Abstract Background Low serum 25-hydroxyvitamin D (25-OH-D) has recently been linked to cardiovascular diseases. This review summarizes evidence from prospective studies evaluating the prognostic ...value of 25-OH-D for cardiovascular disease incidence and mortality. Method A systematic literature search in EMBASE and Pubmed-Medline databases was performed until November 2009. Prospective studies published in English were selected reporting estimates for the association of 25-OH-D with primary or secondary cardiovascular event incidence or mortality in the general population or subjects with prevalent cardiovascular disease. Pooled risk estimators were derived by meta-analysis using a random effects model approach. Results Four incidence and five independent mortality studies were included. Two incidence and three mortality studies reported a two- to five-fold risk increase for both outcomes in subjects with lower 25-OH-D, while the others did not detect a significant association. Meta-analysis supported the existence of an inverse association. Conclusion Data from prospective investigations suggest an inverse association between 25-OH-D and cardiovascular risk. However, given the heterogeneity and small number of longitudinal studies, more research is needed to corroborate a potential prognostic value of 25-OH-D for cardiovascular disease incidence and mortality.
A major research finding in the field of Biological Psychiatry is that symptom-based categories of mental disorders map poorly onto dysfunctions in brain circuits or neurobiological pathways. Many of ...the identified (neuro) biological dysfunctions are "transdiagnostic", meaning that they do not reflect diagnostic boundaries but are shared by different ICD/DSM diagnoses. The compromised biological validity of the current classification system for mental disorders impedes rather than supports the development of treatments that not only target symptoms but also the underlying pathophysiological mechanisms. The Biological Classification of Mental Disorders (BeCOME) study aims to identify biology-based classes of mental disorders that improve the translation of novel biomedical findings into tailored clinical applications.
BeCOME intends to include at least 1000 individuals with a broad spectrum of affective, anxiety and stress-related mental disorders as well as 500 individuals unaffected by mental disorders. After a screening visit, all participants undergo in-depth phenotyping procedures and omics assessments on two consecutive days. Several validated paradigms (e.g., fear conditioning, reward anticipation, imaging stress test, social reward learning task) are applied to stimulate a response in a basic system of human functioning (e.g., acute threat response, reward processing, stress response or social reward learning) that plays a key role in the development of affective, anxiety and stress-related mental disorders. The response to this stimulation is then read out across multiple levels. Assessments comprise genetic, molecular, cellular, physiological, neuroimaging, neurocognitive, psychophysiological and psychometric measurements. The multilevel information collected in BeCOME will be used to identify data-driven biologically-informed categories of mental disorders using cluster analytical techniques.
The novelty of BeCOME lies in the dynamic in-depth phenotyping and omics characterization of individuals with mental disorders from the depression and anxiety spectrum of varying severity. We believe that such biology-based subclasses of mental disorders will serve as better treatment targets than purely symptom-based disease entities, and help in tailoring the right treatment to the individual patient suffering from a mental disorder. BeCOME has the potential to contribute to a novel taxonomy of mental disorders that integrates the underlying pathomechanisms into diagnoses.
Retrospectively registered on June 12, 2019 on ClinicalTrials.gov (TRN: NCT03984084).
Electroconvulsive therapy (ECT) is commonly used to treat treatment-resistant depression (TRD). However, our knowledge of the ECT-induced molecular mechanisms causing clinical improvement is limited. ...To address this issue, we developed the single-center, prospective observational DetECT study (“Multimodal Biomarkers of ECT in TRD”; registered 18/07/2022,
www.clinicalTrials.gov
, NCT05463562). Its objective is to identify molecular, psychological, socioeconomic, and clinical biomarkers of ECT response in TRD. We aim to recruit
n
= 134 patients in 3 years. Over the course of 12 biweekly ECT sessions (± 7 weeks), participant blood is collected before and 1 h after the first and seventh ECT and within 1 week after the twelfth session. In pilot subjects (first
n
= 10), additional blood draws are performed 3 and 6 h after the first ECT session to determine the optimal post-ECT blood draw interval. In blood samples, multiomic analyses are performed focusing on genotyping, epigenetics, RNA sequencing, neuron-derived exosomes, purines, and immunometabolics. To determine clinical response and side effects, participants are asked weekly to complete four standardized self-rating questionnaires on depressive and somatic symptoms. Additionally, clinician ratings are obtained three times (weeks 1, 4, and 7) within structured clinical interviews. Medical and sociodemographic data are extracted from patient records. The multimodal data collected are used to perform the conventional statistics as well as mixed linear modeling to identify clusters that link biobehavioural measures to ECT response. The DetECT study can provide important insight into the complex mechanisms of ECT in TRD and a step toward biologically informed and data-driven-based ECT biomarkers.
Maladaptive stress responses are important risk factors in the etiology of mood and anxiety disorders, but exact pathomechanisms remain to be understood. Mapping individual differences of acute ...stress-induced neurophysiological changes, especially on the level of neural activation and functional connectivity (FC), could provide important insights in how variation in the individual stress response is linked to disease risk.
Using an established psychosocial stress task flanked by two resting states, we measured subjective, physiological, and brain responses to acute stress and recovery in 217 participants with and without mood and anxiety disorders. To estimate blockwise changes in stress-induced activation and FC, we used hierarchical mixed-effects models based on denoised time series within predefined stress-related regions. We predicted inter- and intraindividual differences in stress phases (anticipation vs. stress vs. recovery) and transdiagnostic dimensions of stress reactivity using elastic net and support vector machines.
We identified four subnetworks showing distinct changes in FC over time. FC but not activation trajectories predicted the stress phase (accuracy = 70%, pperm < .001) and increases in heart rate (R2 = 0.075, pperm < .001). Critically, individual spatiotemporal trajectories of changes across networks also predicted negative affectivity (ΔR2 = 0.075, pperm = .030) but not the presence or absence of a mood and anxiety disorder.
Spatiotemporal dynamics of brain network reconfiguration induced by stress reflect individual differences in the psychopathology dimension of negative affectivity. These results support the idea that vulnerability for mood and anxiety disorders can be conceptualized best at the level of network dynamics, which may pave the way for improved prediction of individual risk.
Major depressive disorder (MDD) has been related to abnormal amygdala activity during emotional face processing. However, a recent large-scale study (
n
= 28,638) found no such correlation, which is ...probably due to the low precision of fMRI measurements. To address this issue, we used simultaneous fMRI and eye-tracking measurements during a commonly employed emotional face recognition task. Eye-tracking provide high-precision data, which can be used to enrich and potentially stabilize fMRI readouts. With the behavioral response, we additionally divided the active task period into a task-related and a free-viewing phase to explore the gaze patterns of MDD patients and healthy controls (HC) and compare their respective neural correlates. Our analysis showed that a mood-congruency attentional bias could be detected in MDD compared to healthy controls during the free-viewing phase but without parallel amygdala disruption. Moreover, the neural correlates of gaze patterns reflected more prefrontal fMRI activity in the free-viewing than the task-related phase. Taken together, spontaneous emotional processing in free viewing might lead to a more pronounced mood-congruency bias in MDD, which indicates that combined fMRI with eye-tracking measurement could be beneficial for our understanding of the underlying psychopathology of MDD in different emotional processing phases.
Trial Registration
: The BeCOME study is registered on ClinicalTrials (gov: NCT03984084) by the Max Planck Institute of Psychiatry in Munich, Germany.
Circulating nonesterified or free fatty acids (FFAs) may contribute to the development of cardiovascular pathology and correlate with ischemia in acute cardiovascular conditions. The aim of this ...study was to assess whether serum levels of FFAs are associated with long-term prognosis in subjects with stable coronary heart disease. This observational prospective cohort study included 1,206 participants in 3-weeks inpatient rehabilitation programs after acute myocardial infarction, coronary syndromes, or coronary intervention at 2 rehabilitation clinics in Germany (1999 to 2000). Eight-year prognosis (time to a secondary fatal or nonfatal cardiovascular disease event including myocardial infarction and stroke n = 153 and time to death from any cause n = 124) was examined according to FFA quartiles and in spline regression. FFAs were correlated with established serum markers of cardiovascular risk and strongly related to secondary cardiovascular events and all-cause mortality in age- and gender-adjusted analysis. When additionally controlling for multiple established risk factors and risk markers, the hazard ratio in the fourth versus first quartile was 1.34 (95% confidence interval 0.79 to 2.24) for secondary cardiovascular events and 1.09 (95% confidence interval 0.62 to 1.91) for all-cause mortality. Dose-response modeling suggested that very high FFAs might predict an increased risk for mortality (hazard ratio 1.98, 95% confidence interval 0.98 to 4.02, for 95th percentile vs first quartile). In conclusion, FFAs are closely correlated with cardiovascular risk markers, and in particular, very high FFA might identify patients with stable coronary heart disease with worse prognoses.
Abstract
Overweight and obesity are associated with altered stress reactivity and increased inflammation. However, it is not known whether stress-induced changes in brain function scale with BMI and ...if such associations are driven by peripheral cytokines. Here, we investigate multimodal stress responses in a large transdiagnostic sample using predictive modeling based on spatio-temporal profiles of stress-induced changes in activation and functional connectivity. BMI is associated with increased brain responses as well as greater negative affect after stress and individual response profiles are associated with BMI in females (
p
perm
< 0.001), but not males. Although stress-induced changes reflecting BMI are associated with baseline cortisol, there is no robust association with peripheral cytokines. To conclude, alterations in body weight and energy metabolism might scale acute brain responses to stress more strongly in females compared to males, echoing observational studies. Our findings highlight sex-dependent associations of stress with differences in endocrine markers, largely independent of peripheral inflammation.
Fear conditioning and extinction serve as a dominant model for the development and maintenance of pathological anxiety, particularly for phasic fear to specific stimuli or situations. The validity of ...this model would be supported by differences in the physiological or subjective fear response between patients with fear-related disorders and healthy controls, whereas the model's validity would be questioned by a lack of such differences.
We derived pupillometry, skin conductance response and startle electromyography as well as unconditioned stimulus expectancy in a two-day fear acquisition, immediate extinction and recall task and compared an unmedicated group of patients (n = 73) with phobias or panic disorder and a group of patients with posttraumatic stress disorder (PTSD, n = 21) to a group of carefully screened healthy controls (n = 35).
Bayesian statistics showed no convincing evidence for a difference in physiological and subjective responses between the groups during fear acquisition, extinction learning or recall. Only the PTSD subgroup had altered startle reactions during extinction learning.
Our data do not provide evidence for general differences in associative fear or extinction learning in fear-related pathologies and thereby question the diagnostic validity of the associative fear learning model of these disorders.
•Patients with fear disorders, PTSD, and controls were exposed to a fear acquisition, immediate extinction and recall task.•No robust differences in associative fear acquisition, extinction and recall between groups were detected.•There was anecdotal evidence for altered startle responses during extinction in patients with PTSD.•Results question the diagnostic validity of abnormalities in fear learning in patients with fear-related disorders.
Recent longitudinal studies have suggested an association of high serum parathyroid hormone levels (PTH) with elevated cardiovascular risk in the general population. This study presents analyses of ...the prognostic value of baseline PTH for subsequent cardiovascular events and all-cause mortality in a high-risk population with stable coronary heart disease.
Based on measurements of PTH levels in 1133 patients recruited at two German rehabilitation clinics and followed over 8 years, multivariate Cox regression analysis was performed to estimate the risk of secondary cardiovascular events (including myocardial infarction, stroke and death due to cardiovascular diseases) and all-cause-mortality according to PTH quartiles (Q1-Q4) and continuous PTH concentrations.
During follow-up, 153 cardiovascular events and 124 deaths occurred. Age and sex-adjusted Cox regression analysis yielded statistically significant positive associations of PTH with both cardiovascular event incidence and all-cause mortality (HR (95% CI) per SD increase of PTH: 1.35 (1.21-1.51) and 1.25 (1.11-1.42), respectively). Associations remained essentially unchanged after additional adjustment for multiple cardiovascular risk factors. More detailed dose-response analyses showed strong risk elevation for above-normal levels of PTH (> 95th percentile), with essentially no association at lower levels.
The results of this first detailed study in a cohort of patients with stable coronary heart disease suggest an independent predictive value of above-normal PTH for the prognosis in patients with stable coronary heart disease.
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