First Onset Of Major Depression Research Articles

Toward a Better Understanding of the Mechanisms and Pathophysiology of Anhedonia: Are We Ready for Translation?

Anhedonia-the loss of pleasure or lack of reactivity to pleasurable stimuli-remains a formidable treatment challenge across neuropsychiatric disorders. In major depressive disorder, anhedonia has been linked to poor disease course, worse response to psychological, pharmacological, and neurostimulation treatments, and increased suicide risk. Moreover, although some neural abnormalities linked to anhedonia normalize after successful treatment, several persist-for example, blunted activation of the ventral striatum to reward-related cues and reduced functional connectivity involving the ventral striatum. Critically, some of these abnormalities have also been identified in unaffected, never-depressed children of parents with major depressive disorder and have been found to prospectively predict the first onset of major depression. Thus, neural abnormalities linked to anhedonia may be promising targets for prevention. Despite increased appreciation of the clinical importance of anhedonia and its underlying neural mechanisms, important gaps remain. In this overview, the author first summarizes the extant knowledge about the pathophysiology of anhedonia, which may provide a road map toward novel treatment and prevention strategies, and then highlights several priorities to facilitate clinically meaningful breakthroughs. These include a need for 1) appropriately controlled clinical trials, especially those embracing an experimental therapeutics approach to probe target engagement; 2) novel preclinical models relevant to anhedonia, with stronger translational value; and 3) clinical scales that incorporate neuroscientific advances in our understanding of anhedonia. The author concludes by highlighting important future directions, emphasizing the need for an integrated, collaborative, cross-species, and multilevel approach to tackling anhedonic phenotypes.

Relationship Between Affective Temperaments and Suicide Risk in Patients With First-Onset Major Depressive Disorder.

BackgroundPeople may endorse suicidal behavior during a major depressive episode. Affective temperaments may play a role in this risk. We explored the relationship between affective temperaments and suicide and identified some traits that can predict suicide risk in depression.Materials and MethodsWe analyzed the results of the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Auto-questionnaire (TEMPS-A) in 284 participants recruited from a psychiatric clinic and the community in Beijing and compared the subscale scores (temperaments of cyclothymic, dysthymic, anxious, irritable, and hyperthymic) among major depressive disorders (MDDs) vs. the general population as well as depressive patients with vs. without suicide risk, using Student’s test, chi-square test, rank-sum test, and multivariable regression modeling.ResultsThe incidence of suicidal risk in depressive subjects was 47.62% (80/168). Being unmarried (p < 0.001), unemployed (p = 0.007), and temperaments of dysthymic, cyclothymic, anxious, and irritable scores (all p < 0.001) were significantly more prevalent in patients with depression than in the general population. Young age (p < 0.001), female sex (p = 0.037), unmarried (p = 0.001), more severe depression (p < 0.001), and dysthymic, anxious, and cyclothymic temperament (all p < 0.05) were significantly more prevalent in patients with depressive disorder than those without suicide risk. The logistic regression analysis showed that younger age (odds ratio [OR] = 0.937, 95% CI 0.905∼0.970), female sex (OR = 2.606, 95% CI 1.142∼5.948), more severe depression (OR = 1.145, 95% CI 1.063∼1.234), cyclothymic temperament (OR = 1.275, 95% CI 1.102∼1.475), and dysthymic temperament (OR = 1.265, 95% CI 1.037∼1.542) were all independently associated with high suicidal risk in patients with first-onset major depression (p < 0.05).ConclusionTemperament traits differ between the general population and people suffering from MDD. Subjects with MDD who have much more severe depressive symptoms and a cyclothymic or dysthymic temperament were at a high risk of suicide.

First-onset major depression during the COVID-19 pandemic: A predictive machine learning model

BackgroundThis study longitudinally evaluated first-onset major depression rates during the pandemic in Italian adults without any current clinician-diagnosed psychiatric disorder and created a predictive machine learning model (MLM) to evaluate subsequent independent samples. MethodsAn online, self-reported survey was released during two pandemic periods (May to June and September to October 2020). Provisional diagnoses of major depressive disorder (PMDD) were determined using a diagnostic algorithm based on the DSM criteria of the Patient Health Questionnaire-9 to maximize specificity. Gradient-boosted decision trees and the SHapley Additive exPlanations technique created the MLM and estimated each variable's predictive contribution. ResultsThere were 3532 participants in the study. The final sample included 633 participants in the first wave (FW) survey and 290 in the second (SW). First-onset PMDD was found in 7.4% of FW participants and 7.2% of the SW. The final MLM, trained on the FW, displayed a sensitivity of 76.5% and a specificity of 77.8% when tested on the SW. The main factors identified in the MLM were low resilience, being an undergraduate student, being stressed by pandemic-related conditions, and low satisfaction with usual sleep before the pandemic and support from relatives. Current smoking and taking medication for medical conditions also contributed, albeit to a lesser extent. LimitationsSmall sample size; self-report assessment; data covering 2020 only. ConclusionsRates of first-onset PMDD among Italians during the first phases of the pandemic were considerable. Our MLM displayed a good predictive performance, suggesting potential goals for depression-preventive interventions during public health crises.

INFLEXIBLE COGNITION PREDICTS FIRST ONSET OF MAJOR DEPRESSIVE EPISODES IN ADOLESCENCE.

Major depressive disorder often is characterized by a lack of cognitive and emotional flexibility, resulting in an impaired ability to adapt to situational demands. Adolescence is an important period of risk for the first onset of depression, yet relatively little is known about whether aspects of inflexibility, such as rumination and deficits in attentional shifting, could confer risk for the development of the disorder during this time. In the present study, a sample of 285 never-depressed adolescents completed self-report and behavioral measures of rumination and attentional shifting at a baseline visit, followed by up to 4 years of annual prospective follow-up diagnostic assessments. Survival analyses indicated that adolescents with greater levels of rumination or poorer attentional shifting experienced a shorter time until the first onset of major depressive episodes, even after accounting for baseline symptoms and demographic characteristics. Although girls were twice as likely as boys to experience the first onset of depression, rumination predicted a shorter time until depression onset only for boys. Rumination and attentional shifting were not correlated and predicted time until onset of major depression independently of one another. These results provide evidence that components of cognition that are characterized by rigidity and perseveration confer risk for the first onset of major depression during adolescence. Evaluating rumination and attentional shifting in adolescence may be useful in identifying individuals who are at risk for depression and who may benefit from interventions that target or alter the development of these characteristics.

Cortical thickness predicts the first onset of major depression in adolescence

Given the increasing prevalence of Major Depressive Disorder and recent advances in preventative treatments for this disorder, an important challenge in pediatric neuroimaging is the early identification of individuals at risk for depression. We examined whether machine learning can be used to predict the onset of depression at the individual level. Thirty-three never-disordered adolescents (10–15 years old) underwent structural MRI. Participants were followed for 5 years to monitor the emergence of clinically significant depressive symptoms. We used support vector machines (SVMs) to test whether baseline cortical thickness could reliably distinguish adolescents who develop depression from adolescents who remained free of any Axis I disorder. Accuracies from subsampled cross-validated classification were used to assess classifier performance. Baseline cortical thickness correctly predicted the future onset of depression with an overall accuracy of 70% (69% sensitivity, 70% specificity; p=0.021). Examination of SVM feature weights indicated that the right medial orbitofrontal, right precentral, left anterior cingulate, and bilateral insular cortex contributed most strongly to this classification. These findings indicate that cortical gray matter structure can predict the subsequent onset of depression. An important direction for future research is to elucidate mechanisms by which these anomalies in gray matter structure increase risk for developing this disorder.

Stress sensitivity interacts with depression history to predict depressive symptoms among youth: prospective changes following first depression onset.

Predictors of depressive symptoms may differ before and after the first onset of major depression due to stress sensitization. Dependent stressors, or those to which characteristics of individuals contribute, have been shown to predict depressive symptoms in youth. The current study sought to clarify how stressors' roles may differ before and after the first depressive episode. Adolescents (N = 382, aged 11 to 15 at baseline) were assessed at baseline and every 3 months over the course of 2 years with measures of stressors and depressive symptoms. Semi-structured interviews were conducted every 6 months to assess for clinically significant depressive episodes. Hierarchical linear modeling showed a significant interaction between history of depression and idiographic fluctuations in dependent stressors to predict prospective elevations of symptoms, such that dependent stressors were more predictive of depressive symptoms after onset of disorder. Independent stressors predicted symptoms, but the strength of the association did not vary by depression history. These results suggest a synthesis of dependent stress and stress sensitization processes that might maintain inter-episode depressive symptoms among youth with a history of clinical depression.

A prediction algorithm for first onset of major depression in the general population: development and validation

ObjectivePrediction algorithms are useful for making clinical decisions and for population health planning. However, such prediction algorithms for first onset of major depression do not exist. The objective of this...

Treatment-resistant residual insomnia in patients with recurrent major depressive episodes

Residual symptoms are common in depression, and their presence is associated with poorer clinical outcomes of depression. We conducted a case series study of first-onset major depression to elucidate the clinical course of residual insomnia and examine the relationship between residual insomnia and recurrence of depression. Subjects were 128 patients (57 males; mean age 52.8 years) with first-onset major depression. For all patients, we continuously assessed the number and breakdown of residual symptoms listed on the 17-item Hamilton Rating Scale for Depression and quantities of prescribed psychotropic medications during the depressive and remission phases. Even during the first remission phase, 85.9% of the patients with first-onset major depression experienced an average of 2.95 residual symptoms. The most common residual symptom was insomnia (65.4%), followed by reduced work and interests (43.3%) and fatigue (39.4%). Each additional recurrence resulted in a significantly shorter remission phase as well as significant increases in antidepressant and hypnotics dosages. Hypnotics dosage during the first remission phase for patients with three or more recurrent episodes was significantly higher than that for those with only a single episode. Our findings suggest a possible link between treatment-resistant residual insomnia during the first remission phase and recurrence risk of depression. In particular, it is possible that presence of treatment-resistant insomnia during the first remission phase is related to later recurrence of depressive episodes. It is important to see patients with treatment-resistant insomnia of early stage carefully, with special attention to treatment adherence.

Sex, stressful life events, and adult onset depression and alcohol dependence: Are men and women equally vulnerable?

Higher rates of major depression (MD) among females, and of alcohol dependence (AD) among males, are among the most routinely reported findings in psychiatric epidemiology. One of the most often pursued explanations for sex differences in both disorders suggests that males and females have a differential vulnerability to stressors, which is manifested in sex-specific ways (MD for females, AD for males). However, existing evidence in support of this explanation is mixed. In the present study, we investigated sex differences in the association between stressful life events and MD and AD in a large national sample of adults in the United States (n = 32,744) using a prospective design. Logistic regression was used to estimate associations between stressful life events and both MD and AD; sex-specific effects of stress on MD and AD were evaluated by testing interaction terms between sex and stressors in the prediction of both outcomes. The number of stressful life events was predictive of first onset MD and AD. This was true for both males and females, and sex-by-stress interaction terms did not support the hypothesis that sex-specific responses to stressful life events lead to sex differences in first onset of MD and AD among adults. These results indicate the resistance of sex differences in MD and AD to simple explanations, and suggest the need for more nuanced models that incorporate both physiological and social aspects of vulnerability.

Structural brain difference between first-onset and recurrent major depression:an MRI study

Objective By diffusion tensor imaging (DTI) and three dimensional structure MRI (3D),the brain concentration and white matter fiber difference between first-onset and recurrent major depression was explored.Methods 40 patients (first depressive episode 20 cases,recurrent major depression 20 cases) metted with CCMD-3 criteria for major depression disorder and 20 age-,gender-,education-matched healthy controls were scanned DTI and 3D.Voxel-based methods were used to analyze the imaging data in whole brain.Results Compared with the first-onset patients,recurrent patients showed reduced fractional anisotropy (FA) in the right medial frontal gyrus,the left middle temporal gyrus and the left insula ( P 30).No differences were found in white matter volume (WMV),but reduced gray matter volume (GMV) was found in the right hippocampus in recurrent patients ( P 30).Conclusion Recurrent major depressive patients exsit more white matter abnormalities than first episode patients,but has not involves WMV changes,GMV showes some atrophy. Key words: Depression; Brain sturcture; Brain white matter; Neuroimaging

Patterns of Adolescent Depression to Age 20: The Role of Maternal Depression and Youth Interpersonal Dysfunction

Considerable research has focused on youth depression, but further information is needed to characterize different patterns of onset and recurrence during adolescence. Four outcome groups by age 20 were defined (early onset-recurrent, early-onset-desisting, later-onset, never depressed) and compared on three variables predictive of youth depression: gender, maternal depression, and interpersonal functioning. Further, it was hypothesized that the association between maternal depression and youth depression between 15 and 20 is mediated by early-onset depression and interpersonal dysfunction by age 15. Eight hundred sixteen community youth selected for depression risk by history (or absence) of maternal depression were interviewed at age 15, and 699 were included in the 5-year follow-up. Controlling for gender, early onset and interpersonal dysfunction mediated the link between maternal depression and late adolescent major depression. Different patterns for males and females were observed. For males maternal depression's effect was mediated by early onset but not interpersonal difficulties, while for females maternal depression's effect was mediated by interpersonal difficulties but not early onset. Maternal depression did not predict first onset of major depression after age 15. The results suggest the need for targeting the impact of maternal depression's gender-specific effects on early youth outcomes, and also highlight the different patterns of major depression in youth and their likely implications for future course of depression.

Three-Year Incidence of First-Onset Depressive Syndrome in a Population Sample of Older Adults: The Cache County Study

Estimates of incidence of late-life depression vary greatly with few studies excluding demented cases through in-depth evaluation and most studies failing to control for the effect of mortality and interval treatment. In a large population-based study, the authors examined the effect on incidence of first-onset depressive syndrome to determine whether any gender or age differences in incidence are attenuated with inclusion of these additional measures. Incidence rates of depressive syndrome per 1,000 person-years are presented for 2,877 nondemented elderly (ages 65 to 100 years) residents of Cache County, Utah. Cases are identified by direct interview methods, by inference from prescription antidepressant medicine use, and by postmortem informant interview for decedents. In-person interviews yielded incidence rates of first-onset depressive disorder (any type) of 13.09 for men and 19.44 for women. Inclusion of antidepressant users increased these figures to 15.55 for men and 23.30 for women. Addition of postmortem interview data yielded rates of 20.66 for men and 26.29 for women. Individuals with no history of depression had rates for major depression of 7.88 for men and 8.75 for women; minor depression rates were 19.23 for men and 24.46 for women (p = 0.691; effect for minor depression p <0.0001). Age did not predict incidence. Incidence of first-onset major depression varies with data source and prior lifetime history of depression. Gender effects apparent in interview data are attenuated when postmortem information and pharmacotherapy were considered.

Factors that differentiate early vs. later onset of major depression disorder

This report explores the relationship between age of first onset of major depression and other demographic and clinical features in the first 1500 patients entering the Sequenced Treatment Alternative to Relieving Depression (STAR*D) study. Outpatients, 18–75 years of age, with nonpsychotic major depressive disorder (MDD) from either primary care or psychiatric practices constitute the population. Age of onset was defined at study intake by asking patients to estimate the age at which they experienced the onset of their first major depressive episode. This report divides the population in terms of pre-adult (before age 18) onset and adult (age 18 or later) onset. The results suggest that MDD that begins before age 18 has a distinct set of demographic (female gender) and clinical correlates (longer duration of illness; longer current episodes; more episodes; more suicidality; greater symptom severity; more psychiatric symptoms associated with Axis I comorbidity; and more sadness, irritability, agitation and atypical symptom features), and it appears associated with significant psychosocial consequences (lower educational attainment and marriage rates). Thus, pre-adulthood onset MDD is a particularly severe and chronic condition.

Bipolar disorder

The EBMH Notebook summarises key messages about bipolar disorder, sourced from: Clin Evid Concise2003;10:208–9.[OpenUrl][1] For this review, Clinical Evidence Concise searched and appraised material published until April 2002. Bipolar disorder...

Treatment of panic attack and risk of major depressive disorder in the community.

The authors' goal was to determine whether treatment of panic attacks has a protective effect on the risk of major depression in the community. Data were drawn from the National Comorbidity Survey, a community-based household sample representative of the U.S. adult population. A Cox proportional hazard model was used to estimate the association between risk of first-onset major depression and panic among subjects who had or had not received treatment for panic. A significantly smaller proportion of individuals who received treatment for panic (19%) than those who did not receive treatment (45%) developed major depression. This difference remained significant in a Cox proportional hazard analysis adjusted for age at onset of panic and differences in demographic characteristics. Detection and treatment of panic may reduce the risk of developing major depression.

A second look at comorbidity in victims of trauma: the posttraumatic stress disorder–major depression connection

Background: We examine whether traumatic events increase the risk for major depression independent of their effects on posttraumatic stress disorder (PTSD). Methods: Data come from the Epidemiologic Study of Young Adults in southeast Michigan ( N = 1007). Retrospective and prospective data were used to estimate the risk of major depression in persons with PTSD and persons exposed to trauma with no PTSD, compared with persons who did not experience a trauma. National Comorbidity Survey data were used to evaluate the influence of trauma type. Results: In the retrospective lifetime data, hazard ratios were, for first-onset major depression in exposed persons with PTSD, 2.8 and, in exposed persons with no PTSD, 1.3 (not significant), as compared with persons who were not exposed. Corresponding estimates from the prospective data were 11.7 and 1.4 (not significant). The difference in the risk for depression associated with PTSD versus exposure without PTSD is unlikely to be due to differences in trauma type. Conclusions: The findings of a markedly increased risk for major depression in persons with PTSD, but not in exposed persons without PTSD, do not support the hypothesis that PTSD and major depression in trauma victims are influenced by separate vulnerabilities.

Psychosocial predictors of first-onset depression in Chinese Americans.

This study examines the longitudinal and concurrent risk factors associated with first-onset major depression in a community sample of 1747 Chinese Americans in Los Angeles. The relative contributions of demographic, health, psychiatric, psychosocial, and cultural variables were assessed in a series of longitudinal and concurrent hierarchical multivariable analyses. Results of the longitudinal analyses indicated that the risk for experiencing a first major depressive episode at 18-months follow-up was higher for those who initially rated their health as poor, reported higher depressive symptoms, and perceived higher levels of social support. After controlling for prior health and psychiatric and psychosocial status at time 1, the results of the concurrent analyses indicated that the risk for experiencing a first major depressive episode at time 2 was higher for those who rated their health as poor, had at least one other psychiatric disorder, were bilingual, experienced high levels of life stress, and perceived themselves as having low and/or decreased social supports. The results of this study confirm previous evidence that psychosocial vulnerabilities, including higher acculturation, greater stress exposure and reduced social supports, are important predictors of risk for first-onset depressive episodes. Prevention and treatment implications are addressed, and future directions for research are offered.

Headache and major depression: is the association specific to migraine?

To examine the relationship between migraine and major depression, by estimating the risk for first-onset major depression associated with prior migraine and the risk for first migraine associated with prior major depression. We also examined the extent to which comorbidity with major depression is specific to migraine or is observed in other severe headaches. Representative samples of persons 25 to 55 years of age with migraine or other severe headaches (i.e., disabling headaches without migraine features) and controls with no history of severe headaches were identified by a telephone survey and later interviewed in person to ascertain history of common psychiatric disorders. Lifetime prevalence of major depression was approximately three times higher in persons with migraine and in persons with severe headaches compared with controls. Significant bidirectional relationships were observed between major depression and migraine, with migraine predicting first-onset depression and depression predicting first-onset migraine. In contrast, persons with severe headaches had a higher incidence of first-onset major depression (hazard ratio = 3.6), but major depression did not predict a significantly increased incidence of other severe headaches (hazard ratio = 1.6). The contrasting results regarding the relationship of major depression with migraine versus other severe headaches suggest that different causes may underlie the co-occurrence of major depression in persons with migraine compared with persons with other severe headaches.

The morbidity of insomnia uncomplicated by psychiatric disorders

The morbidity of sleep problems has been well documented; however, they are frequently associated with and are symptomatic of several psychiatric disorders. It is unclear how much of the morbidity can be accounted for by the associated psychiatric and substance abuse disorders and medical problems, and how much by the sleep problems per se. Sleep problems may also be an early sign of a psychiatric problem. This paper reports data from an epidemiologic community survey of over 10,000 adults living in three U.S. communities. A structured diagnostic assessment of psychiatric disorders as well as assessment of the presence of insomnia not due to medical conditions, medication, drug or alcohol abuse, and a 1-year follow-up were completed. Persons with insomnia in the past year without any psychiatric disorders ever (uncomplicated insomnia); with a psychiatric disorder in the past year (complicated insomnia); and with neither insomnia nor psychiatric disorders ever were compared on treatment utilization and the first onset of a psychiatric disorder in the subsequent year. Eight percent of those with uncomplicated as compared with 14.9% with complicated insomnia and 2.5% with neither had sought treatment from the general medical sector for emotional problems in the 6 months prior to the interview. The rates of treatment sought from the psychiatric specialty sector were 3.8%, 9.4%, and 1.2%, respectively. These differences were significant after controlling for sociodemographic characteristics and were sustained when the persons were interviewed 1 year later. Uncomplicated insomnia was also associated with an increase in risk for first onset of major depression, panic disorder, and alcohol abuse over the following year. Insomnia, even in the absence of psychiatric disorders, is associated with increased use of general medical and mental health treatment for emotional problems and for the subsequent first onset in the following year of some psychiatric disorders. Early diagnosis and treatment of uncomplicated insomnia may be useful.

The effects of stressful life events on depression.

This chapter reviews recent research on the relationship between stressful life experiences and depression. A distinction is made between aggregate studies of overall stress effects and focused studies of particular events and difficulties. A distinction is also made between effects of life stress on first onset of depression and on the subsequent course of depression. Although the available evidence suggests that acute stressful life events can lead to the recurrence of episodes of major depression, a series of methodological problems compromise our ability to make clear causal inferences about the effects of life events on first onset of major depression or about the effects of chronic stress on either onset or recurrence of depression. The main problems of this sort are discussed, and recommendations made for ways of addressing these problems in future studies.