History Of Major Depressive Disorder Research Articles

The interplay of childhood maltreatment and maternal depression in relation to the reward positivity in youth.

Guided by developmental psychopathology and dual-risk frameworks, the present study examined the interplay between childhood maltreatment and maternal major depression history in relation to neural reward responsiveness in youth. The sample consisted of 96 youth (ages 9-16; M = 12.29 years, SD = 2.20; 68.8% female) drawn from a large metropolitan city. Youth were recruited based on whether their mothers had a history of major depressive disorder (MDD) and were categorized into two groups: youth with mothers with a history of MDD (high risk; HR; n = 56) and youth with mothers with no history of psychiatric disorders (low risk; LR; n = 40). The reward positivity (RewP), an event-related potential component, was utilized to measure reward responsiveness and the Childhood Trauma Questionnaire measured childhood maltreatment. We found a significant two-way interaction between childhood maltreatment and risk group in relation to RewP. Simple slope analysis revealed that in the HR group, greater childhood maltreatment was significantly associated with reduced RewP. The relationship between childhood maltreatment and RewP was not significant among the LR youth. The present findings demonstrate that the association between childhood maltreatment and blunted reward responsiveness is dependent on whether offspring have mothers with histories of MDD.

Gene expression profiling in peripheral blood lymphocytes for major depression: preliminary cues from Chinese discordant sib-pair study

The etiology of major depressive disorder (MDD) involves many factors such as heredity and environment. There are very few MDD-related studies in Chinese population using twin or sib-pairs for depression-control samples. Here we used the microarray approach and compared gene expression profiling of peripheral blood lymphocytes from 6 sib-pairs discordant on lifetime history of MDD. Within sib-pair differentially expressed genes are obvious fewer in the 1st, 2nd, and 5th compared with those in the 3rd, 4th, and 6th sib-pairs. Gene expression pattern of these DEGs distinguished MDD individuals from the normal one in 3rd, 4th, and 6th sib-pair but not in the 1st, 2nd, and 5th pair, suggesting heterogeneity of different sib-pairs and somewhat commonalities among the 3rd, 4th, and 6th sib-pairs. Comprehensive protein interaction network analysis revealed two key genes PTH and FGF2 in a dominant network where the majority of the genes were significantly down-regulated. PTH was significantly down-regulated in all the sib-pairs while FGF2 was in the 3rd, 4th, and 6th sib-pairs. KEGG enrichment analysis of all the DEGs in networks showed that PTH and related genes were significantly enriched in the pathway of parathyroid hormone secretion, synthesis, and action while FGF2 and related genes were significantly enriched in the pathways of cancer and specifically breast cancer. Generally reduced expression of these genes in peripheral blood lymphocytes of MDD individuals implied their functional repression associated with MDD. Pending validation in more samples, the findings in this study provided valuable cues for understanding the potential mechanism of MDD, as well as potential markers for the diagnosis and treatment of depression in the Chinese population.

Maternal suicidality interacts with blunted reward processing to prospectively predict increases in depressive symptoms in 8-to-14-year-old girls

Both a hypoactive reward system and maternal depression are associated with the onset of Major Depressive Disorder (MDD) in youth. Recent research indicates that blunted reward processing and maternal history of depression may interact to predict increases in depressive symptoms, however, the role of specific maternal depressive symptoms has not been examined. The current study investigated whether maternal depressive symptoms, history of MDD, and suicidal thoughts and/or behaviors (STBs) might lead to prospective increases in depressive symptoms one year later in the context of hypoactive reward processing. In a sample (N = 212) of 8 to 14-year-old girls, we assessed depressive symptoms in youth at baseline and follow up, while reward processing was measured using the Reward Positivity (RewP) event-related brain potential. Maternal STBs, current depressive symptoms, and history of maternal MDD were assessed at baseline. The results indicated that only girls with a blunted RewP and maternal STBs exhibited increased depressive symptoms one year later. These results were not evident when maternal depressive symptoms or maternal history of MDD was examined as the moderator. Overall, the current study provides evidence that maternal STBs uniquely impact youth with blunted reward processing.

Anhedonic Depression Is Not Associated With Risk of Recurrent Major Adverse Cardiac Events and All-Cause Mortality in Acute Coronary Syndrome Patients.

Depression after acute coronary syndrome (ACS) is common and increases risks of adverse outcomes, but it remains unclear which depression features are most associated with major adverse cardiac events (MACE) and all-cause mortality (ACM). To examine whether a subtype of depression characterized by anhedonia and major depressive disorder (MDD) predicts 1-year MACE/ACM occurrence in ACS patients compared to no MDD history. We also consider other depression features in the literature as predictors. Patients (N = 1,087) presenting to a hospital with ACS completed a self-report measure of current depressive symptoms in-hospital and a diagnostic interview assessing MDD within 1 week post-hospitalization. MACE/ACM events were assessed at 1-, 6-, and 12-month follow-ups. Cox regression models were used to examine the association of the anhedonic depression subtype and MDD without anhedonia with time to MACE/ACM, adjusting for sociodemographic and clinical covariates. There were 142 MACE/ACM events over the 12-month follow-up. The 1-year MACE/ACM in patients with anhedonic depression, compared to those with no MDD, was somewhat higher in an age-adjusted model (hazard ratio [HR] = 1.63, p = .08), but was not significant after further covariate adjustment (HR = 1.24, p = .47). Of the additional depression features, moderate-to-severe self-reported depressive symptoms significantly predicted the risk of MACE/ACM, even in covariate-adjusted models (HR = 1.72, p = .04), but the continuous measure of self-reported depressive symptoms did not. The anhedonic depression subtype did not uniquely predict MACE/ACM as hypothesized. Moderate-to-severe levels of total self-reported depressive symptoms, however, may be associated with increased MACE/ACM risk, even after accounting for potential sociodemographic and clinical confounders.

Increased maternal inflammation and poorer infant neurobehavioural competencies in women with a history of major depressive disorder from the psychiatry research and motherhood – Depression (PRAM-D) study

IntroductionStress in pregnancy is associated with adverse outcomes in offspring, and developmental programming is a potential mechanism. We have previously shown that depression in pregnancy is a valid and clearly defined stress paradigm, and both maternal antenatal and offspring stress-related biology is affected. This study aims to clarify whether maternal biology in pregnancy and offspring outcomes can also be influenced by a history of a prior depression, in the absence of depression in pregnancy. Our primary hypothesis is that, similarly to women with depression in pregnancy, women with a history of depression but who are not depressed in pregnancy will have increased cortisol secretion and markers of immune system function, and that their offspring will have poorer neuro-developmental competencies and increased cortisol stress response. MethodsA prospective longitudinal design was used in 59 healthy controls and 25 women with a past history of depression who were not depressed in pregnancy, named as ‘history-only’, and their offspring. Maternal antenatal stress-related biology (cortisol and markers of immune system function) and offspring outcomes (gestational age at birth, neonatal neurobehaviour (Neonatal Behavioural Assessment Scale, NBAS), cortisol stress response and basal cortisol at 2 and 12 months) and cognitive, language and motor development (Bayley Scales of Infant and Toddler Development (BSID)) were measured. ResultsCompared with healthy pregnant women, those with a history of depression who remain free of depression in pregnancy exhibit increased markers of immune system function in pregnancy: IL-8 (d = 0.63, p = 0.030), VEGF (d = 0.40, p = 0.008) and MCP-1 (d = 0.61, p = 0.002) and have neonates with lower neurobehavioural scores in most areas, reaching statistical significance in thesocial-interactive (d = 1.26, p = 0.015) cluster. However, there were no differences in maternal or offspring HPA axis function or in infant development at 12 months. ConclusionOur study indicates that pregnant women with a history of depression have increased markers of immune system function, and their offspring show behavioural alterations that may be the effects of in utero programming, epigenetic factors or genetic predisposition.

An assessment of factors associated with neurocognitive decline in people living with HIV.

Despite the widespread use of combination antiretroviral therapy (cART), HIV-associated neurocognitive impairment (NCI) remains a health concern. However, limited research has been done to identify factors associated with neurocognitive decline. We assessed risk factors associated with neurocognitive decline in people living with HIV using a definition of decline that is statistically easy to adopt, is based on a commonly used neuropsychological cut-off and may be clinically relevant. Cox proportional hazards modeling was performed using the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study database. 581 participants were followed for up to 12years. Neurocognitive decline was defined as the first observed drop in global T-scores of at least 2.67. Lifetime methamphetamine use had the strongest association with neurocognitive decline (adjusted Hazard Ratio; aHR = 1.48; 95% CI = 0.92-2.39) followed by no current antiretroviral medication use (aHR = 1.32; 95% CI = 0.91-1.92). Other risk factors included Hispanic ethnicity, lifetime history of major depressive disorder, lifetime cannabis use, hepatitis-C infection, and difficulty eating, dressing, bathing, or using the toilet. Results indicate that consistent use of ART may be of high significance to preserving neurocognition. Furthermore, Hispanic patients, those with a history of depression and substance use, and those having difficulty in essential activities of daily living may require vigilant follow-up.

Factores asociados con el comportamiento suicida en adolescentes. Estudio poblacional

IntroductionSuicide is the third leading cause of death in young people between 15 and 19 years old, a population in which it has been increasing since 2014. Determining the factors associated with this complex behaviour is the first step in developing early intervention strategies. The objective was to analyse the sociodemographic and clinical psychiatric factors associated with suicidal behaviour in adolescents from Envigado, in 2017. MethodsCross-sectional, population-based analytical study, nested in the Envigado Population-based Mental Health Study, 2017. Two hundred and one adolescents aged 15 to 18 were included, to whom the CIDI-3 was applied. The prevalence of suicidal behaviour was calculated and associated sociodemographic and clinical factors were analysed using multivariate logistic regression. ORs with 95% CIs are presented. ResultsThe mean age was 15 years, 51.7% were women. The prevalences of suicidal behaviour were 20.9% for ideation, 12.9% for planning and 10.9% for attempt. Being a woman (OR=1.12; 95% CI, 1.02-4.87), of low socioeconomic status (OR=4.09; 95% CI, 1.80-9.23), with a history of oppositional defiant disorder (OR=4.89; 95% CI, 1.17-20.39) or a history of major depressive disorder (OR=5.26; 95% CI, 1.91-14.48) were associated with suicidal behaviour. ConclusionsAmong adolescents in the city of Envigado, suicidal behaviour has a high prevalence, being higher among those who are socially and economically disadvantaged, particularly among women. This profile should be considered when planning strategies to promote mental health and prevent mental disorders.

Investigating the impact of COVID-19 lockdown on adults with a recent history of recurrent major depressive disorder: a multi-Centre study using remote measurement technology

BackgroundThe outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes a clinical illness Covid-19, has had a major impact on mental health globally. Those diagnosed with major depressive disorder (MDD) may be negatively impacted by the global pandemic due to social isolation, feelings of loneliness or lack of access to care. This study seeks to assess the impact of the 1st lockdown – pre-, during and post – in adults with a recent history of MDD across multiple centres.MethodsThis study is a secondary analysis of an on-going cohort study, RADAR-MDD project, a multi-centre study examining the use of remote measurement technology (RMT) in monitoring MDD. Self-reported questionnaire and passive data streams were analysed from participants who had joined the project prior to 1st December 2019 and had completed Patient Health and Self-esteem Questionnaires during the pandemic (n = 252). We used mixed models for repeated measures to estimate trajectories of depressive symptoms, self-esteem, and sleep duration.ResultsIn our sample of 252 participants, 48% (n = 121) had clinically relevant depressive symptoms shortly before the pandemic. For the sample as a whole, we found no evidence that depressive symptoms or self-esteem changed between pre-, during- and post-lockdown. However, we found evidence that mean sleep duration (in minutes) decreased significantly between during- and post- lockdown (− 12.16; 95% CI − 18.39 to − 5.92; p < 0.001). We also found that those experiencing clinically relevant depressive symptoms shortly before the pandemic showed a decrease in depressive symptoms, self-esteem and sleep duration between pre- and during- lockdown (interaction p = 0.047, p = 0.045 and p < 0.001, respectively) as compared to those who were not.ConclusionsWe identified changes in depressive symptoms and sleep duration over the course of lockdown, some of which varied according to whether participants were experiencing clinically relevant depressive symptoms shortly prior to the pandemic. However, the results of this study suggest that those with MDD do not experience a significant worsening in symptoms during the first months of the Covid − 19 pandemic.

Injuries in Left Corticospinal Tracts, Forceps Major, and Left Superior Longitudinal Fasciculus (Temporal) as the Quality Indicators for Major Depressive Disorder.

At present, the etiology and pathogenesis of major depressive disorder (MDD) are still not clear. Studies have found that the risk of first-degree relatives of MDD is 2–3 times that of the general population. Diffusion tensor imaging (DTI) has been previously used to explore the pathogenesis of MDD. The purpose of this study is to explore the etiology of MDD by DTI and further to explore the correlation between its clinical characteristics and the structural changes of white matter in the brain. The study included 27 first-episode, drug-naive patients with MDD, 16 first-degree relatives without MDD, and 28 healthy control subjects with no family history of MDD (HC). Results showed that the fractional anisotropy (FA) differences among the three groups were mainly in the left anterior thalamic radiation (LATR), right anterior thalamic radiation (RATR), left corticospinal tracts (LCST), forceps major (FMa), right inferior longitudinal fasciculus (RILF), and left superior longitudinal fasciculus (temporal) (LSLF(T)). Among the 6 sites, LCST, FMa, and LSLF(T) showed significant differences between MDD and First-degree relatives compared to HC. MDD patients had significant emotional symptoms, somatic symptoms, and cognitive impairment. FMa FA was significantly positively correlated with delayed memory score (r = 0.43, P = 0.031), and RILF FA was significantly negatively correlated with the FSS score (r = −0.42, P = 0.028). These results revealed that the white matter characteristics of MDD-susceptible patients were LCST, FMa, and LSLF(T) lesions, all of which may be quality indicators of MDD.

Oral contraceptives, depressive and insomnia symptoms in adult women with and without depression

BackgroundWorldwide, oral contraceptive (OC) use is a very common form of birth control, although it has been associated with symptoms of depression and insomnia. Insomnia is a risk factor for major depressive disorder (MDD) but may also be a symptom of the disorder. Despite the large number of women who use OC, it is yet unknown whether women with previous or current diagnosis of depression are more likely to experience more severe depressive and insomnia symptoms during concurrent OC use than women without diagnosis of depression. AimThis study examined associations between OC use and concurrent symptoms of depression (including atypical depression) and insomnia as well as between OC and prevalences of concurrent dysthymia and MDD. Participants were adult women with and without a history of MDD or dysthymia. We hypothesized that OC use is associated with concurrent increased severity of depressive symptoms and insomnia symptoms, as well as with an increased prevalence of concurrent diagnoses of dysthymia and MDD. We also hypothesized that a history of MDD or dysthymia moderates the relationship between OC use and depressive and insomnia symptoms. MethodsMeasurements from premenopausal adult women from the Netherlands Study of Depression and Anxiety (NESDA) were grouped, based on whether participants were using OC or naturally cycling (NC). OC use, timing and regularity of the menstrual cycle were assessed with a structured interview, self-reported symptoms of depression (including atypical depression), insomnia with validated questionnaires, and MDD and dysthymia with structured diagnostic interviews. ResultsWe included a total of 1301 measurements in women who reported OC use and 1913 measurements in NC women (mean age 35.6, 49.8% and 28.9% of measurements in women with a previous depression or current depression, respectively). Linear mixed models showed that overall, OC use was neither associated with more severe depressive symptoms (including atypical depressive symptoms), nor with higher prevalence of diagnoses of MDD or dysthymia. However, by disentangling the amalgamated overall effect, within-person estimates indicated increased depressive symptoms and depressive disorder prevalence during OC use, whereas between-person estimated indicated lower depressive symptoms and prevalence of depressive disorders. OC use was consistently associated with more severe concurrent insomnia symptoms, in the overall estimates as well as in the within-person and between-person estimates. Presence of current or previous MDD or dysthymia did not moderate the associations between OC use and depressive or insomnia symptoms. DiscussionThe study findings showed consistent associations between OC use and more severe insomnia symptoms, but no consistent associations between OC and depressive symptoms or diagnoses. Instead, post-hoc analyses showed that associations between OC and depression differed between within- and between person-estimates. This indicates that, although OC shows no associations on the overall level, some individuals might experience OC-associated mood symptoms. Our findings underscore the importance of accounting for individual differences in experiences during OC use. Furthermore, it raises new questions about mechanisms underlying associations between OC, depression and insomnia.

Polygenic risk for major depression is associated with lifetime suicide attempt in US soldiers independent of personal and parental history of major depression.

Suicide is a major public health problem. The contribution of common genetic variants for major depressive disorder (MDD) independent of personal and parental history of MDD has not been established. Polygenic risk score (using PRS-CS) for MDD was calculated for US Army soldiers of European ancestry. Associations between polygenic risk for MDD and lifetime suicide attempt (SA) were tested in models that also included parental or personal history of MDD. Models were adjusted for age, sex, tranche (where applicable), and 10 principal components reflecting ancestry. In the first cohort, 417 (6.3%) of 6,573 soldiers reported a lifetime history of SA. In a multivariable model that included personal [OR=3.83, 95% CI:3.09-4.75] and parental history of MDD [OR=1.43, 95% CI:1.13-1.82 for one parent and OR=1.64, 95% CI:1.20-2.26 for both parents), MDD PRS was significantly associated with SA (OR=1.22 [95% CI:1.10-1.36]). In the second cohort, 204 (4.2%) of 4,900 soldiers reported a lifetime history of SA. In a multivariable model that included personal [OR=3.82, 95% CI:2.77-5.26] and parental history of MDD [OR=1.42, 95% CI:0.996-2.03 for one parent and OR=2.21, 95% CI:1.33-3.69 for both parents) MDD PRS continued to be associated (at p=.0601) with SA (OR=1.15 [95% CI:0.994-1.33]). A soldier's PRS for MDD conveys information about likelihood of a lifetime SA beyond that conveyed by two predictors readily obtainable by interview: personal or parental history of MDD. Results remain to be extended to prospective prediction of incident SA. These findings portend a role for PRS in risk stratification for suicide attempts.

Gender differences in the associations of multiple psychiatric and chronic conditions with major depressive disorder among patients with opioid use disorder

Purpose The study examined the associations of multiple psychiatric and chronic conditions with the self-reported history of major depressive disorder (MDD) among patients with opioid use disorder (OUD) and tested whether the associations differed by gender. Methods We conducted a secondary data analysis of baseline data from a clinical trial including 1,646 participants with OUD, of which 465 had MDD. A variable cluster analysis was used to classify chronic medical and psychiatric conditions. Multivariable logistic regression analyses were used to estimate their associations with MDD in subjects with OUD. Results Nine variables were divided into three clusters: cluster 1 included heart condition, hypertension, and liver problems; cluster 2 included gastrointestinal (GI) problems and head injury, and cluster 3 included anxiety disorder, bipolar disorder, and schizophrenia. The overall prevalence of MDD in participants with OUD was 28.3% (22.8% for males and 39.5% for females). Gender, anxiety disorder, schizophrenia, liver problems, heart condition, GI problems, and head injury were significantly associated with MDD. Gender-stratified analyses showed that bipolar disorder, liver problems and individuals with one chronic condition were associated with MDD only in males, whereas heart condition, hypertension, and GI problems were associated with MDD only in females. In addition, anxiety disorder, head injury, individuals with one or more than two psychiatric conditions, and individuals with more than two chronic conditions were associated with MDD regardless of gender. Conclusions Treatment plans in patients with OUD should not only address MDD but also co-morbid psychiatric and chronic medical conditions that occur with MDD.

Enduring problems in the offspring of depressed parents followed up to 38 years.

Backgroundwhile the increased risk of major depressive disorder (MDD) in offspring of depressed parents is one of the best-replicated findings in psychiatry, their long-term outcomes are less well known. The clinical outcomes of biological offspring of depressed (high-risk) and not depressed (low-risk) parents who have been directly interviewed over the years are presented.Methodsa longitudinal retrospective cohort study began in 1982, and 276 biological offspring of moderately-to-severely depressed or non-depressed parents from the same community were followed up to 38 years. Rates of psychiatric disorders for offspring were collected by clinically trained interviewers. Final diagnoses were made by M.D. or Ph.D. clinicians. Mortality and cause of death were obtained from relatives and registries.Findingshigh- compared to low-risk offspring continue to have about a three-fold increased risk of MDD, increased rates of anxiety disorder, substance dependence, and poorer functioning over the life course. Adolescence and early adulthood remain prime age of first onsets. Within high-risk group only, the death rate due to unnatural causes, suicides and overdose was 4·97/100 in the offspring and 5·36/100 in their parents. This subsample of White, lower-educated, often unemployed persons, who died by unnatural causes are similar demographically to those described as having a recent increase in ‘deaths of despair’.Interpretationfamily history of MDD continues to be a powerful predictor of clinical course and mortality and should be probed in clinical visits, especially in youth when depression usually first appears.

Association between adolescent oral contraceptive use and future major depressive disorder: aprospective cohort study.

BackgroundBecause of the widespread use of oral contraceptives (OCs) and the devastating effects of depression both on an individual and a societal level, it is crucial to understand the nature of the previously reported relationship between OC use and depression risk. Insight into the impact of analytical choices on the association is important when interpreting available evidence. Hence, we examined the association between adolescent OC use and subsequent depression risk in early adulthood analyzing all theoretically justifiable models.MethodsData from the prospective cohort study TRacking Adolescents’ Individual Lives Survey, among women aged 13–25 years were used. Adolescent OC use (ages 16–19 years) was used as a predictor and major depressive disorder (MDD) in early adulthood (ages 20–25 years), as assessed by the Diagnostic and Statistical Manual of Mental Disorders‐IV oriented Lifetime Depression Assessment Self‐Report and the Composite International Diagnostic Interview, was used as an outcome. A total of 818 analytical models were analyzed using Specification Curve Analysis in 534 adolescent OC users and 191 nonusers.ResultsOverall, there was an association of adolescent OC use and an episode of MDD in early adulthood [median odds ratio (OR)median = 1.41; ORmin = 1.08; ORmax = 2.18, p < .001], which was driven by the group of young women with no history of MDD (ORmedian = 1.72; ORmin = 1.21; ORmax = 2.18, p < .001).ConclusionsIn summary, adolescent OC use was associated with a small but robust increased risk for experiencing an episode of MDD, especially among women with no history of MDD in adolescence. Understanding the potential side effects of OCs will help women and their doctors to make informed choices when deciding among possible methods of birth control.

Severity of substance use as an indicator of suicide risk among U.S. military veterans

BackgroundSubstance use is a strong risk factor for suicidal behavior. To date, however, no known study has evaluated optimal cut-off scores on substance use severity measures to identify individuals who may be at elevated risk for suicide. MethodsData were analyzed from the 2019–2020 National Health and Resilience in Veterans Study, which surveyed a nationally representative sample of 4069 U.S. veterans. Receiver operating characteristic curve analyses were conducted to identify cut-off scores on the Alcohol Use Disorders Identification Test (AUDIT) and Screen of Drug Use (SDU) that optimally differentiated veterans with and without past-year suicidal ideation (SI) in the full sample, as well a high-risk subsample with histories of major depressive disorder (MDD) and/or posttraumatic stress disorder (PTSD). ResultsThe prevalence of past-year SI was 11.7% (n = 387); A total of 10.5% (n = 360) of the sample screened positive for past-year alcohol use disorder, 9.1% (n = 314) for past-year drug use disorder, and 22.4% (n = 833) for lifetime MDD/PTSD. The optimal AUDIT cut-off score that differentiated suicide ideators and non-ideators was ≥14 in the full sample, and ≥18 in the high-risk subsample; these scores are indicative of moderate-to-severe alcohol use disorder. The optimal SDU cut-off score was ≥1 for both the full sample and high-risk subsample, which is lower than the recommend cut-off score for probable drug use disorder (≥7). ConclusionsResults identify high-specificity thresholds on the AUDIT and SDU that may have clinical utility in suicide risk assessment in veterans. Veterans with moderate-to-severe alcohol use disorder or who use non-prescription drugs may warrant further suicide risk assessment.

Perimenopause and First-Onset Mood Disorders: A Closer Look.

Perimenopause is often a time of social, emotional, and physical change. Various factors contribute to the development of mood disorders during this time. There is a known association among women with previous history of major depressive disorder or bipolar disorder and relapse during the menopausal transition. First-onset mood disorders during this time have been less studied. A literature review in PsycInfo Ovid of records pertaining to first-onset mood disorders during perimenopause showed that this multifactorial process involves hormonal fluctuations, with estrogen being a key player. In addition, vasomotor symptoms, previous negative life events, and socioeconomic status were found to contribute to first-onset mood disorders during perimenopause. Treatment options include established medication regimens for psychiatric conditions; however, hormone therapy also has proven beneficial for this patient population. Further research, particularly on bipolar disorder, is needed to develop a clear association between perimenopause and first-onset mood disorders.

Differential effects of estradiol on neural and emotional stress response in postmenopausal women with remitted Major Depressive Disorder

BackgroundEstrogen fluctuations throughout the lifespan may contribute to major depressive disorder (MDD) risk in women through effects on brain networks important in stress responding, and mood regulation. Although there is evidence to support ovarian hormone treatment for peri-menopausal depression, postmenopausal use has not been well examined. The objective of this study was to investigate whether estrogen modulation of the neural and emotional cognitive responses to stress differs between postmenopausal women with and without MDD history. Methods60 postmenopausal women completed an fMRI psychosocial stress task, after receiving no drug or 3 months of daily estradiol (E2). fMRI activity and subjective mood response were examined. ResultsIn women without a history of MDD, E2 was associated with a more negative mood response to stress and less activity in emotional regulation regions. In women with a history of MDD, E2 was associated with a less negative mood response to stress and less activity in emotion perception regions. LimitationsThis study was limited by open-label estradiol administration and inclusion of participants using antidepressants. ConclusionsThese results support a differential effect of estrogen on emotional and neural responses to psychosocial stress in postmenopausal women with MDD history and may reflect a shift in brain activity patterns related to emotion processing following menopause.

“I Burn Myself to Get High”: A Case Report on how Pain can be an Addiction

<strong>Background:</strong> Authors have argued that engagement in Non-Suicidal Self Injurious (NSSI) involves addictive components similar to those of other behavioral or process addictions. The following elements of addiction have been accepted: (a) compulsivity, (b) loss of control (c) continued use of the substance or behavior despite adverse consequences. Authors have also discussed the role of tolerance in addictive behaviors and its connection to specific neurochemical processes, such as the endogenous opioid system (EOS). We present a case of a patient who showed addictive patterns to her NSSI. <strong>Methods:</strong> A case report, as well as a review of research and literature for Non-Suicidal Self Injury, was conducted. <strong>Result:</strong> Ms. X is a 24-year-old female with a history of Major Depressive Disorder admitted to the psychiatric unit for worsening suicidal ideation and self-injurious behavior. She was noted to have multiple tear drop burn scars on her forearms. According to her, these wounds are her way of “getting high”. She reported that she used to have severe anxiety and was using marijuana to cope. When she could not buy cannabis, she decided to burn her arm in frustration and has been burning her arms. She described the pain as “sharp and good. She expressed that the high that she experienced with the burning was “intense at first, then mellowed out and lasted long”. The patient was then stabilized on Lexapro, Vistaril, and was able to refrain from inflicting pain during her stay. The patient was discharged to outpatient addiction. The patient has not had any readmission since discharge. <strong>Conclusion: </strong>Compulsive behavior is preceded immediately by negative emotions and performed to alleviate negative emotions. Lack of control seems evident in such situations because acts of NSSI exceed the individual’s intentions or expectations. The DSM-5 diagnosis criteria of NSSI is that the individuals who self-injure continue to engage in NSSI despite adverse effects. Tolerance in self-injuring individuals’ experience of NSSI would provide an additional reason to classify NSSI as a process addiction. Endorphins contribute to the experience of analgesia and increase an individual’s sense of comfort and control or power. Engagement in NSSI may activate the EOS as a result of the experience of pain accompanying NSSI. Authors have further asserted that, as individuals who self-injure continue to activate the EOS to attain an intended result (e.g., improved mood), they may develop tolerance to the endorphins triggered by NSSI.

Clinical laboratory tests and five-year incidence of major depressive disorder: a prospective cohort study of 433,890 participants from the UK Biobank

Prevention of major depressive disorder (MDD) is a public health priority. Identifying biomarkers of underlying biological processes that contribute to MDD onset may help address this public health need. This prospective cohort study encompassed 383,131 white British participants from the UK Biobank with no prior history of MDD, with replication in 50,759 participants of other ancestries. Leveraging linked inpatient and primary care records, we computed adjusted odds ratios for 5-year MDD incidence among individuals with values below or above the 95% confidence interval (<2.5th or >97.5th percentile) on each of 57 laboratory measures. Sensitivity analyses were performed across multiple percentile thresholds and in comparison to established reference ranges. We found that indicators of liver dysfunction were associated with increased 5-year MDD incidence (even after correction for alcohol use and body mass index): elevated alanine aminotransferase (AOR = 1.35, 95% confidence interval [1.16, 1.58]), aspartate aminotransferase (AOR = 1.39 [1.19, 1.62]), and gamma glutamyltransferase (AOR = 1.52 [1.31, 1.76]) as well as low albumin (AOR = 1.28 [1.09, 1.50]). Similar observations were made with respect to endocrine dysregulation, specifically low insulin-like growth factor 1 (AOR = 1.34 [1.16, 1.55]), low testosterone among males (AOR = 1.60 [1.27, 2.00]), and elevated glycated hemoglobin (HbA1C; AOR = 1.23 [1.05, 1.43]). Markers of renal impairment (i.e. elevated cystatin C, phosphate, and urea) and indicators of anemia and macrocytosis (i.e. red blood cell enlargement) were also associated with MDD incidence. While some immune markers, like elevated white blood cell and neutrophil count, were associated with MDD (AOR = 1.23 [1.07, 1.42]), others, like elevated C-reactive protein, were not (AOR = 1.04 [0.89, 1.22]). The 30 significant associations validated as a group in the multi-ancestry replication cohort (Wilcoxon p = 0.0005), with a median AOR of 1.235. Importantly, all 30 significant associations with extreme laboratory test results were directionally consistent with an increased MDD risk. In sum, markers of liver and kidney dysfunction, growth hormone and testosterone deficiency, innate immunity, anemia, macrocytosis, and insulin resistance were associated with MDD incidence in a large community-based cohort. Our results support a contributory role of diverse biological processes to MDD onset.

Dissociating default mode network resting state markers of suicide from familial risk factors for depression.

Neural signatures of suicide risk likely reflect a combination of specific and non-specific factors, and clarifying specific factors may facilitate development of novel treatments. Previously, we demonstrated an altered pattern of resting state connectivity between the dorsal and ventral posterior cingulate cortex (d/vPCC) and the dorsal anterior cingulate cortex (dACC), as well as altered low frequency oscillations in these regions, in individuals with a history of suicidal thoughts and behaviors (STBs) compared to healthy controls. It remains uncertain, however, whether these markers were directly related to STBs or, more generally, reflect a trait-level risk factor for depression. Here, we examined data from a 3-generational longitudinal study of depression where resting state fMRI data were analyzed from 2nd and 3rd generation offspring of probands with (FH+ = 44: STB+ = 32, STB- = 12) and without (FH- = 25: STB+ = 15, STB- = 10) a family history of major depressive disorder (MDD). Standard seed-based methods and a frequency-based analysis of intrinsic neural activity (ALFF/fALFF) were employed. FH of MDD, but not a personal history of STBs or MDD, was associated with relatively reduced dPCC-dACC, and enhanced vPCC-dACC functional connectivity. FH of MDD showed a pattern of reduced ALFF in the dPCC whereas an STB history was associated with an increase. All findings were invariant to confounding by lifetime MDD and current depression severity. Overall, contrary to predictions, resting state functional connectivity within the default mode network (DMN) was associated with FH of depression rather than STBs. These findings confirm the relevance of DMN functional connectivity for mood disorders and underscore the importance of disambiguating biological factors that differentially relate to mental disorders versus STBs.