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Journal of Affective Disorders Jun 2024Major depressive disorder (MDD) is characterized by increased T helper (Th)1 polarization, T cell activation (e.g., CD71+ and CD40L+), and cannabinoid receptor type 2...
T cell activation and lowered T regulatory cell numbers are key processes in severe major depressive disorder: Effects of recurrence of illness and adverse childhood experiences.
BACKGROUND
Major depressive disorder (MDD) is characterized by increased T helper (Th)1 polarization, T cell activation (e.g., CD71+ and CD40L+), and cannabinoid receptor type 2 bearing CD20+ B cells; and lower T regulatory (Treg) numbers.
AIMS
To delineate the effects of adverse childhood experiences (ACEs) and recurrence of illness (ROI) on activated T and CB2-bearing B populations, and Tregs, including FoxP3 + CD152+, FoxP3 + GARP+, and FoxP3 + CB1+ cells.
METHODS
We measured ROI, ACEs, the number of activated T cells, Tregs, and CD20 + CB2+ B cells, in 30 MDD patients and 20 healthy controls.
RESULTS
A larger part of the variance in the depression phenome (40.8 %) was explained by increased CD20 + CB2+ and activated T cells, and lowered Tregs. ROI and lifetime suicidal behaviors were significantly and positively associated with CD20 + CB2+, CD3 + CD71+, CD3 + CD40L+, CD4 + CD71+, CD4 + CD40L+, and CD4HLADR+ numbers. ROI was significantly correlated with CD8 + CD40L+ numbers. The sum of ACEs was significantly associated with CD20 + CB2+, CD3 + CD40L+, CD4 + 40 L+ numbers, T cell activation (positively) and Treg (inversely) indices. One replicable latent vector could be extracted from activated T cells, lifetime and current suicidal behaviors, number of depressive episodes, and severity of depression, and 48.8 % of its variance was explained by ACEs.
CONCLUSIONS
ACE-induced activation of T effector and cytotoxic cells and B cells with autoimmune potential, coupled with lowered Treg numbers are a key component of depression. The findings indicate that increasing ROI, the phenome of depression and suicidal behaviors, are caused by autoimmune processes, which are the consequence of ACEs and increasing sensitization of immune responses.
PubMed: 38945402
DOI: 10.1016/j.jad.2024.06.097 -
Physiology & Behavior Jun 2024The roles of metabolic signals, including Glucagon-like peptide 1 (GLP-1), have been implicated in multiple domains outside metabolic regulation. There is a growing... (Review)
Review
INTRODUCTION
The roles of metabolic signals, including Glucagon-like peptide 1 (GLP-1), have been implicated in multiple domains outside metabolic regulation. There is a growing interest in repurposing Glucagon-like peptide 1 receptor agonists (GLP-1RAs) as therapeutics for motivation and reward-related behavioural disturbances. Herein, we aim to systematically review the extant evidence on the potential effects of GLP-1RAs on the reward system.
METHODS
The study followed PRISMA guidelines using databases such as OVID, PubMed, Scopus, and Google Scholar. The search focused on "Reward Behavior" and "Glucagon Like Peptide 1 Receptor Agonists" and was restricted to human studies. Quality assessment achieved by the NIH's Quality Assessment of Controlled Intervention Studies RESULTS: GLP-1RAs consistently reduced energy intake and influenced reward-related behaviour. These agents have been associated with decreased neurocortical activation in response to higher rewards and food cues, particularly high-calorie foods, and lowered caloric intake and hunger levels.
DISCUSSION
GLP-1RAs show promise in addressing reward dysfunction linked to food stimuli, obesity, and T2DM. They normalize insulin resistance, and might also modulate dopaminergic signalling and reduce anhedonia. Their effects on glycemic variability and cravings suggest potential applications in addiction disorders.
PubMed: 38945189
DOI: 10.1016/j.physbeh.2024.114622 -
Maternal Postpartum Depression Screening and Early Intervention in the Neonatal Intensive Care Unit.Advances in Pediatrics Aug 2024Families with infants admitted to the neonatal intensive care unit (NICU) are at a markedly increased risk of developing postpartum depression (PPD) because of the... (Review)
Review
Families with infants admitted to the neonatal intensive care unit (NICU) are at a markedly increased risk of developing postpartum depression (PPD) because of the stressors they experience by having an infant in this intensive setting. Routine screening for PPD is not regularly performed for these families because many NICUs do not offer it and well-child visits are missed while the infant is hospitalized. Because the identification and treatment of PPD is often missed in these families, screening needs to be administered in the NICU to ensure improved outcomes.
Topics: Humans; Depression, Postpartum; Female; Intensive Care Units, Neonatal; Infant, Newborn; Mass Screening; Risk Factors
PubMed: 38944489
DOI: 10.1016/j.yapd.2024.01.004 -
Journal of Affective Disorders Jun 2024Carbonyl stress, a metabolic state characterized by elevated production of reactive carbonyl compounds (RCCs), is closely related to oxidative stress and has been...
BACKGROUND
Carbonyl stress, a metabolic state characterized by elevated production of reactive carbonyl compounds (RCCs), is closely related to oxidative stress and has been implicated in various diseases. This study aims to investigate carbonyl stress parameters in drug-free bipolar disorder (BD) patients compared to healthy controls, explore their relationship with clinical features, and assess the effect of treatment on these parameters.
METHODS
Patients with a primary diagnosis of a manic episode of BD and healthy controls were recruited. Exclusion criteria included intellectual disability, presence of neurological diseases, chronic medical conditions such as diabetes mellitus and metabolic syndrome, and clinical signs of inflammation. Levels of serum carbonyl stress parameters were determined using high-performance liquid chromatography.
RESULTS
Levels of glyoxal (GO) and methylglyoxal (MGO) did not differ between pre- and post-treatment patients, but malondialdehyde (MDA) levels decreased significantly post-treatment. Pre-treatment MGO and MDA levels were higher in patients compared to controls, and these differences persisted post-treatment. After adjusting for BMI and waist circumference, only MDA levels remained significantly higher in patients compared to controls.
LIMITATIONS
The study's limitations include the exclusion of female patients, which precluded any assessment of potential gender differences, and the lack of analysis of the effect of specific mood stabilizers or antipsychotic drugs.
CONCLUSIONS
This study is the first to focus on carbonyl stress markers in BD, specifically GO, MGO, and MDA. MDA levels remained significantly higher in patients, suggesting a potential role in BD pathophysiology. MGO levels were influenced by metabolic parameters, indicating a potential link to neurotoxicity in BD. Further research with larger cohorts is needed to better understand the role of RCCs in BD and their potential as therapeutic targets.
PubMed: 38944288
DOI: 10.1016/j.jad.2024.06.112 -
Biological Psychiatry Jun 2024Insomnia disorder is the most common sleep disorder. A better understanding of insomnia-related deviations in the brain could inspire better treatment. Insufficiently...
OBJECTIVE
Insomnia disorder is the most common sleep disorder. A better understanding of insomnia-related deviations in the brain could inspire better treatment. Insufficiently recognized heterogeneity within the insomnia population could obscure detection of involved brain circuits. The present study investigated whether structural brain connectivity deviations differ between recently discovered and validated insomnia subtypes.
METHODS
Structural and diffusion weighted 3-Tesla MRI data of four independent studies were harmonized. The sample consisted of 73 controls without sleep complaints and 204 participants with insomnia grouped into five subtypes based on their fingerprint of mood and personality traits assessed with the Insomnia Type Questionnaire. Linear regression correcting for age and sex evaluated group differences in structural connectivity strength, indicated by fractional anisotropy, streamline volume density and mean diffusivity, and evaluated within three different atlases.
RESULTS
Insomnia subtypes showed differentiating profiles of deviating structural connectivity which concentrated in different functional networks. Permutation testing against randomly drawn heterogeneous subsamples indicated significant specificity of deviation profiles in four of the five subtypes: highly distressed, moderately distressed reward sensitive, slightly distressed low reactive and slightly distressed high reactive. Connectivity deviation profile significance ranged from p= 0.001 to p=0.049 for different resolutions of brain parcellation and connectivity weight.
CONCLUSIONS
Our results provide a first indication that different insomnia subtypes exhibit distinct profiles of deviations in structural brain connectivity. Subtyping of insomnia could be essential for a better understanding of brain mechanisms that contribute to insomnia vulnerability.
PubMed: 38944140
DOI: 10.1016/j.biopsych.2024.06.014 -
Peptides Jun 2024This paper is the forty-sixth consecutive installment of the annual anthological review of research concerning the endogenous opioid system, summarizing articles... (Review)
Review
This paper is the forty-sixth consecutive installment of the annual anthological review of research concerning the endogenous opioid system, summarizing articles published during 2023 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides and receptors as well as effects of opioid/opiate agonists and antagonists. The review is subdivided into the following specific topics: molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors (1), the roles of these opioid peptides and receptors in pain and analgesia in animals (2) and humans (3), opioid-sensitive and opioid-insensitive effects of nonopioid analgesics (4), opioid peptide and receptor involvement in tolerance and dependence (5), stress and social status (6), learning and memory (7), eating and drinking (8), drug and alcohol abuse (9), sexual activity and hormones, pregnancy, development and endocrinology (10), mental illness and mood (11), seizures and neurologic disorders (12), electrical-related activity and neurophysiology (13), general activity and locomotion (14), gastrointestinal, renal and hepatic functions (15), cardiovascular responses (16), respiration and thermoregulation (17), and immunological responses (18).
PubMed: 38943841
DOI: 10.1016/j.peptides.2024.171268 -
Brain Research Jun 2024Oxidative stress plays a pivotal role in various neurological disorders, encompassing both neurodegenerative diseases such as Alzheimer's and Parkinson's, and mood...
Oxidative stress plays a pivotal role in various neurological disorders, encompassing both neurodegenerative diseases such as Alzheimer's and Parkinson's, and mood disorders like depression. The balance between the generation of reactive oxygen species (ROS) and the cell's antioxidant defenses, when disrupted, can lead to neuronal damage and neurologic dysfunction. In this study, we focused on the pathogenic role of oxidative stress in various neurologic disease models in vitro and investigated the neuroprotective capabilities of some novel bicyclic γ-butyrolactone compounds, with particular emphasis on the compound designated as 'bd'. Our investigation leveraged the HT22 and SH-SY5Y cells to model oxidative stress induced by HO or corticosterone (CORT), common triggers of neuronal damage in neurodegenerative and mood disorders. We discovered that compound bd robustly reduced ROS production and suppressed neuronal apoptosis, suggesting its potential in treating a wider array of neurological conditions influenced by oxidative stress. In conclusion, our research underscores the importance of addressing oxidative stress in the context of diverse neurological disorders. The identification of compound bd as a neuroprotective agent with potential efficacy against ROS-induced apoptosis in neural cells opens new horizons for therapeutic development, offering hope for patients suffering from neurodegenerative diseases, depression, and other stress-related neurological conditions.
PubMed: 38942352
DOI: 10.1016/j.brainres.2024.149099 -
Journal of the Academy of... Jun 2024Adverse Childhood Experiences (ACE) are associated with the development of negative health behaviors and medical illness. ACE's association with poor health outcomes has...
INTRODUCTION
Adverse Childhood Experiences (ACE) are associated with the development of negative health behaviors and medical illness. ACE's association with poor health outcomes has been well documented in the general population; however, this relationship remains less clear in liver transplant (LT) recipients. The aims of this study therefore were to determine the prevalence of ACE and the influence of ACE on LT outcomes.
METHODS
A retrospective electronic medical record review of all LT recipients over 11 years at an academic liver transplant center. Demographic, diagnostic, and disease characteristics were extracted and compared for a history of ACE. Associations between a history of ACE and extracted variables were statistically tested using Student's t-test and Chi-square tests or Fisher's Exact Test where appropriate. Graft and patient survival were tested using log-rank tests.
RESULTS
Of 1,172 LT recipients, 24.1% endorsed a history of ACE. Females (p = 0.017) and recipients with lower level of education (p < 0.001) had a higher frequency of ACE. Those with a history of ACE had a higher prevalence of HCV (p < 0.001) and higher pre-transplant BMI (P<0.001). Recipients with a history of ACE had higher prevalence of mood (p < 0.001), anxiety (p < 0.001), PTSD (p < 0.001), alcohol use (p < 0.001), and cannabis use (p < 0.001) disorders as well has higher PHQ-9 (p < 0.001) and GAD-7 (p < 0.001) scores pre and post-transplant. Those with ACE had higher incidence of recorded relapse to alcohol by 3 years post-transplant (p = 0.027). Mean lab values, graft survival, and patient survival were not significantly different between those with and without a history of ACE except for total bilirubin at 6 months (p = 0.021).
CONCLUSION
One quarter of LT recipients have experienced ACE. ACE was associated with a history of a psychiatric diagnoses, substance use disorders, elevated PHQ-9 and GAD-7 scores, and a higher prevalence of relapse to alcohol use after transplant. This population may benefit from increased/improved access to appropriate mental health and substance use services and support in the peri and post transplant period.
PubMed: 38942236
DOI: 10.1016/j.jaclp.2024.06.006 -
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 -
Clinical Psychology Review Jun 2024The purpose of the current review was to address four questions: 1) Are there differences in family functioning or family environment among patients with different... (Review)
Review
The purpose of the current review was to address four questions: 1) Are there differences in family functioning or family environment among patients with different eating disorder (ED) diagnoses? 2) Are there differences in the perception of family functioning or family environment among different family members? 3) Is family functioning or family environment related to ED symptomatology? 4) Does family functioning or family environment change as a result of ED treatment? and 4a) If so, does this impact ED treatment outcome? Although most studies found no differences among ED diagnostic groups, those that did generally found worse family functioning among those with binge/purge symptoms than among those with the restricting subtype of anorexia nervosa. Differences in perceptions of family functioning among family members were found, with patients generally reporting worse functioning than their parents. Worse family functioning was generally found to be related to worse ED symptoms. The variety of treatment approaches and different assessments of outcome made it somewhat unclear whether family functioning consistently improves with ED treatment. More research is needed on family functioning and EDs, particularly in understudied groups such as males, and those with ED diagnoses other than anorexia nervosa or bulimia nervosa.
PubMed: 38941693
DOI: 10.1016/j.cpr.2024.102462