Comorbidity among affective disorders is high. Rumination has been found to mediate cross-sectional and prospective relations between anxiety and depressive symptoms in adolescents and adults. We ...examined whether rumination and worry, both forms of repetitive negative thinking, also explain the associations between affective disorders. This was studied using a prospective cohort study. In a mixed sample of 2981 adults (persons with a prior history of or a current affective disorder and healthy individuals) we assessed DSM-IV affective disorders (CIDI), rumination (LEIDS-R) and worry (PSWQ). All measures were repeated 2 years and 4 years later. Using structural equation models, we found that baseline rumination and worry partly mediated the association of baseline fear disorders (social anxiety disorder, panic disorder, agoraphobia) with distress disorders (dysthymia, major depressive disorder, generalized anxiety disorder). Moreover, baseline fear disorders predicted changes in distress disorders and changes in worry and rumination mediated these associations. The association between baseline distress disorders and changes in fear disorders was mediated by changes in rumination but not by changes in worry. From these results it can be concluded that repetitive negative thinking is an important transdiagnostic factor. Rumination and worry are partly responsible for the cross-sectional and prospective co-occurrence of affective disorders and may be suitable targets for treatment.
•Worry and rumination accounted for the co-occurrence of distress and fear disorders.•Fear disorders predicted subsequent changes in distress disorders and vice versa.•The longitudinal fear → distress association was mediated by worry and rumination.•The longitudinal distress → fear association was mediated by rumination, not worry.•The transdiagnostic factors worry/rumination are suitable targets for treatment.
Summary Introduction Depression and anxiety disorders have been associated with hyperactivity of the hypothalamic-pituitary adrenal (HPA) axis. However, lower cortisol levels have also been observed ...in depressed patients. Whether cortisol level predicts the course of these disorders has not been examined in detail. We examined whether salivary cortisol indicators predict the 2-year course of depression and anxiety disorders. Methods Longitudinal data are obtained from 837 participants of the Netherlands Study of Depression and Anxiety, with a DSM-IV based depressive and/or anxiety disorder at baseline. At baseline, seven saliva samples were obtained, including the 1-h cortisol awakening response, evening cortisol level and a 0.5 mg dexamethasone suppression test. At follow-up, DSM-IV based diagnostic interviews and Life Chart Interview integrating diagnostic and symptom trajectories over 2 years were administered to determine an unfavorable course. Results 41.5% of the respondents had a 2-year unfavorable course trajectory without remission longer than 3 months. Adjusted analyses showed that a lower awakening response was associated with an unfavorable course (RR = 0.83, p = 0.03). No associations were found between evening cortisol or cortisol suppression after dexamethasone ingestion and an unfavorable course trajectory. Conclusions Among patients with depressive or anxiety disorders, a lower cortisol awakening response – which may be indicative of underlying exhaustion of the HPA axis – predicted an unfavorable course trajectory.
Purpose
Adherence to the Mediterranean diet has been associated with fewer depressive symptoms, however, it is unknown whether this is attributed to some or to all components. We examined the ...association between the individual food groups of the Mediterranean Diet Score (MDS), in isolation and in combination, with depression and anxiety (symptom severity and diagnosis).
Methods
Data from 1634 adults were available from the Netherlands Study of Depression and Anxiety. Eleven energy-adjusted food groups were created from a 238-item food frequency questionnaire. In regression analysis, these were associated in isolation and combination with (1) depressive and anxiety disorders (established with the Composite International Diagnostic Interview) (current disorder
n
= 414), and (2) depression and anxiety severity measured with the Inventory of Depressive Symptomatology (IDS), the Beck Anxiety Inventory (BAI) and the Fear Questionnaire (FEAR).
Results
Overall, the MDS score shows the strongest relationships with depression/anxiety Diagnosis: odds ratio (OR) 0.77 per SD, 95% confidence interval (95% CI) 0.66–0.90, IDS: standardised betas (
β
) − 0.13, 95% CI − 0.18, − 0.08 and anxiety (BAI:
β
− 0.11, 95% CI − 0.16, − 0.06, FEAR:
β
− 0.08, 95% CI − 0.13, − 0.03). Greater consumption of non-refined grains and vegetables was associated with lower depression and anxiety severity, whilst being a non-drinker was associated with higher symptom severity. Higher fruit and vegetable intake was associated with lower fear severity. Non-refined grain consumption was associated with lower odds and being a non-drinker with greater odds of current depression/anxiety disorders compared to healthy controls, these associations persisted after adjustment for other food groups (OR 0.82 per SD, 95% CI 0.71–0.96, OR 1.26 per SD 95% CI 1.08–1.46).
Conclusion
We can conclude that non-refined grains, vegetables and alcohol intake appeared to be the driving variables for the associated the total MDS score and depression/anxiety. However, the combined effect of the whole diet remains important for mental health. It should be explored whether an increase consumption of non-refined grains and vegetables may help to prevent or reduce depression and anxiety.
Objectives
To examine whether overall depressive symptoms and symptom clusters are associated with fall risk and to determine whether chronic pain mediates the relationship between depression and ...fall risk in aging.
Design
Prospective cohort study.
Setting
Boston, Massachusetts, and surrounding communities.
Participants
Older community‐dwelling adults (N = 722, mean age 78.3).
Measurements
Depressive symptomatology was assessed at baseline using the 20‐item Hopkins Revision of the Center for Epidemiologic Studies Depression Scale (CESDR) as overall depression and two separate domains: cognitive and somatic symptoms. Chronic pain was examined at baseline as number of pain sites (none, single site, or multisite), pain severity, and pain interference with activities of daily living. Participants recorded falls on monthly postcards during a subsequent 18‐month period.
Results
According to negative binomial regression, the rate of incident falls was highest in those with the highest burden of depressive symptoms (according to total CESDR and the cognitive and somatic CESDR domains). After adjustment for multiple confounders and fall risk factors, fall rate ratios comparing the highest three CESDR quartiles with the lowest quartile were 1.91, 1.26, and 1.11, respectively. Similarly graded associations were observed according to the CESDR domains. Although pain location and interference were mediators of the relationship between depression and falls, adjustment for pain reduced fall risk estimates only modestly. There was no interaction between depression and pain in relation to fall risk.
Conclusion
Depressive symptoms are associated with fall risk in older adults and are mediated in part by chronic pain. Research is needed to determine effective strategies for reducing fall risk and related injuries in older people with pain and depressive symptoms.
Insomnia exhibits a clinically relevant relationship with major depressive disorder (MDD). Increasing evidence suggests that insomnia is associated with neurobiological alterations that resemble the ...pathophysiology of MDD. However, research in a clinical population is limited. The present study, therefore, aimed to investigate the relationship between insomnia and the main pathophysiological mechanisms of MDD in a clinical sample of individuals with MDD. Data were extracted from three cohorts (
= 227) and included an evaluation of depression severity (Quick Inventory of Depressive Symptomatology, QIDS-SR
) and insomnia severity (QIDS-SR
insomnia items) as well as serum and urine assessments of 24 immunologic (e.g., tumour necrosis factor α receptor 2 and calprotectin), neurotrophic (e.g., brain-derived neurotrophic factor and epidermal growth factor), neuroendocrine (e.g., cortisol and aldosterone), neuropeptide (i.e., substance P), and metabolic (e.g., leptin and acetyl-L-carnitine) biomarkers. Linear regression analyses evaluating the association between insomnia severity and biomarker levels were conducted with and without controlling for depression severity (
= 17.32), antidepressant use (18.9%), gender (59.0% female; 40.5% male), age (
= 42.04), and the cohort of origin. The results demonstrated no significant associations between insomnia severity and biomarker levels. In conclusion, for the included biomarkers, current findings reveal no contribution of insomnia to the clinical pathophysiology of MDD.
Exposure to early life stress (ELS), prenatal or postnatal during childhood and adolescence, can significantly impact mental and physical health. The role of the intestinal microbiome in human ...health, and particularly mental health, is becoming increasingly evident. This systematic review aims to summarize the clinical data evaluating the effect of ELS on the human intestinal microbiome. The systematic review (CRD42022351092) was performed following PRISMA guidelines, with ELS considered as exposure to psychological stressors prenatally and during early life (childhood and adolescence). Thirteen articles met all inclusion criteria, and all studies reviewed found a link between ELS and the gut microbiome in both prenatal and postnatal periods. However, we failed to find consensus microbiome signatures associated with pre- or postnatal stress, or both. The inconsistency of results is likely attributed to various factors such as different experimental designs, ages examined, questionnaires, timing of sample collection and analysis methods, small population sizes, and the type of stressors. Additional studies using similar stressors and validated stress measures, as well as higher-resolution microbiome analytical approaches, are needed to draw definitive conclusions about the links between stress and the human gut microbiome.
Which neighbourhood factors most consistently impact on depression and anxiety remains unclear. This study examines whether objectively obtained socioeconomic, physical and social aspects of the ...neighbourhood in which persons live are associated with the presence and severity of depressive and anxiety disorders.
Cross-sectional data are from the Netherlands Study of Depression and Anxiety including participants (n = 2980) with and without depressive and anxiety disorders in the past year (based on DSM-based psychiatric interviews). We also determined symptom severity of depression (Inventory of Depression Symptomatology), anxiety (Beck Anxiety Inventory) and fear (Fear Questionnaire). Neighbourhood characteristics comprised socioeconomic factors (socioeconomic status, home value, number of social security beneficiaries and percentage of immigrants), physical factors (air pollution, traffic noise and availability of green space and water) and social factors (social cohesion and safety). Multilevel regression analyses were performed with the municipality as the second level while adjusting for individual sociodemographic variables and household income.
Not urbanization grade, but rather neighbourhood socioecononomic factors (low socioeconomic status, more social security beneficiaries and more immigrants), physical factors (high levels of traffic noise) and social factors (lower social cohesion and less safety) were associated with the presence of depressive and anxiety disorders. Most of these neighbourhood characteristics were also associated with increased depressive and anxiety symptoms severity.
These findings suggest that it is not population density in the neighbourhood, but rather the quality of socioeconomic, physical and social neighbourhood characteristics that is associated with the presence and severity of affective disorders.
The association between major depressive disorder (MDD) and obesity may stem from shared immunometabolic mechanisms particularly evident in MDD with atypical features, characterized by increased ...appetite and/or weight (A/W) during an active episode.
To determine whether subgroups of patients with MDD stratified according to the A/W criterion had a different degree of genetic overlap with obesity-related traits (body mass index BMI and levels of C-reactive protein CRP and leptin).
This multicenter study assembled genome-wide genotypic and phenotypic measures from 14 data sets of the Psychiatric Genomics Consortium. Data sets were drawn from case-control, cohort, and population-based studies, including 26 628 participants with established psychiatric diagnoses and genome-wide genotype data. Data on BMI were available for 15 237 participants. Data were retrieved and analyzed from September 28, 2015, through May 20, 2017.
Lifetime DSM-IV MDD was diagnosed using structured diagnostic instruments. Patients with MDD were stratified into subgroups according to change in the DSM-IV A/W symptoms as decreased or increased.
Data included 11 837 participants with MDD and 14 791 control individuals, for a total of 26 628 participants (59.1% female and 40.9% male). Among participants with MDD, 5347 (45.2%) were classified in the decreased A/W and 1871 (15.8%) in the increased A/W subgroups. Common genetic variants explained approximately 10% of the heritability in the 2 subgroups. The increased A/W subgroup showed a strong and positive genetic correlation (SE) with BMI (0.53 0.15; P = 6.3 × 10-4), whereas the decreased A/W subgroup showed an inverse correlation (-0.28 0.14; P = .06). Furthermore, the decreased A/W subgroup had a higher polygenic risk for increased BMI (odds ratio OR, 1.18; 95% CI, 1.12-1.25; P = 1.6 × 10-10) and levels of CRP (OR, 1.08; 95% CI, 1.02-1.13; P = 7.3 × 10-3) and leptin (OR, 1.09; 95% CI, 1.06-1.12; P = 1.7 × 10-3).
The phenotypic associations between atypical depressive symptoms and obesity-related traits may arise from shared pathophysiologic mechanisms in patients with MDD. Development of treatments effectively targeting immunometabolic dysregulations may benefit patients with depression and obesity, both syndromes with important disability.
We present the first large-scale methylome-wide association studies (MWAS) for major depressive disorder (MDD) to identify sites of potential importance for MDD etiology. Using a sequencing-based ...approach that provides near-complete coverage of all 28 million common CpGs in the human genome, we assay methylation in MDD cases and controls from both blood (N = 1132) and postmortem brain tissues (N = 61 samples from Brodmann Area 10, BA10). The MWAS for blood identified several loci with P ranging from 1.91 × 10
to 4.39 × 10
and a resampling approach showed that the cumulative association was significant (P = 4.03 × 10
) with the signal coming from the top 25,000 MWAS markers. Furthermore, a permutation-based analysis showed significant overlap (P = 5.4 × 10
) between the MWAS findings in blood and brain (BA10). This overlap was significantly enriched for a number of features including being in eQTLs in blood and the frontal cortex, CpG islands and shores, and exons. The overlapping sites were also enriched for active chromatin states in brain including genic enhancers and active transcription start sites. Furthermore, three loci located in GABBR2, RUFY3, and in an intergenic region on chromosome 2 replicated with the same direction of effect in the second brain tissue (BA25, N = 60) from the same individuals and in two independent brain collections (BA10, N = 81 and 64). GABBR2 inhibits neuronal activity through G protein-coupled second-messenger systems and RUFY3 is implicated in the establishment of neuronal polarity and axon elongation. In conclusion, we identified and replicated methylated loci associated with MDD that are involved in biological functions of likely importance to MDD etiology.
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