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The European Journal of Neuroscience May 2022Regulation of emotions is generally associated exclusively with the brain. However, there is evidence that peripheral systems are also involved in mood, stress... (Review)
Review
Regulation of emotions is generally associated exclusively with the brain. However, there is evidence that peripheral systems are also involved in mood, stress vulnerability vs. resilience, and emotion-related memory encoding. Prevalence of stress and mood disorders such as major depression, bipolar disorder, and post-traumatic stress disorder is increasing in our modern societies. Unfortunately, 30%-50% of individuals respond poorly to currently available treatments highlighting the need to further investigate emotion-related biology to gain mechanistic insights that could lead to innovative therapies. Here, we provide an overview of inflammation-related mechanisms involved in mood regulation and stress responses discovered using animal models. If clinical studies are available, we discuss translational value of these findings including limitations. Neuroimmune mechanisms of depression and maladaptive stress responses have been receiving increasing attention, and thus, the first part is centered on inflammation and dysregulation of brain and circulating cytokines in stress and mood disorders. Next, recent studies supporting a role for inflammation-driven leakiness of the blood-brain and gut barriers in emotion regulation and mood are highlighted. Stress-induced exacerbated inflammation fragilizes these barriers which become hyperpermeable through loss of integrity and altered biology. At the gut level, this could be associated with dysbiosis, an imbalance in microbial communities, and alteration of the gut-brain axis which is central to production of mood-related neurotransmitter serotonin. Novel therapeutic approaches such as anti-inflammatory drugs, the fast-acting antidepressant ketamine, and probiotics could directly act on the mechanisms described here improving mood disorder-associated symptomatology. Discovery of biomarkers has been a challenging quest in psychiatry, and we end by listing promising targets worth further investigation.
Topics: Animals; Antidepressive Agents; Bipolar Disorder; Brain; Inflammation; Mood Disorders
PubMed: 33876886
DOI: 10.1111/ejn.15239 -
Biological Psychiatry Mar 2022Transcriptome studies have revealed age-, disease-, and region-associated microglial phenotypes reflecting changes in microglial function during development, aging,...
BACKGROUND
Transcriptome studies have revealed age-, disease-, and region-associated microglial phenotypes reflecting changes in microglial function during development, aging, central nervous system homeostasis, and pathology. The molecular mechanisms that contribute to these transcriptomic changes are largely unknown. The aim of this study was to characterize the DNA methylation landscape of human microglia and the factors that contribute to variations in the microglia methylome. We hypothesized that both age and brain region would have a large impact on DNA methylation in microglia.
METHODS
Microglia from postmortem brain tissue of four different brain regions of 22 donors, encompassing 1 patient with schizophrenia, 13 patients with mood disorder pathology, and 8 control subjects, were isolated and assayed using a genome-wide methylation array.
RESULTS
We found that human microglial cells have a methylation profile distinct from bulk brain tissue and neurons, and age explained a considerable part of the variation. Additionally, we showed that interindividual factors had a much larger effect on the methylation landscape of microglia than brain region, which was also seen at the transcriptome level. In our exploratory analysis, we found various differentially methylated regions that were related to disease status (mood disorder vs. control). This included differentially methylated regions that are linked to gene expression in microglia, as well as to myeloid cell function or neuropsychiatric disorders.
CONCLUSIONS
Although based on relatively small samples, these findings suggest that the methylation profile of microglia is responsive to interindividual variations and thereby plays an important role in the heterogeneity of microglia observed at the transcriptome level.
Topics: Brain; DNA Methylation; Epigenome; Humans; Microglia; Mood Disorders; Transcriptome
PubMed: 35027166
DOI: 10.1016/j.biopsych.2021.10.020 -
Science & Practice Perspectives Dec 2005Mood disorders, including depression and bipolar disorders, are the most common psychiatric comorbidities among patients with substance use disorders. Treating patients'... (Review)
Review
Mood disorders, including depression and bipolar disorders, are the most common psychiatric comorbidities among patients with substance use disorders. Treating patients' co-occurring mood disorders may reduce their substance craving and taking and enhance their overall outcomes. A methodical, staged screening and assessment can ease the diagnostic challenge of distinguishing symptoms of affective disorders from manifestations of substance intoxication and withdrawal. Treatment should maximize the use of psychotherapeutic interventions and give first consideration to medications proven effective in the context of co-occurring substance abuse. Expanded communication and collaboration between substance abuse and mental health providers is crucial to improving outcomes for patients with these complex, difficult co-occurring disorders.
Topics: Cognitive Behavioral Therapy; Comorbidity; Diagnosis, Differential; Humans; Mood Disorders; Psychotropic Drugs; Self-Help Groups; Substance-Related Disorders
PubMed: 18552741
DOI: 10.1151/spp053113 -
Current Psychiatry Reports Oct 2021In contrast to premenstrual dysphoric disorder (PMDD), premenstrual exacerbations (PMEs) of ongoing mood disorders are understudied. The aim of this review is to... (Review)
Review
PURPOSE OF REVIEW
In contrast to premenstrual dysphoric disorder (PMDD), premenstrual exacerbations (PMEs) of ongoing mood disorders are understudied. The aim of this review is to describe diagnostic issues, epidemiology, underlying mechanisms, and treatment for PME in unipolar depression and bipolar disorder, and to discuss clinical and research implications.
RECENT FINDINGS
Community-based and clinical studies estimate that in women with mood disorders around 60% report PME, while some women with bipolar disorder also show symptom exacerbations around ovulation. In general, PME predicts a more severe illness course and an increased burden. While heightened sensitivity to fluctuations of sex hormone levels across the menstrual cycle appears to contribute to PME and PMDD, the overlap of their underlying biological mechanisms remains unclear. Beneficial treatments for PMDD show less or no efficacy in PME. Pharmacological treatments for PME in mood disorders predominantly seem to profit from adjustable augmentation of treatment dosages during the luteal phase for the underlying disorder. However, the evidence is sparse and mainly based on earlier small studies and case reports. Previous research is mainly limited by the lack of a clear differentiation between PME and PMDD comorbidity with mood disorders. More systematic research with uniformly defined and prospectively assessed subgroups of PME in larger epidemiological and clinical samples is needed to receive reliable prevalence estimates and information on the clinical impact of PME of mood disorders, and to uncover underlying mechanisms. In addition, larger randomized controlled trials are warranted to identify efficacious pharmacological and psychotherapeutic treatments for affected women.
Topics: Female; Humans; Luteal Phase; Menstrual Cycle; Mood Disorders; Premenstrual Dysphoric Disorder; Premenstrual Syndrome
PubMed: 34626258
DOI: 10.1007/s11920-021-01286-0 -
Neuroimmunomodulation 2021Mood disorders are associated with chronic low-grade systemic (sterile) inflammation, with increased plasma levels of pro-inflammatory mediators targeting all tissues... (Review)
Review
Mood disorders are associated with chronic low-grade systemic (sterile) inflammation, with increased plasma levels of pro-inflammatory mediators targeting all tissues including the brain. Importantly, pro-inflammatory cytokines (ex., tumor-necrosis factor alpha [TNF-α], interleukin [IL]-6) regulate mood behavior and cognition by influencing neurotransmitter levels, activating stress-responsive endocrine axes, among other effects. However, the mechanisms underlying this enhanced inflammation are not well understood. There is increasing evidence indicating that impaired immunoregulatory mechanisms may play a role in this context. Patients with mood disorders (major depression [MDD] and bipolar disorder [BD]) have reduced numbers of major regulatory cells of both innate (natural killer regulatory cells and myeloid-derived suppressor cells [MDSCs]) and adaptive immune responses (CD4+CD25+FoxP3+, B regulatory cells). Dysfunctional regulatory immune cells might contribute to systemic and neuroinflammation observed in mood disorders via different mechanisms, such as: (i) failure to develop adequate stress-related responses, (ii) indirectly through microglial activation, (iii) lack of trophic support and pro-cognitive functions of T cells in the brain, and (iv) dysbiosis. In conclusion, maladaptive immunoregulatory mechanisms seem to be involved with both onset and progression of mood disorders. A deeper understanding of these mechanisms may lead to the development of new therapeutic strategies.
Topics: Bipolar Disorder; Cytokines; Depressive Disorder, Major; Humans; Inflammation; Mood Disorders
PubMed: 33951643
DOI: 10.1159/000515594 -
Psychopharmacology Feb 2021Major depressive disorder is one of the leading global causes of disability, for which the classic serotonergic psychedelics have recently reemerged as a potential... (Meta-Analysis)
Meta-Analysis Review
RATIONALE
Major depressive disorder is one of the leading global causes of disability, for which the classic serotonergic psychedelics have recently reemerged as a potential therapeutic treatment option.
OBJECTIVE
We present the first meta-analytic review evaluating the clinical effects of classic serotonergic psychedelics vs placebo for mood state and symptoms of depression in both healthy and clinical populations (separately).
RESULTS
Our search revealed 12 eligible studies (n = 257; 124 healthy participants, and 133 patients with mood disorders), with data from randomized controlled trials involving psilocybin (n = 8), lysergic acid diethylamide ([LSD]; n = 3), and ayahuasca (n = 1). The meta-analyses of acute mood outcomes (3 h to 1 day after treatment) for healthy volunteers and patients revealed improvements with moderate significant effect sizes in favor of psychedelics, as well as for the longer-term (16 to 60 days after treatments) mood state of patients. For patients with mood disorder, significant effect sizes were detected on the acute, medium (2-7 days after treatment), and longer-term outcomes favoring psychedelics on the reduction of depressive symptoms.
CONCLUSION
Despite the concerns over unblinding and expectancy, the strength of the effect sizes, fast onset, and enduring therapeutic effects of these psychotherapeutic agents encourage further double-blind, placebo-controlled clinical trials assessing them for management of negative mood and depressive symptoms.
Topics: Affect; Banisteriopsis; Depression; Depressive Disorder, Major; Double-Blind Method; Hallucinogens; Healthy Volunteers; Humans; Lysergic Acid Diethylamide; Mood Disorders; Psilocybin; Randomized Controlled Trials as Topic; Serotonin Receptor Agonists; Treatment Outcome
PubMed: 33427944
DOI: 10.1007/s00213-020-05719-1 -
International Journal of Molecular... Feb 2021Mood disorders are chronic, recurrent diseases characterized by changes in mood and emotions. The most common are major depressive disorder (MDD) and bipolar disorder... (Review)
Review
Mood disorders are chronic, recurrent diseases characterized by changes in mood and emotions. The most common are major depressive disorder (MDD) and bipolar disorder (BD). Molecular biology studies have indicated an involvement of the immune system in the pathogenesis of mood disorders, and showed their correlation with altered levels of inflammatory markers and energy metabolism. Previous reports, including meta-analyses, also suggested the role of microglia activation in the M1 polarized macrophages, reflecting the pro-inflammatory phenotype. Lithium is an effective mood stabilizer used to treat both manic and depressive episodes in bipolar disorder, and as an augmentation of the antidepressant treatment of depression with a multidimensional mode of action. This review aims to summarize the molecular studies regarding inflammation, microglia activation and energy metabolism changes in mood disorders. We also aimed to outline the impact of lithium on these changes and discuss its immunomodulatory effect in mood disorders.
Topics: Animals; Biomarkers; Cytokines; Disease Management; Disease Susceptibility; Energy Metabolism; Humans; Immunomodulation; Inflammation; Inflammation Mediators; Lithium; Mood Disorders
PubMed: 33546417
DOI: 10.3390/ijms22041532 -
Dialogues in Clinical Neuroscience Jun 2015Recognition and management of mood symptoms in individuals using alcohol and/or other drugs represent a daily challenge for clinicians in both inpatient and outpatient... (Review)
Review
Recognition and management of mood symptoms in individuals using alcohol and/or other drugs represent a daily challenge for clinicians in both inpatient and outpatient treatment settings. Diagnosis of underlying mood disorders in the context of ongoing substance abuse requires careful collection of psychiatric history, and is often critical for optimal treatment planning and outcomes. Failure to recognize major depression or bipolar disorders in these patients can result in increased relapse rates, recurrence of mood episodes, and elevated risk of completed suicide. Over the past decade, epidemiologic research has clarified the prevalence of comorbid mood disorders in substance-dependent individuals, overturning previous assumptions that depression in these patients is simply an artifact of intoxication and/or withdrawal, therefore requiring no treatment. However, our understanding of the bidirectional relationships between mood and substance use disorders in terms of their course(s) of illness and prognoses remains limited. Like-wise, strikingly little treatment research exists to guide clinical decision making in co-occurring mood and substance use disorders, given their high prevalence and public health burden. Here we overview what is known and the salient gaps of knowledge where data might enhance diagnosis and treatment of these complicated patients.
Topics: Comorbidity; Disease Progression; Humans; Mood Disorders; Outcome Assessment, Health Care; Prevalence; Substance-Related Disorders
PubMed: 26246792
DOI: 10.31887/DCNS.2015.17.2/btolliver -
Zeitschrift Fur Kinder- Und... Jan 2018According to DSM-5, Disruptive Mood Dysregulation Disorder (DMDD) is characterized by chronic temper outbursts and irritable moods. So far, little is known about its...
OBJECTIVE
According to DSM-5, Disruptive Mood Dysregulation Disorder (DMDD) is characterized by chronic temper outbursts and irritable moods. So far, little is known about its prevalence rate, course and influence on individual well-being. We assessed the prevalence rates of DMDD symptoms during adulthood and primary school age - the latter retrospectively - and studied their relationship with psychiatric disorders and socioeconomic variables.
METHODS
A total of 2,413 subjects, aged 18-94 years, participated in this population-based, representative study based on self-reports.
RESULTS
12 (0.50 %) subjects reported elevated DMDD symptoms during adulthood, and 19 (0.79 %) reported elevated DMDD symptoms during primary school age. DMDD symptoms were associated with higher rates of depression and anxiety symptoms. Those reporting elevated DMDD symptoms during adulthood were more often single or divorced, and those reporting elevated DMDD symptoms during primary school age were more often childless and unemployed during adulthood compared to subjects without DMDD symptoms.
CONCLUSIONS
DMDD symptoms seem to show a chronic course and go hand in hand with elevated psychiatric symptoms and impaired socioeconomic and demographic status.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anger; Anxiety Disorders; Attention Deficit and Disruptive Behavior Disorders; Child; Chronic Disease; Comorbidity; Cross-Sectional Studies; Depressive Disorder; Female; Health Surveys; Humans; Irritable Mood; Male; Middle Aged; Mood Disorders; Retrospective Studies; Social Adjustment; Young Adult
PubMed: 29067863
DOI: 10.1024/1422-4917/a000552 -
Psychological Medicine Oct 2022Mood disorders, including depressive and bipolar disorders, represent a multidimensional and prevalent group of psychiatric illnesses characterized by disturbances in... (Review)
Review
Mood disorders, including depressive and bipolar disorders, represent a multidimensional and prevalent group of psychiatric illnesses characterized by disturbances in emotion, cognition and metabolism. Maladaptive eating behaviors in mood disorders are diverse and warrant characterization in order to increase the precision of diagnostic criteria, identify subtypes and improve treatment strategies. The current narrative review synthesizes evidence for Eating Behavioral Phenotypes (EBP) in mood disorders as well as advancements in pathophysiological conceptual frameworks relevant to each phenotype. Phenotypes include maladaptive eating behaviors related to appetite, emotion, reward, impulsivity, diet style and circadian rhythm disruption. Potential treatment strategies for each phenotype are also discussed, including psychotherapeutic, pharmacological and nutritional interventions. Maladaptive eating behaviors related to mood disorders are relevant from both clinical and research perspectives, yet have been somewhat overlooked thus far. A better understanding of this aspect of mood disorders holds promise to improve clinical care in this patient group and contribute to the subtyping of these currently subjectively diagnosed and treated disorders.
Topics: Humans; Mood Disorders; Bipolar Disorder; Emotions; Impulsive Behavior; Phenotype
PubMed: 36004528
DOI: 10.1017/S0033291722002446