depressive disorder (MDD) on obesity-related inflammation and neuropsychiatric symptoms, and their relationship.A case-control study was conducted comparing 66 obese patients (body mass index > 35 kg/m2) and 22 healthy non-obese participants, free of any current neuropsychiatric diseases including MDD. Neuropsychiatric symptoms were assessed using the Neurotoxicity Rating Scale (NRS). Sociodemographic and clinical variables were gathered and blood was collected for the measurement of serum levels of high-sensitivity C-reactive protein (hs-CRP). Multiple regression analyses were performed to assess the contribution of obesity and personal history of MDD to clinical outcomes and inflammatory status in study participants.Hs-CRP levels as well as NRS scores were significantly increased in the obese group. Overall, personal history of depression accounted for increased NRS scores but no significant association was found with inflammatory status. In addition, history of depression did not significantly modulate the relationship of obesity-related inflammation with NRS scores. Interestingly, obese individuals with history of recurrent MDD (n = 13) exhibited higher scores in the cognitive and sickness symptoms dimensions of the NRS compared to obese subjects with history of one depressive episode only.Findings indicate that history of depression contributes to neuropsychiatric symptoms, but not to systemic inflammation, in obese subjects free of current depressive episode. These results provide relevant information on the risk factors that may help identify obese subjects with increased risk of neuropsychiatric comorbidity.

Can't look Away: Attention control deficits predict Rumination, depression symptoms and depressive affect in daily Life

BackgroundRumination and a reduced capacity to disengage attention as appropriate to context (attention control deficits) have each been implicated in the etiology and maintenance of depressive disorders. However, it remains unclear whether rumination is a mechanism by which attention control deficits predict depression, and whether these relations are observed outside of laboratory settings. We tested whether rumination mediates the effects of attention control deficits marked by slow disengagement from negative-valenced stimuli (sad faces) and fast disengagement from positive-valenced stimuli (happy faces) on depression symptoms and depressive affects in the daily lives of adults with various depression histories. MethodForty-six participants (n = 23 with histories of Major Depressive Disorder) completed a clinical evaluation, an eye-tracking task that indexed attention control, and a 7-day Ecological Momentary Assessment (EMA) follow-up during which Negative (NA) and Positive Affect (PA) were measured at times of peak distress that occurred in the hour preceding each EMA prompt. ResultsDelayed disengagement from sad faces predicted elevated depression and NA levels, and low PA levels, independent of depression histories. Rumination mediated the effects of delayed disengagement from sad, and rapid disengagement from happy, faces on depression and NA levels. Effects of disengagement on rumination were maintained independent of depression levels. LimitationsOur sample size limited the detection of small statistical effects, and we could not clarify temporal relationships between attention control deficits and rumination. ConclusionOur findings suggest that attention inflexibility and rumination persist independent of depressive states and should be targets of clinical intervention.

Parental Depressive Symptoms and Parenting: Associations with Children’s Coping in Families of Depressed Parents

SYNOPSISObjective. This multi-method study examined parental depressive symptoms and levels of harsh/intrusive and warm/responsive parenting as correlates of secondary control coping (acceptance, cognitive reappraisal, distraction) in children of parents with a history of depression. Design. The sample included 165 parents with a history of major depressive disorder and their 9- to 15-year-old children. Parents provided self-reports of their current depressive symptoms; videorecordings of parent–child interactions were coded to determine parenting behaviors; and children reported their use of secondary control coping strategies. Results. Harsh/intrusive parenting related to less, and warm/responsive parenting related to greater, use of secondary control coping strategies in children. Parents’ current depressive symptoms were only conditionally related to children’s use of secondary control coping strategies, such that depressive symptoms moderated the relation between warm/responsive parenting behaviors and child secondary control coping. When parental depressive symptoms were low or average, warm/responsive parenting was positively related to children’s secondary control coping. When parental depressive symptoms were high, warm/responsive parenting was not associated with children’s secondary control coping. Conclusions. The association between positive parenting behaviors and children’s coping is contingent on current levels of parents’ depressive symptoms. Efforts to enhance children’s coping skills should target both parental depressive symptoms and parenting skills.

RIGHT ATRIAL THROMBUS IN TRANSIT WITH PRESUMED MASSIVE PULMONARY EMBOLISM TREATED WITH APIXABAN

SESSION TITLE: Cardiovascular Disease 2 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Right-heart thrombi (RHT) are identified in 7-18% of patients with massive pulmonary emboli. The treatment of RHT remains the subject of debate. We present the first reported case of RHT in transit treated with a direct oral anticoagulant CASE PRESENTATION: A 63-year-old woman with a history of major depressive disorder presented with six days of dyspnea and lower extremity edema. Vital signs on presentation were notable for a blood pressure of 70/68 mmHg, heart rate of 143 beats per minute, respiratory rate of 22, and oxygen saturation of 89% on room air. Examination revealed an obese woman in mild respiratory distress. The heart was tachycardic with a gallop, the lungs were clear to auscultation, and the lower extremities were warm with 2+ edema. Bilateral lower extremity pitting edema was present. Affect was guarded.Creatinine was 2.25 mg/dL (creatinine clearance 45 ml/min). Troponin T was 0.016 ng/mL. Electrocardiogram showed sinus tachycardia.Transthoracic echocardiography revealed evidence of right ventricular pressure overload, and a large, mobile echo density within the right atrium (Fig. 1). The right ventricular systolic pressure was estimated at 52 mmHg. The patient declined all further testing, including phlebotomy. She consented to oral medications. The patient was managed with the psychiatry service. She was deemed to have capacity to decline invasive procedures. With the significant barriers to therapy, a direct-acting oral anticoagulant was felt to be best therapeutic option. ,Apixaban and oral antidepressant medications were started. On hospital day 15, she was transferred to the inpatient psychiatry unit. Apixaban was continued. On hospital day 28, repeat echocardiogram revealed improvement in right ventricular size and function, and decrease in right ventricular systolic pressure to 32 mmHg. The right atrial thrombus was no longer visualized (Fig. 2). DISCUSSION: RHT-in-transit are associated with very high mortality, up to 40% even with treatment. Without treatment, they are almost uniformly fatal. A case series of 38 patients with RHT showed no statistical difference between various therapeutic options; thrombolysis, surgery and anticoagulation. Apixaban has been shown to be non-inferior to enoxaparin and warfarin for the treatment of VTE; however it has not been studied in patients with either massive PE or RHTIn this case, clinical circumstances dictated the use of a direct oral anticoagulant when other therapeutic options would otherwise have been used. The outcome in this case cannot be generalized to other patients presenting with either massive PE or RHT in the absence of further investigation CONCLUSIONS: RHT-in-transit are seen in a fraction of patients with massive PE and are associated with a high mortality despite intervention. This case illustrates satisfactory treatment of RHT-in-transit with apixaban due to limited therapeutic options Reference #1: Treatment of Right Heart Thrombi Associated. Deisy Barrios, MD,a Jeremy Chavant, MD,b David Jiménez, PhD,a Laurent Bertoletti, PhD,c Vladimir Rosa-Salazar, PhD. 5, s.l. : The American Journal of Medicine, 2017, Vol. 130 Reference #2: Oral Apixaban for the Treatment of Acute Venous Thromboembolism. Giancarlo Agnelli, Harry R. Bulle, Alexander Cohen, Madelyn Curto, Alexander S. Gallus, Margot Johnson, Urszula Masiukiewicz, Raphael Pak, John Thompson, Gary E. Raskob, and Jeffrey I. Weitz. 9, s.l. : The New England Journal of Medicine, 2013, Vol. 369. Reference #3: Outcome of patients with right heart thrombi: the Right Heart Thrombi European Registry. Marcin Koć, Maciej Kostrubiec, Waldemar Elikowski, Nicolas Meneveau, Mareike Lankeit, Stefano Grifoni, Agnieszka Kuch-Wocial, Antoniu Petris Beata Zaborska, Branislav S. Stefanović, Thomas Hugues, Adam Torbicki, Stavros Konstantinides and Piotr Pruszczyk. s.l. : European Respiratory Journal, 201 DISCLOSURES: no disclosure on file for David Ain; No relevant relationships by Omar Ayah, source=Web Response No relevant relationships by Jessica Joseph, source=Web Response No relevant relationships by Zainab Mahmoud, source=Web Response

History of childhood emotional abuse predicts lower resting-state high-frequency heart rate variability in depressed women

Childhood emotional abuse impairs emotion regulation and increases risk for major depressive disorder in adulthood. Mounting evidence suggests that decreased resting-state high-frequency heart rate variability, an index of parasympathetic function, represents a transdiagnostic biomarker of emotion dysregulation. We propose that adults with histories of major depressive disorder and childhood emotional abuse represent a subpopulation at particularly high risk to exhibit deficits in parasympathetic control. The current report compared resting-state high-frequency heart rate variability across three groups: (1) depressed women who endorsed childhood emotional abuse (N = 11); (2) depressed women without childhood emotional abuse (N = 19), and (3) never-depressed women without childhood emotional abuse (N = 22). Participants completed childhood trauma self-reports and assessment of resting-state high-frequency heart rate variability. ANCOVAs comparing the three groups after controlling for health-related, psychiatric, and respiratory factors were significant. Depressed women with childhood emotional abuse exhibited lower high-frequency heart rate variability than both groups without childhood emotional abuse (d’s ranging from 0.81—0.92). Surprisingly, psychiatric factors were non-significant predictors, indicating that childhood emotional abuse may have a unique impact on autonomic functioning. Future research on larger samples is needed to disentangle the relative and synergistic burdens of depression and childhood trauma on physiologic indicators of emotion dysregulation.