Primary emotions as predictors for fear of COVID-19 in former inpatients with Major Depressive Disorder and healthy control participants.

INTRODUCTION: There are reports of an increase in depressive symptoms and fear during the COVID-19 pandemic, in particular in patients with depression. This study investigates factors related to fear of COVID-19 in former inpatients suffering from depression and healthy controls by assessing variables typically associated with depression and anxiety disorders, i.e. stressful life events (SLEs), the primary emotions SADNESS, PLAY and SEEKING as well as dysfunctional emotion regulation strategies with respect to suppression and reappraisal. METHODS: Data of n = 44 former inpatients suffering from depression and n = 49 healthy controls were collected. The study had a longitudinal design with two measurement points. Before the pandemic, SLEs, primary emotions, emotion regulation and depression severity were assessed. During the pandemic, COVID-19 associated stressors and life events, emotion regulation, depression severity and fear of COVID-19 were assessed. RESULTS: Fear of COVID-19 and depression severity during the pandemic were significantly higher in former inpatients than in healthy controls. Depression diagnosis, SLEs and depression severity before the pandemic were significant positive predictors of fear of COVID-19. The primary emotion PLAY was a significant negative predictor of fear of COVID-19. Depression severity did not change significantly in healthy controls. CONCLUSION: The results show that risk factors for depression might be risk factors for high fear of COVID-19. In addition, a playful personality could help preventing mental stress in pandemic situations. Thus, positivity based interventions could counteract elevated fear scores during a pandemic.

Factors related to age at depression onset: the role of SLC6A4 methylation, sex, exposure to stressful life events and personality in a sample of inpatients suffering from major depression.

BACKGROUND: An early onset of depression is associated with higher chronicity and disability, more stressful life events (SLEs), higher negative emotionality as described by the primary emotion SADNESS and more severe depressive symptomatology compared to depression onset later in life. Additionally, methylation of the serotonin transporter gene (SLC6A4) is associated with SLEs and depressive symptoms. METHODS: We investigated the relation of SLEs, SLC6A4 methylation in peripheral blood, the primary emotions SADNESS and SEEKING (measured by the Affective Neuroscience Personality Scales) as well as depressive symptom severity to age at depression onset in a sample of N = 146 inpatients suffering from major depression. RESULTS: Depressed women showed higher SADNESS (t (91.05) = - 3.17, p = 0.028, d = - 0.57) and higher SLC6A4 methylation (t (88.79) = - 2.95, p = 0.02, d = - 0.55) compared to men. There were associations between SLEs, primary emotions and depression severity, which partly differed between women and men. The Akaike information criterion (AIC) indicated the selection of a model including sex, SLEs, SEEKING and SADNESS for the prediction of age at depression onset. SLC6A4 methylation was not related to depression severity, age at depression onset or SLEs in the entire group, but positively related to depression severity in women. CONCLUSIONS: Taken together, we provide further evidence that age at depression onset is associated with SLEs, personality and depression severity. However, we found no associations between age at onset and SLC6A4 methylation. The joint investigation of variables originating in biology, psychology and psychiatry could make an important contribution to understanding the development of depressive disorders by elucidating potential subtypes of depression.

Group differences in OXT methylation between patients with Major Depressive Disorder and healthy controls: A pre-registered replication study.

Depression is linked to stress which leaves traces in the epigenetic signature of genes. The oxytocin system is implicated in allostatic processes promoting adaption to environmental stressors. Interactions of the oxytocin system with the environment, e.g., methylation of the gene coding for oxytocin (OXT), are candidates for the investigation of the biological underpinnings of depression. Recently, we found hypomethylation of OXT in patients with Major Depressive Disorder (MDD) compared to healthy controls (HC). Since the replicability of findings is a key point of criticism in (epi­)genetic research, we aimed to confirm our previous findings in a pre-registered study (data was stored in a database prior to pre-registration) within a new sample of n = 85 patients with MDD and n = 85 HC. We investigated OXT DNA-methylation in peripheral blood samples, stressful life events and depression severity. In accordance with our previous study, we found hypomethylation of OXT in patients with MDD compared to HC. Methylation was not associated with stressful life events. Patients reported significantly more stressful life events compared to HC. Our study revealed that hypomethylation of OXT can be demonstrated in a reproducible fashion and provides further evidence for the involvement of the oxytocin system in depression.

Association between parental separation, childhood trauma, neuroticism, and depression: a case control study.

Background: Parental separation has been suggested to be associated with depression development in offspring. The new family constellation subsequent to separation could be associated with elevated scores of childhood trauma, shaping more emotionally instable personalities. This could ultimately be a risk factor for mood disorders and particularly the development of depression in life. Methods: To test this hypothesis, we investigated the associations between parental separation, childhood trauma (CTQ) and personality (NEO-FFI) in a sample of N = 119 patients diagnosed with depression and N = 119 age and sex matched healthy controls. Results: While parental separation was associated with elevated scores of childhood trauma, there was no association between parental separation and Neuroticism. Furthermore, in a logistic regression analysis, Neuroticism and childhood trauma were found to be significant predictors for depression diagnosis (yes/no), but not parental separation (yes/no). Conclusion: Parental separation might be associated with depression only indirectly via childhood trauma. Childhood trauma or Neuroticism seem more directly related to the development of depression. However, it is worthwhile to install prevention programs helping parents and children to cope with parental separation in order to minimize the impact of separation and associated stressors.

Cumulative Genetic Score of DRD2 Polymorphisms Is Associated with Impulsivity and Masked Semantic Priming.

Individual differences in the magnitude of semantic priming effects are associated with executive functions (EF). Striatal dopamine has been shown to be associated with EF as well as impulsivity and could therefore be associated with differences in the magnitude of semantic priming. We investigated n = 155 individuals in an unmasked as well as in a masked semantic priming paradigm. We additionally assessed self-reported impulsivity and a cumulative genetic score (CGS) comprising six polymorphisms that have been found to be functionally relevant for the expression of the DRD2 gene. We found a significantly negative association between the DRD2 CGS and reaction time priming in the masked semantic priming paradigm. In addition, the DRD2 CGS was positively associated with self-reported impulsivity. Our findings complement previous research by showing a role of the DRD2 gene for masked semantic priming. Therefore, the investigation of genes within the dopamine system might improve our understanding of the genetic basis of impulsivity and semantic processing. Thus, the DRD2 CGS is of interest for clinical as well as experimental psychological research.

The Influence of the BDNF Val66Met Polymorphism on Mechanisms of Semantic Priming: Analyses with Drift-Diffusion Models of Masked and Unmasked Priming.

Automatic and strategic processes in semantic priming can be investigated with masked and unmasked priming tasks. Unmasked priming is thought to enable strategic processes due to the conscious processing of primes, while masked priming exclusively depends on automatic processes due to the invisibility of the prime. Besides task properties, interindividual differences may alter priming effects. In a recent study, masked and unmasked priming based on mean response time (RT) and error rate (ER) differed as a function of the BDNF Val66Met polymorphism (Sanwald et al., 2020). The BDNF Val66Met polymorphism is related to the integrity of several cognitive executive functions and might thus influence the magnitude of priming. In the present study, we reanalyzed this data with drift-diffusion models. Drift-diffusion models conjointly analyze single trial RT and ER data and serve as a framework to elucidate cognitive processes underlying priming. Masked and unmasked priming effects were observed for the drift rates ν, presumably reflecting semantic preactivation. Priming effects on nondecision time t0 were especially pronounced in unmasked priming, suggesting additional conscious processes to be involved in the t0 modulation. Priming effects on the decision thresholds a may reflect a speed-accuracy tradeoff. Considering the BDNF Val66Met polymorphism, we found lowered drift rates and decision thresholds for Met allele carriers, possibly reflecting a superficial processing style in Met allele carriers. The present study shows that differences in cognitive tasks between genetic groups can be elucidated using drift-diffusion modeling.

Depressive Emotionality Moderates the Influence of the BDNF Val66Met Polymorphism on Executive Functions and on Unconscious Semantic Priming.

Automatic semantic processing can be assessed using semantic priming paradigms. Individual differences in semantic priming have been associated with differences in executive functions. The brain-derived neurotrophic factor (BDNF) Val66Met (substitution of valine (Val) to methionine (Met) at codon 66) polymorphism has been shown to be associated with executive functions as well as depression. Depression-associated variables such as depressed mood also moderated the relationship between BDNF Val66Met and executive functions in previous work. In this study, we therefore aimed at investigating whether BDNF Val66Met genotype modulates masked and unmasked semantic priming as well as executive functions and whether sadness is a moderator of these associations. We collected data of N = 155 participants measuring reaction times (RTs) as well as error rates (ERs) in masked and unmasked semantic priming paradigms using a lexical decision task. We assessed the primary emotion of SADNESS using the Affective Neuroscience Personality Scale (ANPS) and working memory using digit span forward and backward tasks. Met+ carriers showed reduced RT priming and increased ER priming in the masked priming paradigm. Even though there was no direct association between BDNF Val66Met and executive functions, SADNESS significantly moderated the association between BDNF Val66Met and executive functions as well as masked RT priming. We suggest that Met+ individuals with low depressive tendencies have not only superior EF, but also a faster and more superficial processing style, compared with Val/Val homozygotes. However, in Met+ individuals, cognitive functioning exhibits a greater vulnerability to depressed emotionality compared with Val/Val homozygotes. Our study thus demonstrates how emotional and molecular genetic factors exert an interacting influence on higher-level cognition.

Relation of promoter methylation of the structural oxytocin gene to critical life events in major depression: A case control study.

BACKGROUND: Stressful life events (SLEs) are associated with hyper(re-)activity of the HPA-axis. HPA-axis hyper(re-)activity is thought to be a major risk factor for depression development. SLEs may induce changes in an organism's stress system via epigenetic mechanisms. The neuropeptide oxytocin (OT) is able to attenuate the stress response, and OT pathways are dysregulated in individuals suffering from Major Depressive Disorder (MDD). Therefore, the gene coding for oxytocin (OXT) is a possible target for the investigation of depression development. METHODS: We collected data on SLEs, OXT promoter methylation (Sequenom Epityper MassArray) and depression severity from 90 MDD inpatients and 90 matched healthy controls. RESULTS: We found MDD inpatients to have a significantly lower OXT methylation than healthy controls. Methylation status was significantly negatively associated with SLEs but only in the group of MDD inpatients. There were no associations between methylation status and depression severity. LIMITATIONS: Methylation in blood samples is only a proxy for epigenetic profiles in brain tissue. We did not assess mRNA or protein levels and cannot draw conclusions regarding the functionality or specificity of differences in OXT methylation between groups. CONCLUSION: SLEs leave their traces in the epigenetic profiles of the OT system of MDD inpatients. Alterations in epigenetic profiles of the OXT system could constitute a vulnerability factor predisposing individuals for depression development. Better understanding of DNA methylation profiles of depression-associated genes could serve as basis for a personalized medicine, in which pharmacological or psychotherapeutic treatment of depression is tailored to the patient's individual characteristics.

Relation of Promoter Methylation of the Oxytocin Gene to Stressful Life Events and Depression Severity.

Oxytocin (OT) is a neuropeptide associated with trauma, sociality, and depression. Despite the widely accepted assumption of OT playing a role in the etiology of mood and anxiety disorders, associations between stressful life events, depression, and epigenetic regulation of the gene coding for OT (OXT) have not yet been investigated. We therefore aimed to examine the interrelations of stressful life events, depression severity, and methylation of the promoter region of OXT in a sample of N = 146 inpatients suffering from major depression. We found significant negative associations of stressful life events with mean methylation status as well as with methylation status of single CpG sites in the promoter region of OXT. There was no association between depression severity and OXT methylation. However, there were significant sex differences in methylation status of OXT with women showing higher methylation rates than men, putatively suggesting that in depression OXT is less activated in females compared to males. These results speak against an association of OXT methylation and depression severity, but support the assumption of a dysregulation of the OT system due to life stress. Our findings further emphasize the importance of including sex as an important factor in the investigation of the interrelations between OXT, stress, and depression.

Depression Is Associated With the Absence of Sex Differences in the 2D:4D Ratio of the Right Hand.

The 2D:4D digit ratio reflects prenatal testosterone relative to estradiol exposure of a developing embryo. Higher levels of prenatal testosterone have been related to lower 2D:4D ratios. In addition, higher 2D:4D ratios have been associated with female gender, neuroticism, and depression severity. Therefore, the present study investigated whether 2D:4D ratios differ between inpatients with major depression and matched healthy controls and whether 2D:4D ratios correlate with depression severity. We examined 139 inpatients diagnosed with major depression according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria and 137 healthy controls regarding 2D:4D ratios of both hands and BDI-II scores. While we observed significant sex differences in the 2D:4D ratio of the right hand in the healthy control group (women on average showed a significantly higher 2D:4D ratio), no such differences were found in the group of depressed patients. The 2D:4D digit ratios did not correlate with depression severity even when examined for group and sex separately. We conclude that major depression is associated with an absence of sex differences in the 2D:4D ratio.