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Journal of Affective Disorders Jun 2024Heart rate variability (HRV) is often reduced in patients with major depressive disorder (MDD) and is linked to symptoms. However, prior studies have mainly focused on...
BACKGROUND
Heart rate variability (HRV) is often reduced in patients with major depressive disorder (MDD) and is linked to symptoms. However, prior studies have mainly focused on short-term HRV, with limited exploration of the 24-h HRV circadian rhythm, despite its ability to comprehensively capture overall HRV distribution and dynamic fluctuations. In this study, we investigated the circadian rhythms of 24-h HRV indices in patients with MDD and their associations with symptom severity.
METHODS
We recorded 24-h electrocardiograms in 73 patients with MDD (53 in major depressive episode and 20 in remission period) and 31 healthy controls. An extended cosine model was used to model the circadian rhythm of six HRV indices by five parameters: the mesor, amplitude, duty cycle, curve smoothness, and acrophase. Symptom severity was evaluated using the Hamilton Depression Scale and Hamilton Anxiety Scale.
RESULTS
Compared with the control group, patients with MDD had a significantly smaller SampEn mesor, higher HF duty cycle, and lower heart rate (HR) duty cycle. They also had a significantly higher curve smoothness for HR, RMSSD, and HF. The mesor for SampEn, along with the curve smoothness for HR and ln RMSSD, were associated with certain symptoms in patients with MDD.
LIMITATIONS
The cross-sectional design and psychiatric treatment of most patients with MDD limited our findings.
CONCLUSION
Patients with MDD exhibit abnormal HRV circadian rhythms that are associated with symptoms. Moreover, 24-h ECG monitoring may potentially serve as an adjunct value to objectively evaluate clinical symptoms in these patients.
PubMed: 38942206
DOI: 10.1016/j.jad.2024.06.102 -
Journal of Affective Disorders Jun 2024Post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) are psychiatric disorders that can present with overlapping symptoms and shared risk factors.... (Review)
Review
Similarities and differences between post-traumatic stress disorder and major depressive disorder: Evidence from task-evoked functional magnetic resonance imaging meta-analysis.
BACKGROUND
Post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) are psychiatric disorders that can present with overlapping symptoms and shared risk factors. However, the extent to which these disorders share common underlying neuropathological mechanisms remains unclear. To investigate the similarities and differences in task-evoked brain activation patterns between patients with PTSD and MDD.
METHODS
A coordinate-based meta-analysis was conducted across 35 PTSD studies (564 patients and 543 healthy controls) and 125 MDD studies (4049 patients and 4170 healthy controls) using anisotropic effect-size signed differential mapping software.
RESULTS
Both PTSD and MDD patients exhibited increased neural activation in the bilateral inferior frontal gyrus. However, PTSD patients showed increased neural activation in the right insula, left supplementary motor area extending to median cingulate gyrus and superior frontal gyrus (SFG), and left fusiform gyrus, and decreased neural activation in the right posterior cingulate gyrus, right middle temporal gyrus, right paracentral lobule, and right inferior parietal gyrus relative to MDD patients.
CONCLUSION
Our meta-analysis suggests that PTSD and MDD share some similar patterns of brain activation, but also have distinct neural signatures. These findings contribute to our understanding of the potential neuropathology underlying these disorders and may inform the development of more targeted and effective treatment and intervention strategies. Moreover, these results may provide useful neuroimaging targets for the differential diagnosis of MDD and PTSD.
PubMed: 38942203
DOI: 10.1016/j.jad.2024.06.095 -
Ageing Research Reviews Jun 2024Although numerous studies have investigated modifiable risk factors for mild cognitive impairment (MCI) among community-dwelling seniors, no meta-analysis has summarized... (Review)
Review
Although numerous studies have investigated modifiable risk factors for mild cognitive impairment (MCI) among community-dwelling seniors, no meta-analysis has summarized these findings. Five databases were searched from January 1, 2000, to December 30, 2023. The protocol was registered with PROSPERO. Data were extracted and reported following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Relevant meta-analyses of modifiable risk factors were performed. The evidence of each factor was assessed by the GRADE for cohort studies. Of 16,651 citations, 87 studies involving 225,584 community-dwelling seniors were included. Fourteen meta-analyses involving 20 studies with 44,199 participants were performed. The analyses revealed low-to-moderate-quality evidence supporting that diabetes, 2 or more comorbidities, anxiety, apathy, depressive symptoms, and physical frailty were risk factors for incident MCI in older adults. Conversely, hypertension, agitation, and irritability might not be risk factors. Additionally, moderate-quality evidence supports the protective effect of engaging in cognitive-demanding activities on the onset of MCI. Collectively, this study constitutes the first extensive compilation of evidence regarding the various risk factors for the development of MCI in older adults. Our findings hold significant potential to guide the formulation of prevention and management strategies to either prevent or potentially reverse the onset of MCI.
PubMed: 38942197
DOI: 10.1016/j.arr.2024.102350 -
Regulatory Toxicology and Pharmacology... Jun 2024Depressive disorders are one of the most common mental disorders globally and progress in treating these disorders has been hampered, in part, by a lack of suitable... (Review)
Review
Depressive disorders are one of the most common mental disorders globally and progress in treating these disorders has been hampered, in part, by a lack of suitable nonclinical efficacy tests. Two common tests used in nonclinical efficacy studies of antidepressants-the forced swim test (FST) and tail suspension test (TST)-have come under criticism in recent years for their inconsistency and lack of validity, yet they continue to be used in the pharmaceutical industry. In this review, we provide a rationale for why international pharmaceutical regulatory and guidance agencies should begin issuing direction on methods for non-clinical efficacy testing that traditionally use the FST and TST, particularly considering that some regulators, such as those in the U.S. and E.U., allow the authorization of clinical trials to proceed without requiring tests in animals. The area of antidepressant drug discovery represents an important opportunity for reducing the attrition of psychiatric drugs, harmonizing regulatory requirements, and reducing animal use. Specific recommendations for the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) have been provided.
PubMed: 38942190
DOI: 10.1016/j.yrtph.2024.105666 -
Journal of Clinical Epidemiology Jun 2024To use individual participant data meta-analysis (IPDMA) to estimate the minimal detectable change (MDC) of the Geriatric Depression Scale-15 (GDS-15) and to examine...
OBJECTIVE
To use individual participant data meta-analysis (IPDMA) to estimate the minimal detectable change (MDC) of the Geriatric Depression Scale-15 (GDS-15) and to examine whether MDC may differ based on participant characteristics and study-level variables.
STUDY DESIGN AND SETTING
This was a secondary analysis of data from an IPDMA on the depression screening accuracy of the GDS. Datasets from studies published in any language were eligible for the present study if they included GDS-15 scores for participants aged 60 or older. MDC of the GDS-15 was estimated via random-effects meta-analysis using 2.77 (MDC95) and 1.41 (MDC67) standard errors of measurement (SEM). Subgroup analyses were used to evaluate differences in MDC by participant age and sex. Meta-regression was conducted to assess for differences based on study-level variables, including mean age, proportion male, proportion with major depression, and recruitment setting.
RESULTS
5,876 participants (mean age 76 years, 40% male, 11% with major depression) from 21 studies were included. The MDC95 was 3.81 points (95% confidence interval [CI] 3.59, 4.04), and MDC67 was 1.95 (95% CI 1.83, 2.03). The difference in MDC95 was 0.26 points (95% CI 0.04, 0.48) between ≥ 80-year-olds and < 80-year-olds; MDC95 was similar for females and males (0.05, 95% CI -0.12, 0.22). The MDC95 increased by 0.29 points (95% CI 0.17, 0.41) per 10% increase in proportion of participants with major depression; mean age had a small association (0.04 points, 95% CI 0.00 to 0.09) with MDC95, but sex and recruitment setting were not significantly associated.
CONCLUSIONS
The MDC95 was 3.81 points and MDC67 was 1.95 points. MDC95 increased with the proportion of participants with major depression. Results can be used to evaluate individual changes in depression symptoms and as a threshold for assessing minimal clinical important difference estimates.
PubMed: 38942179
DOI: 10.1016/j.jclinepi.2024.111443 -
Biological Psychiatry. Cognitive... Jun 2024The mechanisms linking neural and behavioral indices of reduced reward sensitivity in depression, particularly in children, remain unclear. Reward positivity (RewP), a...
BACKGROUND
The mechanisms linking neural and behavioral indices of reduced reward sensitivity in depression, particularly in children, remain unclear. Reward positivity (RewP), a neural index of reward processing, has been consistently associated with depression. Separately, recent studies using the drift-diffusion model (DDM) on behavioral data have delineated computational indices of reward sensitivity. Therefore, the present study examined whether RewP is a neural mediator of DDM-based indices of reward processing in predicting pediatric depression across varying levels of symptom severity.
METHODS
A community sample of 166 girls, aged 8 to 14 years, completed two tasks. The first was a reward guessing task from which RewP was computed using electroencephalography; the second was a probabilistic reward-based decision-making task. On this second task, DDM analysis was applied to behavioral data to quantify the efficiency of accumulating reward-related evidence (drift rate) and potential baseline bias (starting point) towards the differently rewarded choices. Depression severity was measured using the self-report Children's Depression Inventory (CDI).
RESULTS
RewP was correlated with drift rate, but not starting point bias, towards the more rewarded choice. Furthermore, RewP completely mediated the association between a slower drift rate towards the more rewarded option and higher depression symptom severity.
CONCLUSION
Our findings suggest that reduced neural sensitivity to reward feedback might be a neural mechanism underscoring behavioral insensitivity to reward in children and adolescents with higher depression symptom severity, offering novel insights into the relationship between neural and computational indices of reward processing in this context.
PubMed: 38942146
DOI: 10.1016/j.bpsc.2024.06.007 -
Preventive Medicine Jun 2024Pregnant persons with opioid use disorder (OUD) face a multitude of comorbid conditions that may increase the risk of adverse drug and health outcomes. This study...
INTRODUCTION
Pregnant persons with opioid use disorder (OUD) face a multitude of comorbid conditions that may increase the risk of adverse drug and health outcomes. This study characterizes typologies of comorbidities among pregnant persons with OUD and assesses the associations of these typologies with hospitalizations in the first year postpartum.
METHODS
A cohort of pregnant persons with OUD at delivery in 2018 were identified in a Pennsylvania statewide hospital dataset (n = 2055). Latent class analysis assessed 12 comorbid conditions including substance use disorders (SUDs), mental health conditions, and infections. Multivariable logistic regressions examined the association between comorbidity classes and hospitalizations (all-cause, OUD-specific, SUD-related, mental health-related) during early (0-42 days) and late (43-365 days) postpartum.
RESULTS
A three-class model best fit the data. Classes included low comorbidities (56.9% of sample; low prevalence of co-occurring conditions), moderate polysubstance/depression (18.4%; some SUDs, all with depression), and high polysubstance/bipolar disorder (24.7%; highest probabilities of SUDs and bipolar disorder). Overall, 14% had at least one postpartum hospitalization. From 0 to 42 days postpartum, the moderate polysubstance/depression and high polysubstance/bipolar disorder classes had higher odds of all-cause and mental health-related hospitalization, compared to the low comorbidities class. From 43 to 365 days postpartum, the high polysubstance/bipolar disorder class had higher odds of all-cause hospitalizations, while both the high polysubstance/depression and moderate polysubstance/bipolar disorder classes had higher odds of SUD-related and mental health-related hospitalizations compared to the low comorbidities class.
CONCLUSIONS
Findings highlight the need for long-term, multidisciplinary healthcare delivery interventions to address comorbidities and prevent adverse postpartum outcomes.
PubMed: 38942123
DOI: 10.1016/j.ypmed.2024.108057 -
Biochemical Pharmacology Jun 2024GPR56, also known as GPR56/ADGRG1, is a member of the ADGRG subgroup belonging to adhesion G protein-coupled receptors (aGPCRs). aGPCRs are the second largest subfamily... (Review)
Review
GPR56, also known as GPR56/ADGRG1, is a member of the ADGRG subgroup belonging to adhesion G protein-coupled receptors (aGPCRs). aGPCRs are the second largest subfamily of the GPCR superfamily, which is the largest family of membrane protein receptors in the human genome. Studies in recent years have demonstrated that GPR56 is integral to the normal development of the brain and functions as an important player in cortical development, suggesting that GPR56 is involved in many physiological processes. Indeed, aberrant expression of GPR56 has been implicated in multiple neurological and psychiatric disorders, including bilateral frontoparietal polymicrogyria (BFPP), depression and epilepsy. In a recent study, it was found that upregulated expression of GPR56 reduced depressive-like behaviours in an animal model of depression, indicating that GPR56 plays an important role in the antidepressant response. Given the link of GPR56 with the antidepressant response, the function of GPR56 has become a focus of research. Although GPR56 may be a potential target for the development of antidepressants, the underlying molecular mechanisms remain largely unknown. Therefore in this review, we will summarize the latest findings of GPR56 function in neurological and psychiatric disorders (depression, epilepsy, autism, and BFPP) and emphasize the mechanisms of GPR56 in activation and signalling in those conditions. After reviewing several studies, attributing to its significant biological functions and exceptionally long extracellular N-terminus that interacts with multiple ligands, we draw a conclusion that GPR56 may serve as an important drug target for neuropsychological diseases.
PubMed: 38942087
DOI: 10.1016/j.bcp.2024.116395 -
Behavioural Brain Research Jun 2024Stressful life event is closely associated with depression, thus strategies that blunt or prevent the negative effect stress on the brain might benefits for the...
Stressful life event is closely associated with depression, thus strategies that blunt or prevent the negative effect stress on the brain might benefits for the treatment of depression. Although previous study showed the role of protein kinase R (PKR)-like ER kinase (PERK) in inflammation related depression, its involvement in the neuropathology of chronic stress induced depression is still unknown. We tried to explore whether block the PERK pathway would alleviate the animals' depression-like behavior induced by chronic restraint stress (CRS) and investigate the underlying mechanism. The CRS-exposed mice exhibited depression-like behavior, including anhedonia in the sucrose preference test (SPT), and increased immobility time in tail suspension test (TST) and forced swim test (FST). ISRIB administration for 2 weeks significantly improved the depression-like behavior in male mice exposed to CRS,which was manifested by markedly increasing the sucrose preference and reducing the immobility time in the FST and TST. However, we observed that exposure to the same dose of ISRIB in CRS female mice only showed improved anhedonia-like deficits,leaving un-altered improvement in the FST and TST. Mechanically, we found thatISRIB reversed the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, indicatingby decreased levels of serum corticosterone, reduced hippocampal glucocorticoidreceptor (GR) expression and expression of FosB in hypothalamic paraventricularnucleus (PVN), which was accompanied by preserved hippocampal neurogenesis. Thepresent findings further expand the potential role of ER stress in depression andprovide important details for a therapeutic path forward for PERK inhibitors in mood disorders.
PubMed: 38942086
DOI: 10.1016/j.bbr.2024.115122 -
Cell Jun 2024A number of species have recently recovered from near-extinction. Although these species have avoided the immediate extinction threat, their long-term viability remains...
A number of species have recently recovered from near-extinction. Although these species have avoided the immediate extinction threat, their long-term viability remains precarious due to the potential genetic consequences of population declines, which are poorly understood on a timescale beyond a few generations. Woolly mammoths (Mammuthus primigenius) became isolated on Wrangel Island around 10,000 years ago and persisted for over 200 generations before becoming extinct around 4,000 years ago. To study the evolutionary processes leading up to the mammoths' extinction, we analyzed 21 Siberian woolly mammoth genomes. Our results show that the population recovered quickly from a severe bottleneck and remained demographically stable during the ensuing six millennia. We find that mildly deleterious mutations gradually accumulated, whereas highly deleterious mutations were purged, suggesting ongoing inbreeding depression that lasted for hundreds of generations. The time-lag between demographic and genetic recovery has wide-ranging implications for conservation management of recently bottlenecked populations.
PubMed: 38942016
DOI: 10.1016/j.cell.2024.05.033