Reconsidering the prognosis of major depressive disorder across diagnostic boundaries:Full recovery is the exception rather than the rule

Background: Major depressive disorder (MDD) is often handled as an episodic and isolated disorder, resulting in an optimistic view about its prognosis. Herein, we test the idea that the prognosis of MDD changes if we vary the perspective in terms of (1) a longer time frame and (2) a broader diagnostic conceptualisation including dysthymia, (hypo) mania and anxiety disorders as relevant outcomes. Methods: Patients with current MDD at baseline (n = 903) and available 2-, 4-, and/or 6-year follow-up assessments were selected from the Netherlands Study of Depression and Anxiety, a psychiatric cohort study. Combining psychiatric DSM-IV-based diagnoses and life-chart data, patient course trajectories were classified as (1) recovered (no diagnoses at 2-year follow-up or thereafter), (2) recurrent without chronic episodes, (3) recurrent with chronic episodes or (4) consistently chronic since baseline. A chronic episode was defined as having a current diagnosis at the follow-up assessment and consistent symptoms over 2 years. Proportions of course trajectories were provided moving from a short, narrow perspective (2-year follow-up, considering only MDD diagnosis) to a long, broad perspective (6-year follow-up, including MDD, dysthymia, (hypo) mania and anxiety diagnoses). Results: With the short, narrow perspective, the recovery rate was 58% and 21% had a chronic episode. However, in the long, broad perspective the recovery rate was reduced to 17%, while 55% of the patients experienced chronic episodes. Conclusions: Results from a long and rigorous follow-up in a large cohort suggests that most MDD patients have an unfavourable prognosis. Longer follow-up and broader diagnostic conceptualisation show that the majority of patients have a disabling and chronic disorder. Conceptualising and handling MDD as a narrowly defined and episodic disorder may underestimate the prognosis of the majority of depressed patients and, consequently, the type of care that is appropriate

The role of explicit and implicit self-esteem in the relationship between childhood trauma and adult depression and anxiety

Background: Self-esteem is an important psychological concept that can be measured explicitly (reflective processing) and implicitly (associative processing). The current study examined 1) the association between childhood trauma (CT) and both explicit and implicit self-esteem, and 2) whether self-esteem mediated the association between CT and depression/anxiety. Methods: In 1479 adult participants of the Netherlands Study of Depression and Anxiety, CT was assessed with a semi-structured interview, depression/anxiety symptoms with self-report questionnaires and explicit and implicit self-esteem with the Rosenberg Self-Esteem Scale and Implicit Association Test, respectively. ANOVAs and regression analyses determined the association between CT (no/mild/severe CT), its subtypes (abuse/neglect) and self-esteem. Finally, we examined whether self-esteem mediated the relationship between CT and depression/anxiety. Results: Participants with CT reported lower explicit (but not lower implicit) self-esteem compared to those without CT (p < .001, partial η2 = 0.06). All CT types were associated with lower explicit self-esteem (p = .05 for sexual abuse, p < .001 for other CT types), while only emotional neglect significantly associated with lower implicit self-esteem after adjusting for sociodemographic characteristics (p = .03). Explicit self-esteem mediated the relationship between CT and depression/anxiety symptoms (proportion mediated = 48–77 %). Limitations: The cross-sectional design precludes from drawing firm conclusions about the direction of the proposed relationships. Conclusions: Our results suggested that the relationship between CT and depression/anxiety symptoms can at least partly be explained by explicit self-esteem. This is of clinical relevance as it points to explicit self-esteem as a potential relevant treatment target for people with CT

Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length

Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) 350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.Peer reviewe

Telomere length as a marker of cellular aging is associated with prevalence and progression of metabolic syndrome

Metabolic syndrome (MetS) represents a cluster of major risk factors known to be associated with the development of aging-related diseases, such as cardiovascular disease and diabetes. Telomere length (TL) is often used as a cellular marker for biological age. Shorter TL indicates increased biological age. It is unknown whether maintenance of a short TL could be predictive for onset of metabolic diseases associated with increasing biological age. A number of studies found significant associations between shorter TL and dysregulated MetS components, but other studies did not confirm this finding. This cohort study investigated the relationship between shorter baseline TL and a worse metabolic profile with less favorable trajectories of MetS components over a 6-year follow-up. Participants included 2842 men and women aged 18 to 65 years who were part of The Netherlands Study of Depression and Anxiety, an ongoing prospective cohort study with 6-year follow-up. Telomere length from leukocytes was determined using quantitative polymerase chain reaction. Metabolic syndrome components (waist circumference, triglycerides, high-density lipoprotein [HDL], cholesterol, fasting glucose, and systolic and diastolic blood pressure) were determined at baseline and after 2 and 6 years. Adjustments were made at baseline and 2- and 6-year follow-up for covariates (sociodemographic, lifestyle, and health factors) that could affect cross-sectional and longitudinal analyses

Unraveling the association between depression and telomere length using genomics

OBJECTIVE: While there is robust evidence for a cross-sectional association between depression and shorter telomere length, suggestive of advanced biological aging, the nature of this association remains unclear. Here, we tested whether both traits share a common genetic liability with novel methods using genomics. METHODS: Data were from 2032 participants of the Netherlands Study of Depression and Anxiety (NESDA) with genome-wide genetic information and multiple waves of data on DSM-IV lifetime depression diagnosis, depression severity, neuroticism and telomere length. Polygenic risk scores (PRS) for both traits were built using summary results from the largest genome-wide association studies (GWAS) on depression (59,851 cases and 113,154 controls) and telomere length (37,684 samples). Additionally, a PRS for neuroticism was built (337,000 samples). Genetic overlap between the traits was tested using PRS for same- and cross-trait associations. Furthermore, GWAS summary statistics were used to estimate the genome-wide genetic correlation between traits. RESULTS: In NESDA data, the PRS for depression was associated with lifetime depression (odds ratio = 1.36; p = 6.49e-7) and depression severity level (β = 0.13; p = 1.24e-8), but not with telomere length. Similar results were found for the PRS for neuroticism. Conversely, the PRS for telomere length was associated with telomere length (β = 0.07; p = 8.42e-4) and 6-year telomere length attrition rate (β = 0.04; p = 2.15e-2), but not with depression variables. In summary-level analyses, the genetic correlation between the traits was small and not significant (rg=-0.08; p = .300). CONCLUSION: The use of genetic methods in this paper indicated that the established phenotypic association between telomere length and depression is unlikely due to shared underlying genetic vulnerability. Our findings suggest that short telomeres in depressed patients may simply represent a generic marker of disease or may originate from non-genetic environmental factors

The role of explicit and implicit self-esteem in the relationship between childhood trauma and adult depression and anxiety

BackgroundSelf-esteem is an important psychological concept that can be measured explicitly (reflective processing) and implicitly (associative processing). The current study examined 1) the association between childhood trauma (CT) and both explicit and implicit self-esteem, and 2) whether self-esteem mediated the association between CT and depression/anxiety.MethodsIn 1479 adult participants of the Netherlands Study of Depression and Anxiety, CT was assessed with a semi-structured interview, depression/anxiety symptoms with self-report questionnaires and explicit and implicit self-esteem with the Rosenberg Self-Esteem Scale and Implicit Association Test, respectively. ANOVAs and regression analyses determined the association between CT (no/mild/severe CT), its subtypes (abuse/neglect) and self-esteem. Finally, we examined whether self-esteem mediated the relationship between CT and depression/anxiety.ResultsParticipants with CT reported lower explicit (but not lower implicit) self-esteem compared to those without CT (p &lt; .001, partial η2 = 0.06). All CT types were associated with lower explicit self-esteem (p = .05 for sexual abuse, p &lt; .001 for other CT types), while only emotional neglect significantly associated with lower implicit self-esteem after adjusting for sociodemographic characteristics (p = .03). Explicit self-esteem mediated the relationship between CT and depression/anxiety symptoms (proportion mediated = 48–77 %).LimitationsThe cross-sectional design precludes from drawing firm conclusions about the direction of the proposed relationships.ConclusionsOur results suggested that the relationship between CT and depression/anxiety symptoms can at least partly be explained by explicit self-esteem. This is of clinical relevance as it points to explicit self-esteem as a potential relevant treatment target for people with CT