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Biomedicines Jun 2024Patients with major depressive disorder (MDD) have an increased risk for cardiac events. This is partly attributed to a disbalance of the autonomic nervous system (ANS)...
Patients with major depressive disorder (MDD) have an increased risk for cardiac events. This is partly attributed to a disbalance of the autonomic nervous system (ANS) indicated by a reduced vagal tone and a (relative) sympathetic hyperactivity. However, in most studies, heart rate variability (HRV) was only examined while resting. So far, it remains unclear whether the dysbalance of the ANS in patients with MDD is restricted to resting or whether it is also evident during sympathetic and parasympathetic activation. The aim of this study was to compare the responses of the ANS to challenges that stimulated the sympathetic and, respectively, the parasympathetic nervous systems in patients with MDD. Forty-six patients with MDD (female 27 (58.7%), mean age 44 ± 17 years) and 46 healthy controls (female 26 (56.5%), mean age 44 ± 20 years) underwent measurement of time- and frequency-dependent domains of HRV at rest, while standing (sympathetic challenge), and during slow-paced breathing (SPB, vagal, i.e., parasympathetic challenge). Patients with MDD showed a higher heart rate, a reduced HRV, and a diminished vagal tone during resting, standing, and SPB compared to controls. Patients with MDD and controls responded similarly to sympathetic and vagal activation. However, the extent of modulation of the ANS was impaired in patients with MDD, who showed a reduced decrease in the vagal tone but also a reduced increase in sympathetic activity when switching from resting to standing. Assessing changes in the ANS during sympathetic and vagal activation via respective challenges might serve as a future biomarker and help to allocate patients with MDD to therapies like HRV biofeedback and psychotherapy that were recently found to modulate the vagal tone.
PubMed: 38927475
DOI: 10.3390/biomedicines12061268 -
Biomedicines Jun 2024Fibromyalgia (FM) is a chronic pain disorder and is associated with disability, and high levels of pain and suffering. FM is known to co-occur with obesity and...
Correlation of Psychological Factors, Obesity, Serum Cortisol, and C-Reactive Protein in Patients with Fibromyalgia Diagnosed with Obstructive Sleep Apnea and Other Comorbidities.
BACKGROUND
Fibromyalgia (FM) is a chronic pain disorder and is associated with disability, and high levels of pain and suffering. FM is known to co-occur with obesity and obstructive sleep apnea (OSA). Individuals with FM often experience symptoms of pain, depression and anxiety, sleep disturbances, and fatigue. These symptoms may be exacerbated by OSA and contribute to the symptoms' severity in FM. Obesity is a common comorbidity in OSA patients, and as FM and OSA are related in some patients, obesity also may contribute to FM symptom severity. For healthcare providers to effectively manage FM patients, a better understanding of the co-occurrence between these FM comorbidities and psychological factors is needed.
METHODS
This study was approved by IRB and conducted using a retrospective EPIC chart review. To identify FM, the following ICD-9 codes were used: (729.1) and ICD-10 (M79.7) codes. To identify patients with OSA, the following ICD-9 codes were used: (327.23) and ICD-10 (G47.33). Body Mass Index (BMI), the total number of medical diagnoses, and psychiatric conditions were documented for each patient. The prevalence of psychiatric conditions including depression and anxiety was compared between patients with and without obesity (BMI > 30), and patients with fewer than 25 medical diagnoses and those with 25 or more diagnoses. A chart review was conducted to identify patients with fibromyalgia with prior serum cortisol testing within the last ten years. Cortisol levels were compared and patients were divided into six groups: 1. FM without identified psychiatric conditions; 2. FM with psychiatric diagnosis of adjustment disorders and insomnia; 3. FM with psychiatric diagnosis of depressive disorders; 4. FM with psychiatric diagnosis of bipolar disorders; 5. FM with psychiatric diagnosis of mixed anxiety and depression; 6. FM with psychiatric diagnosis of anxiety disorders. Available C-reactive protein (CRP) values were gathered.
RESULTS
The total FM and OSA population was N = 331. The mean age of the patient population was 63.49 years old, with 297 being female. The diagnoses mean was 31.79 ± 17.25 and the mean total psychiatric diagnoses was 2.80 ± 1.66. The mean BMI was 36.69 ± 8.86, with obesity present in 77.95% of the patients. A total of 66.99% of patients had comorbid anxiety and depression with 25 or more medical problems vs. 33.01% of patients who had fewer than 25 medical problems (odds ratio = 1.50). Patients with a BMI < 30 (N = 71) had rates of anxiety and depression at 64.79% and a mean total of 2.79 ± 1.66 psychiatric diagnoses, whereas patients with a BMI > 30 (N = 258) had rates of anxiety and depression at 61.63% (odds ratio = 1.28) and a mean total of 2.80 ± 1.66 psychiatric diagnoses. The most common other psychiatric conditions among FM/OSA patients included hypersomnia and substance use disorders. Cortisol data: Available cortisol results: FM n = 64, female: 59, male: 5, mean age: 63, average BMI: 38.8. The averages for serum cortisol alone for groups 1-6, respectively, are 9.06, 5.49, 13.00, 14.17, 12.25, and 16.03 μg/dL. These results indicate a relatively upward cortisol serum value by the addition of several psychiatric conditions, with the most notable being anxiety for patients with FM. CRP values were available for 53 patients with an average CRP of 4.14.
DISCUSSION
Higher rates of anxiety and depression were present in FM patients with 25 or more diagnoses. The odds ratios indicate that a patient with 25 or more medical problems was 1.5 times more likely to have anxiety and depression than those with fewer diagnoses. Additionally, those with a BMI > 30 were 1.3 times more likely to have anxiety and depression than those with a normal BMI.
CONCLUSION
addressing psychological factors in FM and OSA is important as high healthcare utilization is common in patients with FM and OSA.
PubMed: 38927472
DOI: 10.3390/biomedicines12061265 -
Biomedicines Jun 2024Depression is a common mental illness of great concern. Current therapy for depression is only suitable for 80% of patients and is often associated with unwanted side... (Review)
Review
Depression is a common mental illness of great concern. Current therapy for depression is only suitable for 80% of patients and is often associated with unwanted side effects. In this regard, the search for and development of new antidepressant agents remains an urgent task. In this review, we discuss the current available evidence indicating that G protein-coupled trace amine-associated receptors (TAARs) might represent new targets for depression treatment. The most frequently studied receptor TAAR1 has already been investigated in the treatment of schizophrenia, demonstrating antidepressant and anxiolytic properties. In fact, the TAAR1 agonist Ulotaront is currently undergoing phase 2/3 clinical trials testing its safety and efficacy in the treatment of major depressive disorder and generalized anxiety disorder. Other members of the TAAR family (TAAR2, TAAR5, TAAR6, TAAR8, and TAAR9) are not only involved in the innate olfaction of volatile amines, but are also expressed in the limbic brain areas. Furthermore, animal studies have shown that TAAR2 and TAAR5 regulate emotional behaviors and thus may hold promise as potential antidepressant targets. Of particular interest is their connection with the dopamine and serotonin systems of the brain and their involvement in the regulation of adult neurogenesis, known to be affected by the antidepressant drugs currently in use. Further non-clinical and clinical studies are necessary to validate TAAR1 (and potentially other TAARs) as novel therapeutic targets for the treatment of depression.
PubMed: 38927470
DOI: 10.3390/biomedicines12061263 -
Biomedicines May 2024Major depressive disorder (MDD) increases the risk of type 2 diabetes (T2D) by 60% in untreated patients, and hypercortisolism is common in MDD as well as in some... (Review)
Review
Major depressive disorder (MDD) increases the risk of type 2 diabetes (T2D) by 60% in untreated patients, and hypercortisolism is common in MDD as well as in some patients with T2D. Patients with MDD, despite hypercortisolism, show inappropriately normal levels of corticotropin-releasing hormone (CRH) and plasma adrenocorticotropin (ACTH) in the cerebrospinal fluid, which might implicate impaired negative feedback. Also, a positive feedback loop of the CRH-norepinephrine (NE)-CRH system may be involved in the hypercortisolism of MDD and T2D. Dysfunctional CRH receptor 1 (CRHR1) and CRH receptor 2 (CRHR2), both of which are involved in glucose regulation, may explain hypercortisolism in MDD and T2D, at least in a subgroup of patients. CRHR1 increases glucose-stimulated insulin secretion. Dysfunctional variants can cause hypercortisolism, leading to serotonin dysfunction and depression, which can contribute to hyperglycemia, insulin resistance, and increased visceral fat, all of which are characteristics of T2D. CRHR2 is implicated in glucose homeostasis through the regulation of insulin secretion and gastrointestinal functions, and it stimulates insulin sensitivity at the muscular level. A few studies show a correlation of the gene with depressive disorders. Based on our own research, we have found a linkage and association (i.e., linkage disequilibrium [LD]) of the genes and with MDD and T2D in families with T2D. The correlation of and with MDD appears stronger than that with T2D, and per our hypothesis, MDD may precede the onset of T2D. According to the findings of our analysis, and variants could modify the response to prolonged chronic stress and contribute to high levels of cortisol, increasing the risk of developing MDD, T2D, and the comorbidity MDD-T2D. We report here the potential links of the CRH system, NE, and their roles in MDD and T2D.
PubMed: 38927393
DOI: 10.3390/biomedicines12061187 -
Biomedicines May 2024The escalating rates of morbidity and mortality associated with opioid use disorder (OUD) have spurred a critical need for improved treatment outcomes. This study aimed...
The escalating rates of morbidity and mortality associated with opioid use disorder (OUD) have spurred a critical need for improved treatment outcomes. This study aimed to investigate the impact of prolonged exposure to Fentanyl, a potent opioid, on behavior, biochemical markers, oxidative stress, and the composition of the gut microbiome. Additionally, we sought to explore the therapeutic potential of in mitigating the adverse effects of Fentanyl withdrawal. The study unveiled that chronic Fentanyl administration induced a withdrawal syndrome characterized by elevated cortisol levels (12.09 mg/mL, compared to 6.3 mg/mL for the control group). This was accompanied by heightened anxiety, indicated by a reduction in time spent and entries made into the open arm in the Elevated Plus Maze Test, as well as depressive-like behaviors, manifested through increased immobility time in the Forced Swim Test. Additionally, Fentanyl exposure correlated with decreased gut microbiome density and diversity, coupled with heightened oxidative stress levels, evidenced by elevated malondialdehyde (MDA) and reduced levels of catalase (CAT) and superoxide dismutase (SOD). However, both post- and co-administration of exhibited substantial improvements in these adverse effects, effectively alleviating symptoms associated with OUD withdrawal syndrome and eliciting positive influences on gut microbiota. In conclusion, this research underscores the therapeutic potential of in managing Fentanyl withdrawal symptoms. The findings indicate promising effects in alleviating behavioral impairments, reducing stress, restoring gut microbiota, and mitigating oxidative stress, offering valuable insights for addressing the challenges of OUD treatment.
PubMed: 38927359
DOI: 10.3390/biomedicines12061152 -
Scientific Data Jun 2024Major depressive disorder (MDD) and substance-use disorders (SUDs) often lead to premature aging, increasing vulnerability to cognitive decline and other forms of...
Major depressive disorder (MDD) and substance-use disorders (SUDs) often lead to premature aging, increasing vulnerability to cognitive decline and other forms of dementia. This study utilized advanced systems bioinformatics to identify aging "signatures" in MDD and SUDs and evaluated the potential for known lifespan-extending drugs to target and reverse these signatures. The results suggest that inhibiting the transcriptional activation of FOS gene family members holds promise in mitigating premature aging in MDD and SUDs. Conversely, antidepressant drugs activating the PI3K/Akt/mTOR pathway, a common mechanism in rapid-acting antidepressants, may accelerate aging in MDD patients, making them unsuitable for those with comorbid aging-related conditions like dementia and Alzheimer's disease. Additionally, this innovative approach identifies potential anti-aging interventions for MDD patients, such as Deferoxamine, Resveratrol, Estradiol valerate, and natural compounds like zinc acetate, genistein, and ascorbic acid, regardless of comorbid anxiety disorders. These findings illuminate the premature aging effects of MDD and SUDs and offer insights into treatment strategies for patients with comorbid aging-related conditions, including dementia and Alzheimer's disease.
Topics: Humans; Depressive Disorder, Major; Substance-Related Disorders; Aging, Premature; Antidepressive Agents
PubMed: 38926475
DOI: 10.1038/s41597-024-03538-z -
Scientific Reports Jun 2024Network analysis provides an innovative approach to examining symptom-to-symptom interactions in mental health, and adverse external conditions may change the network... (Comparative Study)
Comparative Study
Network analysis provides an innovative approach to examining symptom-to-symptom interactions in mental health, and adverse external conditions may change the network structures. This study compared the networks of common risk factors and mental health problems (loneliness, depressive symptoms, and anxiety symptoms) in community-dwelling older people before and during COVID-19. Older adults (aged ≥ 60) at risk for depression were recruited through non-governmental organizations. Loneliness, depressive symptoms and anxiety symptoms were measured using the three-item Loneliness Scale (UCLA-3), nine-item Patient Health Questionnaire (PHQ-9), and seven-item Generalized Anxiety Disorder Scale (GAD-7), respectively. Data from 2549 (before) and 3506 (during COVID-19) respondents were included using propensity score matching. Being restless (GAD-7-item5) was most central, indicated by Expected Influence, in both pre and during COVID-19 networks despite low severity (mean score). The network during COVID-19 had higher global strength and edge variability than the pre-pandemic network, suggesting easier symptom spread and potentially more complex symptom presentation. In addition, feeling isolated from others (UCLA-3-item3) had stronger connections with feeling worthless/guilty (PHQ-9-item6) and anticipatory anxiety (GAD-7-item7) during COVID-19 than before. These findings may enhance our knowledge of the symptom structure of common mental health problems and the impacts of the pandemic. Targeting central symptoms may offer novel preventive strategies for older people.
Topics: Humans; COVID-19; Aged; Loneliness; Male; Female; Depression; Independent Living; Anxiety; Aged, 80 and over; SARS-CoV-2; Risk Factors; Middle Aged; Mental Health; Surveys and Questionnaires
PubMed: 38926445
DOI: 10.1038/s41598-024-65533-z -
BMJ Open Jun 2024The prevalence of major depressive disorder (MDD) is on the rise globally, and the use of antidepressant medications for its treatment does not usually result in full... (Randomized Controlled Trial)
Randomized Controlled Trial
Study protocol on the efficacy of exergames-acceptance and commitment therapy program for the treatment of major depressive disorder: comparison with acceptance and commitment therapy alone and treatment-as-usual in a multicentre randomised controlled trial.
BACKGROUND
The prevalence of major depressive disorder (MDD) is on the rise globally, and the use of antidepressant medications for its treatment does not usually result in full remission. However, the combination of physical exercise and psychotherapy for the treatment of MDD increase the rate of full remission among patients. This three-armed, parallel-group, double-blinded randomised controlled trial (RCT) aims to assess and compare the effects between the combination of exergame and acceptance and commitment therapy (e-ACT) programme, ACT only and treatment-as-usual (TAU) control groups on the severity of depression and anxiety symptoms, the degree of experiential avoidance and quality of life (QoL) and the serum levels of depression biomarkers (such as brain-derived neurotrophic factor, C-reactive protein and vascular endothelial growth factor) among patients with MDD across three time points.
METHODS AND ANALYSIS
This RCT will recruit 126 patients with MDD who will be randomised using stratified permuted block randomisation into three groups, which are the combined e-ACT programme, ACT-only and TAU control groups in a 1:1:1 allocation ratio. The participants in the e-ACT and ACT-only intervention groups will undergo once a week intervention sessions for 8 weeks. Assessments will be carried out through three time points, such as the pre-intervention assessment (t), assessment immediately after completion of the intervention at 8 weeks (t) and assessment at 24 weeks after completion of the intervention (t). During each assessment, the primary outcome to be assessed includes the severity of depression symptoms, while the secondary outcomes to be assessed are the severity of anxiety symptoms, experiential avoidance, QoL and depression biomarkers.
ETHICS AND DISSEMINATION
Approval of this study was obtained from the Human Research Ethics Committee of Universiti Sains Malaysia (USM/JEPeM/PP/23050420). The findings of the study will be published in academic peer-reviewed journals.
TRIAL REGISTRATION NUMBER
NCT05812001 (ClinicalTrials.gov). Registered on 12 April 2023.
Topics: Humans; Depressive Disorder, Major; Quality of Life; Acceptance and Commitment Therapy; Adult; Double-Blind Method; Male; Female; Video Games; Randomized Controlled Trials as Topic; Middle Aged; Treatment Outcome; Multicenter Studies as Topic; Exercise Therapy; Brain-Derived Neurotrophic Factor; Biomarkers
PubMed: 38926142
DOI: 10.1136/bmjopen-2023-080315 -
BMJ Open Jun 2024Chronic stress can cause an imbalance within the autonomic nervous system, thereby affecting cardiovascular and mental health. Physical activity (PA) may have a positive... (Observational Study)
Observational Study
INTRODUCTION
Chronic stress can cause an imbalance within the autonomic nervous system, thereby affecting cardiovascular and mental health. Physical activity (PA) may have a positive effect on the autonomic nervous system and stress-related disorders, such as depression and burnout. Heart rate variability (HRV) is a non-invasive marker of the autonomic nervous system. However, limited and inconsistent data exist on the exact relationship between HRV, PA and depression and burnout symptoms. The HARMODI study aims to explore whether HRV is a feasible marker of depression and burnout symptoms and aims to evaluate the role of PA in the treatment of stress-related disorders.
METHODS AND ANALYSES
This is an observational study with a cross-sectional up to 8 week follow-up study design. A total of 153 patients, undergoing psychiatric inpatient treatment with burnout syndrome (Z73) and depressive episode (F32 or F33) or adjustment disorder (F43.2), will be recruited. Data on depression and burnout symptoms, HRV recordings (24-hour, supine, standing and exercise stress test), cognitive function, cardiorespiratory fitness, cardiovascular health, balance and strength will be collected at baseline (T1) and after up to 8 weeks (T2). Continuous data on PA and Ecological Momentary Assessments of exhaustion, mood and tension will be monitored daily throughout inpatient treatment. Multiple regression models, adjusted for potential confounders, will assess the association between HRV as the primary outcome, PA and depression and burnout severity score.
ETHICS AND DISSEMINATION
The protocol has been approved by Swiss Ethics Committee, Cantonal Ethics Committee Zürich. Results of HARMODI will be disseminated through peer-reviewed journals and conference presentations.
TRIAL REGISTRATION NUMBER
NCT05874856.
Topics: Humans; Heart Rate; Cross-Sectional Studies; Exercise; Depression; Follow-Up Studies; Male; Adult; Burnout, Psychological; Female; Inpatients; Autonomic Nervous System; Middle Aged
PubMed: 38925684
DOI: 10.1136/bmjopen-2023-081299 -
Neuropsychopharmacology Reports Jun 2024The incidence of major depressive disorder (MDD) after heart transplantation is high; however, there are no reports on treatment options when antidepressant therapy...
The incidence of major depressive disorder (MDD) after heart transplantation is high; however, there are no reports on treatment options when antidepressant therapy fails to improve the condition. We herein report on the case of a woman with MDD after heart transplantation who partially improved with antidepressant treatment but continued to have a loss of appetite. Augmentation treatment with aripiprazole improved her appetite, and her MDD went into remission. When antidepressant treatment is not sufficiently effective for MDD after heart transplantation, augmentation treatment with antipsychotics, such as aripiprazole, should be considered.
PubMed: 38923862
DOI: 10.1002/npr2.12463