Higher Risk Of Major Depressive Disorder Research Articles

Occupational factors associated with major depressive disorder: A Brazilian population-based study

BackgroundThere have been very few studies exploring the occupational risk factors for major depressive disorder (MDD) in the working populations in Latin America. The aim of this study was to explore the associations between a large set of occupational factors and MDD in the Brazilian working population. MethodsThe study was based on the cross-sectional data from the Brazilian National Health Survey, 2013. 60,202 people were interviewed (response rate: 91.9%). Among them, 36,442 were working, 19,450 men and 16,992 women. MDD was measured using the diagnostic algorithm (DSM-IV criteria) of the PHQ-9. Occupational factors included job characteristics, working time factors, psychosocial work stressors and physico-chemical exposures. Logistic regression models were performed and adjusted for sociodemographic factors. All analyses were conducted using weighted and stratified data by gender. ResultsThe following occupational factors were associated with a higher risk of MDD: working part time (≤20 h a week) and stress at work for both genders, workplace violence, intense physical activity, exposure to noise and chemicals among women, and prolonged exposure to sun among men. Associations of stress and violence at work with MDD were particularly strong. LimitationsCross-sectional study design, healthy worker effect and reporting bias may have impacted the results. ConclusionsThis study, one of the first studies among the Brazilian working population, showed that psychosocial work stressors were the strongest risk factors for MDD. Physico-chemical exposures deserve more attention in association with MDD. Prevention policies oriented toward the work environment may help to prevent depression at the workplace.

Classical Risk Factors and Inflammatory Biomarkers: One of the Missing Biological Links between Cardiovascular Disease and Major Depressive Disorder

Background: Cardiovascular disorders (CVD) and major depressive disorder (MDD) are the most frequent diseases worldwide responsible for premature death and disability. Behavioral and immunological variables influence the pathophysiology of both disorders. We therefore determined frequency and severity of MDD in CVD and studied whether MDD without CVD or other somatic diseases influences classical and inflammatory biomarkers of cardiovascular risk. In addition, we investigated the influence of proinflammatory cytokines on antidepressant treatment outcome. Methods: In a case-control design, 310 adults (MDD patients without CVD, CVD patients, and cardiologically and psychiatrically healthy matched controls) were investigated. MDD patients were recruited after admission in a psychiatric university hospital. Primary outcome criteria were clinical depression ratings (HAM-D scale), vital signs, classical cardiovascular risk factors and inflammatory biomarkers which were compared between MDD patients and healthy controls. Results: We detected an enhanced cardiovascular risk in MDD. Untreated prehypertension and signs directing to a metabolic syndrome were detected in MDD. Significantly higher inflammatory biomarkers such as the high sensitivity C-reaktive protein (hsCRP) and proinflammatory acute phase cytokines interleukine-1β (IL-1β) and interleukine-6 (IL-6) underlined the higher cardiovascular risk in physically healthy MDD patients. Surprisingly, high inflammation markers before treatment were associated with better clinical outcome and faster remission. The rate of MDD in CVD patients was high. Conclusions: Patients suffering from MDD are at specific risk for CVD. Precise detection of cardiovascular risks in MDD beyond classical risk factors is warranted to allow effective prophylaxis and treatment of both conditions. Future studies of prophylactic interventions may help to provide a basis for prophylactic treatment of both MDD and CVD. In addition, the high risk for MDD in CVD patients was confirmed and underlines the requirement for clinical attention.

Error-related brain activity in adolescents with obsessive-compulsive disorder and major depressive disorder.

The error-related negativity (ERN) is a negative deflection in the event-related potential following a mistake that is often increased in patients with obsessive-compulsive disorder (OCD). The relationship of the ERN to comorbid major depressive disorder (MDD) has not been examined in adolescents with OCD. This study compared ERN amplitudes in OCD patients with MDD (OCD+MDD), OCD patients without MDD (OCD-MDD), MDD patients, and healthy controls (HC). The ERN, correct response negativity, and accuracy were measured during a flanker task to assess performance monitoring in 53 adolescents with a lifetime diagnosis of OCD, 36 adolescents with a lifetime diagnosis of MDD, and 89 age-matched HC of 13-18 years. Fourteen OCD patients had a history of MDD. ERN amplitude was significantly increased in OCD patients compared to HC and significantly correlated in OCD patients with age at OCD symptom onset, particularly in the OCD - MDD patients. The ERN was significantly enlarged in OCD+MDD patients compared to HC, but not in MDD patients compared to HC. There was a trend for an increased ERN amplitude in OCD - MDD patients compared to HC. OCD patients were significantly less accurate than either MDD patients or HC. An enlarged ERN is a neural correlate of adolescent OCD that is associated with age at OCD symptom onset. Adolescents with OCD may have impaired cognitive control on a flanker task. Follow-up studies with larger samples may determine whether an enlarged ERN in adolescents with OCD is associated with a higher risk for MDD.

Neighborhood Safety and Major Depressive Disorder in a National Sample of Black Youth; Gender by Ethnic Differences.

Adolescence is a developmental period marked by increased stress, especially among Black youth. In addition to stress related to their developmental transition, social factors such as a perceived unsafe neighborhood impose additional risks. We examined gender and ethnic differences in the association between perceived neighborhood safety and major depressive disorder (MDD) among a national sample of Black youth. We used data from the National Survey of American Life - Adolescents (NSAL-A), 2003–2004. In total, 1170 Black adolescents entered the study. This number was composed of 810 African American and 360 Caribbean Black youth (age 13 to 17). Demographic factors, perceived neighborhood safety, and MDD (Composite International Diagnostic Interview, CIDI) were measured. Logistic regressions were used to test the association between neighborhood safety and MDD in the pooled sample, as well as based on ethnicity by gender groups. In the pooled sample of Black youth, those who perceived their neighborhoods to be unsafe were at higher risk of MDD (Odds Ratio [OR] = 1.25; 95% Confidence Interval [CI] = 1.02-1.51). The perception that one’s neighborhood is unsafe was associated with a higher risk of MDD among African American males (OR=1.41; 95% CI = 1.03–1.93) but not African American females or Caribbean Black males and females. In conclusion, perceived neighborhood safety is not a universal psychological determinant of MDD across ethnic by gender groups of Black youth; however, policies and programs that enhance the sense of neighborhood safety may prevent MDD in male African American youth.

Alcohol use and depression during adolescence and young adulthood: a summary and interpretation of mixed findings.

Alcohol Use Disorder (AUD) and alcohol misuse are common among adolescents and young adults and are associated with significant personal and societal problems. Similarly, Major Depressive Disorder (MDD) and depressive symptoms are prevalent in this population and when they co-occur with alcohol misuse lead to even more severe consequences. Numerous studies have investigated the association between depressive symptoms, AUD and various drinking behaviors presenting an unclear picture. In this review we summarize studies among adolescents and young adults that have examined these relationships. From this review it emerges that several factors affect results, including study design (cross-sectional vs longitudinal), participants' age (adolescents vs young adults), severity of problems considered (AUD vs heavy drinking; MDD vs depressive symptoms), and gender. Adolescents with AUD are at higher risk for MDD in particular at a younger age. During adolescence, several drinking behaviors, including weekly alcohol use and heavy drinking, increase the risk for depressive symptoms and MDD, while during young adulthood primarily AUD, but not other drinking behaviors, is associated with increased risk for MDD. Gender may have an effect on the association between depression and drinking behaviors but its role is still unclear. Some evidence suggests that the association between AUD and MDD is bidirectional such that mood problems contribute to the onset of alcohol problems and vice-versa. More longitudinal studies are needed to examine these associations in young adults and to clarify the effect of gender on these associations. To date, findings suggest the critical need to reduce any alcohol use at a young age and to treat both depressive symptoms and AUD to prevent the occurrence of comorbid disorders.

The serotonin transporter gene (triallelic 5-HTTLPR polymorphism) may associate with male depression in Han Chinese population

Background: Pharmacological, neurobehavioral, and therapeutic evidence have implicated serotonin in the pathogenesis of depression. There are conflicting reports on the association of genetic variants of serotonin transporter gene (5-HTTLPR) with major depressive disorder. The 5-HTTLPR is thought to have three primary allelic variants (rs25531): LA, LG, and S. The present study examined whether major depression was associated with tri-allelic 5-HTTLPR polymorphisms in a Han Chinese population. Materials and Methods: Bi-allelic and tri-allelic 5-HTTLPR polymorphisms were assessed in 305 patients with major depressive disorder (MD) and 313 unrelated healthy control subjects. In addition, to reduce clinical heterogeneity, subtype analyses were performed for clinically important variables, including family history of major affective disorder, age at onset, and severity of MD. Results: The bi-allelic 5-HTTLPR polymorphism was not associated with MD and its clinical subgroups. However, the tri-allelic 5-HTTLPR polymorphism was associated with major depression and with specific subgroups. In particular, in male subjects, patients with a low expressing genotype ( S'/S' ) were at higher risk for MD than those with high expressing genotypes ( S'/L' and L'/L' ). This positive association was only observed in the subgroups of late-onset and moderate severity MD. Conclusions: The present study suggests that the tri-allelic 5-HTTLPR polymorphism might be a risk factor for susceptibility to either MD or its clinical subtypes in the Han Chinese male population but not in the female population. However, these results should be validated in a larger patient population that includes different ethnic samples or subdiagnosis groups.

Predictors of first lifetime onset of major depressive disorder in young adulthood.

The first onset of major depressive disorder (MDD) most frequently occurs in young adulthood. However, few studies have examined predictors of first lifetime MDD during this high-risk period. The present study examined a broad range of demographic, clinical, and psychosocial variables as prospective predictors of first onset of MDD in a large community sample of young adults (N = 502) from the Oregon Adolescent Depression Project. Between ages 19-31, 35.3% of the sample had a first lifetime MDD episode. Female gender, familial loading of mood disorders, history of childhood sexual abuse, prior history of anxiety disorder, poor self-reported physical health, and subthreshold depressive symptoms significantly predicted MDD onset. In a multivariate model, female gender, familial loading of mood disorders, and subthreshold depression each contributed unique variance in predicting first lifetime MDD. This model had a moderate-to-large effect in predicting MDD onset. Gender did not moderate the other predictors, and the magnitude of the effects did not diminish over the course of the follow-up. These findings indicate that a number of risk factors significantly predict first lifetime MDD in young adulthood, and that simple multivariate risk models may be useful for identifying individuals at high risk for MDD.

952 – A population-based longitudinal study on work environment and major depressive disorder

To investigate the relationships between work environmental factors and the risk of major depressive disorder (MDD) over one year and to identify factors associated with the outcomes of individuals with MDD. We conducted a population-based longitudinal study of employees who were randomly selected in Alberta (n = 4239). MDD was assessed using the World Health Organization's Composite International Diagnostic Interview - Auto 2.1. The one-year incidence of MDD was 3.6% (95% CI: 2.8%-4.6%) overall. It was 2.9% (95% CI: 1.9% - 4.2%) in men and 4.5% (95% CI: 3.3% - 6.2%) in women. The relationships between work environmental factors and MDD differed by sex. In men, high job strain increased the risk of MDD in those who worked 35-40 hours per week; job insecurity and family-work conflict were predictive of MDD. Women who worked 35-40 hours, who reported job insecurity, high effort-reward imbalance and work-family conflict were at higher risk of MDD. Long working hours, negative thinking and having comorbid social phobia were predictive of MDD. Perceived work-family conflict, severity of major depressive episode and symptom of depressed mood were significantly associated with recurrence of MDD. Job strain, effort-reward imbalance, job insecurity and work-family conflicts are important risk factors for the onset of MDD, and should be targets of primary prevention. However, these work environmental factors appear to operate differently in men and in women. Clinical and psychosocial factors are important in the prognosis of MDD. The factors associated with persistence and recurrence of MDD may be different.

Interaction between the BDNF gene Val/66/Met polymorphism and morning cortisol levels as a predictor of depression in adult women

Common genetic variants, such as the brain-derived neurotrophic factor (BDNF) Val/66/Met polymorphism (rs6265), are known to interact with environmental factors such as early adversity to increase the risk of subsequent major depression. Much less is known about how they interact with individual differences in cortisol, although these also represent a risk for major depression. To determine whether this BDNF variant moderated the risk represented by higher levels of morning salivary cortisol in adult women. We recruited 279 premenopausal women who were at high risk of major depressive disorder because of either negative self-evaluation, unsupportive core relationship or chronic subclinical symptoms of depression or anxiety. Morning salivary cortisol was measured daily for up to 10 days at entry. Participants were followed up for about 12 months by telephone calls at 3-4 monthly intervals. Major depression and severe life events were assessed through interviews at baseline and follow-up; DNA was obtained from the saliva. There were 53 onsets (19%) of depressive episodes during follow-up. There was a significant U-shaped relationship between adjusted morning cortisol levels at baseline and the probability of depression onset during follow-up. In total, 51% experienced at least one severe life event/difficulty, and this strongly predicted subsequent onsets of depressive episodes. The BDNF Val/66/Met genotype was not directly associated with onsets of depression or with cortisol levels, but there was significant interaction between Val/66/Met and cortisol: the association between baseline cortisol and depression was limited to those with the Val/66/Val variant. There was no interaction between life events and either this BDNF polymorphism or cortisol levels. Morning salivary cortisol interacts with the BDNF Val/66/Met polymorphism in predicting new depressive episodes. This paper adds to the evidence that single gene polymorphisms interact with endogenous factors to predict depression.

Analysis of genetic polymorphisms of brain-derived neurotrophic factor and methylenetetrahydrofolate reductase in depressed patients in a Slovak (Caucasian) population

Major depressive disorder (MDD) is a complex neuropsychiatric disorder where both gene-gene and gene-environment interactions play an important role, but the clues are still not fully understood. One carbon metabolism in the CNS plays a critical role in the synthesis and release of neurotransmitters which are relevant to depressive disorder. We studied genetic polymorphisms of the brain derived neurotrophic factor (BDNF) and the methylenetetrahydrofolate reductase (MTHFR) in association with major depressive disorder. We genotyped the BDNF G196A, the MTHFR C677T, and A1298C polymorphisms in 134 patients diagnosed with major depression and 143 control subjects in Slovak (Caucasian) cohort of patients and probands. We found no significant association of either the BDNF G196A or MTHFR C677T polymorphisms with major depressive disorder neither in female nor male group of patients. However, the MTHFR A1298C genotype distribution was 36.6% (for AA genotype), 48.5% (AC) and 14.9% (CC) for the depressed patients, and 48.9% (AA), 42.7% (AC) and 8.4% (CC), respectively, for the control subjects. Patients with MDD had a higher prevalence of the CC genotype (OR = 2.38; 95% CI = 1.07-5.32; p = 0.032) and the AC + CC genotype (OR = 1.67; 95% CI = 1.03-2.69; p = 0.037) in comparison with the control subjects. This study shows that CC genotype of the MTHFR A1298C is associated with higher risk of MDD in Slovak population.

Economic consequence of switching to citalopram after its generic entry for adult patients with major depressive disorder (MDD) treated with escitalopram: a 6-month retrospective study

Objective:To estimate, from a third-party payer's perspective, the effects of switching from escitalopram to citalopram, after the generic entry of citalopram, on hospitalization and healthcare costs among adult MDD patients who were on escitalopram therapy.Methods:Adult MDD patients treated with escitalopram were identified from Ingenix Impact claims database. MDD- and mental health (MH)-related hospitalization rates and healthcare costs were compared between ‘switchers’ (patients who switched to citalopram after its generic entry) and ‘non-switchers’. MDD- and MH-related outcomes were defined as having a primary or a secondary diagnosis of ICD-9-CM = 296.2x, 296.3x and ICD-9-CM = 290–319, respectively. A propensity score matching method that estimated the likelihood of switching using baseline characteristics was used. Outcomes were examined for both 3-month and 6-month post-index periods.Results:The sample included 3,427 matched pairs with balanced baseline characteristics. Switchers were more likely to incur an MDD-related (odds ratio [OR] = 1.52) and MH-related hospitalization (OR = 1.34) during the 6-month post-index period (both p < 0.05). Compared to switchers, non-switchers had significantly lower MDD- and MH-related hospitalization costs ($248.3 and $219.8 lower, respectively) and medical costs ($277.4 and $246.4 lower, respectively) (all p < 0.05). Although non-switchers had significantly higher MDD- and MH-related prescription drug costs, overall they had significantly lower total MDD- and MH-related healthcare costs ($109.9 and $93.6 lower, respectively; both p < 0.001). The 3-month results were consistent with these 6-month findings.Limitations:The study limitations included limited generalizability of study findings, inability to differentiate switching from escitalopram to citalopram due to medical reasons versus non-medical reasons, and exclusion of indirect costs from cost calculations.Conclusions:Compared to patients maintaining on escitalopram, switchers from escitalopram to citalopram experienced higher risk of MDD- and MH-related hospitalization and incurred higher total MDD- and MH-related healthcare costs. The economic consequences of therapeutic substitution should take into account total healthcare costs, not just drug acquisition costs.

Reduced Sleep Spindle Activity in Early-Onset and Elevated Risk for Depression

Sleep disturbances are common in major depressive disorder (MDD), although polysomnographic (PSG) abnormalities are more prevalent in adults than in children and adolescents with MDD. Sleep spindle activity (SPA) is associated with neuroplasticity mechanisms during brain maturation and is more abundant in childhood and adolescence than in adulthood, and as such, may be a more sensitive measure of sleep alteration than PSG in early-onset depression. This study investigated SPA changes related to early-onset MDD, comparing individuals already ill with MDD and individuals at high-risk for MDD with healthy nondepressed controls. The study included 63 participants (8 to 15 years of age): 21 currently depressed individuals, 21 individuals at high risk for MDD based on positive family history of MDD, and 21 healthy control individuals with no personal or family history of psychiatric illness. All participants maintained a regular sleep/wake schedule for 5 days, followed by 2 nights in the laboratory. SPA was analyzed in Stage 2 of non-rapid eye movement sleep. SPA differed significantly between groups, particularly in the late part of the night (F(2,62) = 7.3, p = .001). Although the difference was greatest between the MDD and healthy control groups, both the MDD (p = .0004) and at high-risk groups (p = .02) had significantly lower SPA compared with healthy controls. SPA deficit was more prominent in females than in males (F(5,62) = 5.19, p = .005). Low SPA characterizes youths with MDD and those at high risk for MDD, particularly girls, suggesting that early-onset depression and risk for the MDD are associated with decreased neuroplasticity.

Expressed Emotion in Mothers of Currently Depressed, Remitted, High-Risk, and Low-Risk Youth: Links to Child Depression Status and Longitudinal Course

This study examined expressed emotion in the families of children and adolescents who were (a) in a current episode of Major Depressive Disorder (MDD), (b) in remission from a past episode of MDD, (c) at high familial risk for developing MDD, and (d) low-risk controls. Participants were 109 mother–child dyads (children ages 8–19). Expressed emotion was assessed using the Five Minute Speech Sample, and psychiatric follow-ups were conducted annually. Mothers of children with a current or remitted episode of MDD and at high risk for MDD were more likely to be rated high on criticism than mothers of controls. There were no differences in critical expressed emotion among mothers of children in the current, remitted, or high-risk for depression groups. Higher initial critical expressed emotion was associated with a greater likelihood of having a future onset of a depressive episode in high-risk and depressed participants. Diagnostic groups did not differ in Emotional Overinvolvement.

The characteristics of asymptomatic female adolescents at high risk for depression: the baseline assessment from a prospective 8-year study

Objective: This longitudinal 8-year study assesses potential predictors of major depressive disorder (MDD) in a cohort of healthy adolescent females at high familial risk for MDD. The objective of this study was to ascertain whether risk factors for female onset MDD would differentiate youth at high or usual risk for MDD, prior to the onset of depressive symptomology. Method: Subjects (ages 12–15 years) were assigned to a high ( n=43) or usual ( n=40) risk group according to maternal history of MDD. Depressive symptomatology (Beck Depression Inventory, Hamilton Rating Scale for Depression), pubertal development (Pubertal Developmental Staging Questionnaire), social support (Social Support Scale), and cognitive vulnerability (Depressive Experiences Questionnaire) were assessed. Results: High risk and usual risk group demonstrated no significant differences in demographic variables such as age, body mass index, and grade. Significantly more youth in the high risk group ( n=40, 93%) had started menstruation, compared to youth in the usual risk group ( n=31, 77.5%). There were no significant differences between the groups on measures of dysphoric cognitive style, perceived overall number of social supports, or satisfaction with social support. Conclusion: Females at high familial risk for the onset of depression have significant differences in pubertal development, but not in demographics, depressive symptoms, social supports, or dysphoric cognitive style, when compared to females at usual risk for depression. These findings suggest that in prevention trials for depression in asymptomatic young women no non-biological risk factors for MDD aid in identifying females at higher risk for MDD.

Neuroendocrine response to 5-hydroxy-L-tryptophan in prepubertal children at high risk of major depressive disorder.

Altered serotonergic function has been observed in prepubertal children and adults with an acute episode of major depressive disorder (MDD). However, it is not known whether these alterations are present prior to the onset of MDD. A serotonergic precursor, 5-hydroxy-L-tryptophan (L-5HTP) (oxitriptan) (0.8 mg/kg), was administered through an indwelling catheter to 36 children at high risk of MDD (with high family loading for MDD), 31 children with MDD, and 23 low-risk normal controls (with low family loading for mood disorders and no history of psychopathology). Blood samples for cortisol, prolactin (PRL), and growth hormone were obtained every 15 minutes for 180 minutes, beginning 30 minutes before L-5HTP infusion. Children at high risk of MDD and children with MDD had similar hormonal responses following L-5HTP infusion. After controlling for baseline values, both groups secreted significantly less cortisol and more PRL than did the low-risk normal controls, with the PRL finding being limited to girls. There were no between-group differences in baseline cortisol, PRL, or growth hormone secretion measures. Before the onset of affective illness, high-risk children had the same pattern of neuroendocrine response to the L-5HTP challenge as did children with MDD. These results extend earlier findings of altered serotonergic regulation in association with early-onset depression and indicate that these alterations may represent a trait marker for depression in children.