Parvalbumin interneuron alterations in stress-related mood disorders: A systematic review.
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ABSTRACT:
SUBMITTER: Perlman G
PROVIDER: S-EPMC8446799 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Working memory requires the activity of parvalbumin (PV) interneurons in the dorsolateral prefrontal cortex (DLPFC). Impaired working memory and lower PV expression in the DLPFC are reported in schizophrenia and to a lesser degree in mood disorders. We previously proposed that activity-dependent PV expression is lower in schizophrenia due to a shift in the splicing of erb-b2 receptor tyrosine kinase 4 (ErbB4) transcripts from major to inactive minor variants that reduces excitatory drive to PV interneurons. Here, we tested the hypothesis that the degree of major-to-minor shift in ErbB4 splicing predicts the level of PV expression across schizophrenia and mood disorders. Levels of ErbB4 splice variants and PV mRNA were quantified by PCR in the DLPFC from 40 matched tetrads (N = 160 subjects) of schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), and unaffected comparison subjects. Relative to unaffected comparison subjects, the magnitude of increases in minor variant levels and decreases in major variant levels was greatest in schizophrenia, intermediate in BD, and least in MDD. The same rank order was present for the magnitude of increases in the composite splicing score, which reflects the degree of major-to-minor shift across all ErbB4 splice loci, and for the magnitude of deficient PV expression. Finally, the composite splicing score negatively predicted PV expression across all subject groups. Together, these findings demonstrate a shared relationship between ErbB4 splicing and PV expression and suggest that scaling of the major-to-minor shift in ErbB4 splicing may influence the severity of deficient PV interneuron activity across diagnoses.
| S-EPMC6180093 | biostudies-literature
Project description:The neurobiological bases of mood instability are poorly understood. Neuronal network alterations and neurometabolic abnormalities have been implicated in the pathophysiology of mood and anxiety conditions associated with mood instability and hence are candidate mechanisms underlying its neurobiology. Fast-spiking parvalbumin GABAergic interneurons modulate the activity of principal excitatory neurons through their inhibitory action determining precise neuronal excitation balance. These interneurons are directly involved in generating neuronal networks activities responsible for sustaining higher cerebral functions and are especially vulnerable to metabolic stress associated with deficiency of energy substrates or mitochondrial dysfunction. Parvalbumin interneurons are therefore candidate key players involved in mechanisms underlying the pathogenesis of brain disorders associated with both neuronal networks' dysfunction and brain metabolism dysregulation. To provide empirical support to this hypothesis, we hereby report meta-analytical evidence of parvalbumin interneurons loss or dysfunction in the brain of patients with Bipolar Affective Disorder (BPAD), a condition primarily characterized by mood instability for which the pathophysiological role of mitochondrial dysfunction has recently emerged as critically important. We then present a comprehensive review of evidence from the literature illustrating the bidirectional relationship between deficiency in mitochondrial-dependent energy production and parvalbumin interneuron abnormalities. We propose a mechanistic explanation of how alterations in neuronal excitability, resulting from parvalbumin interneurons loss or dysfunction, might manifest clinically as mood instability, a poorly understood clinical phenotype typical of the most severe forms of affective disorders. The evidence we report provides insights on the broader therapeutic potential of pharmacologically targeting parvalbumin interneurons in psychiatric and neurological conditions characterized by both neurometabolic and neuroexcitability abnormalities.
| S-EPMC8488267 | biostudies-literature
Project description:BACKGROUND:Magnesium (Mg2+) has received considerable attention with regards to its potential role in the pathophysiology of the mood disorders, but the available evidence seems inconclusive.AimsTo review and quantitatively summarise the human literature on Mg2+ intake and Mg2+ blood levels in the mood disorders and the effects of Mg2+ supplements on mood. METHOD:Systematic review and meta-analyses. RESULTS:Adherence to a Mg2+-rich diet was negatively associated with depression in cross-sectional (odds ratio = 0.66) but not in prospective studies. Mg2+ levels in bodily fluids were on average higher in patients with a mood disorder (Hedge's g = 0.19), but only in patients treated with antidepressants and/or mood stabilisers. There was no evident association between Mg2+ levels and symptom severity. Mg2+ supplementation was associated with a decline in depressive symptoms in uncontrolled (g = -1.60) but not in placebo-controlled trials (g = -0.21). CONCLUSION:Our results provide little evidence for the involvement of Mg2+ in the mood disorders.Declaration of interestNone.
| S-EPMC6034436 | biostudies-literature
Project description:(1) Background: Obesity and mood disorders are considered as the most prevalent morbidities in many countries. We suppose that epigenetic mechanisms may induce higher rates of obesity in subjects who suffer from mood disorders. In this systematic review, we focused on the potential roles of DNA methylation on mood disorders and obesity development. (2) Methods: This systematic review was conducted in accordance with the PRISMA statement and registered in Prospero. A systematic search was conducted in MEDLINE, Scopus, Web of Science, Cochrane Central database, EMBASE, and CINHAL. We also conducted a Grey literature search, such as Google Scholar. (3) Results: After deduplication, we identified 198 potentially related citations. Finally, ten unique studies met our inclusion criteria. We have found three overlap genes that show significant DNA methylation changes, both in obesity and depression. Pathway analysis interaction for TAPBP, BDNF, and SORBS2 confirmed the relation of these genes in both obesity and mood disorders. (4) Conclusions: While mechanisms linking both obesity and mood disorders to epigenetic response are still unknown, we have already known chronic inflammation induces a novel epigenetic program. As the results of gene enrichment, pathways analysis showed that TAPBP, BDNF, and SORBS2 linked together by inflammatory pathways. Hypermethylation in these genes might play a crucial rule in the co-occurrence of obesity and mood disorders.
| S-EPMC7555814 | biostudies-literature
Project description:ObjectiveTwo primary compounds of the cannabis plant (Cannabis sativa), delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), differentially and dose-dependently affect mood and anxiety. In this systematic review, the authors summarize the design and results of controlled trials assessing the effects of THC and CBD on affective disorders, anxiety disorders, and posttraumatic stress disorder (PTSD).MethodsA keyword search of eight online literature databases identified eight randomized controlled trials of defined CBD or THC doses for the target populations.ResultsA 1-month trial of daily THC (up to 3 mg per day) for DSM-II anxiety disorder reduced anxiety symptoms, but symptoms were very low throughout the study. Another trial of sequential, single-day, low-dose THC in social anxiety disorder found no symptom changes. Two studies reported that single-dose CBD pretreatment reduced anxiety in laboratory paradigms among individuals with social anxiety disorder. A study of daily CBD for 4 weeks among adolescents with social anxiety disorder indicated modest symptom improvements. One crossover trial involving 10 patients with PTSD showed that THC added to standard pharmacotherapy reduced self-reported nightmares. Two small studies of THC for hospitalized patients with unipolar or bipolar depression found no improvement of depression; instead, anxiety and psychotic symptoms emerged in >50% of patients.ConclusionsWith only eight very small studies, insufficient evidence was found for efficacy of CBD and THC to manage affective disorders, anxiety disorders, or PTSD. Therefore, medical cannabis should not be recommended for treating patients with these disorders. Further research should investigate the safety and efficacy of managing psychiatric disorders with cannabinoids.
| S-EPMC8857699 | biostudies-literature
Project description:BackgroundTelemedicine has played a vital role in providing psychiatric treatment to patients during the rapid transition of services during the COVID-19 pandemic. Furthermore, the use of telemedicine is expected to expand within the psychiatric field. The efficacy of telemedicine is well described in scientific literature. However, there is a need for a comprehensive quantitative review that analyzes and considers the different clinical outcomes and psychiatric diagnoses.ObjectiveThis paper aimed to assess whether individual psychiatric outpatient treatment for posttraumatic stress disorder, mood disorders, and anxiety disorders in adults using telemedicine is equivalent to in-person treatment.MethodsA systematic search of randomized controlled trials was conducted using recognized databases for this review. Overall, 4 outcomes were assessed: treatment efficacy, levels of patient satisfaction, working alliance, and attrition rate. The inverse-variance method was used to summarize the effect size for each outcome.ResultsA total of 7414 records were identified, and 20 trials were included in the systematic review and meta-analysis. The trials included posttraumatic stress disorder (9 trials), depressive disorder (6 trials), a mix of different disorders (4 trials), and general anxiety disorder (1 trial). Overall, the analyses yielded evidence that telemedicine is comparable with in-person treatment regarding treatment efficacy (standardized mean difference -0.01, 95% CI -0.12 to 0.09; P=.84; I2=19%, 17 trials, n=1814), patient satisfaction mean difference (-0.66, 95% CI -1.60 to 0.28; P=.17; I2=44%, 6 trials, n=591), and attrition rates (risk ratio 1.07, 95% CI 0.94-1.21; P=.32; I2=0%, 20 trials, n=2804). The results also indicated that the working alliance between telemedicine and in-person modalities was comparable, but the heterogeneity was substantial to considerable (mean difference 0.95, 95% CI -0.47 to 2.38; P=.19; I2=75%, 6 trials, n=539).ConclusionsThis meta-analysis provided new knowledge on individual telemedicine interventions that were considered equivalent to in-person treatment regarding efficacy, patient satisfaction, working alliance, and attrition rates across diagnoses. The certainty of the evidence regarding efficacy was rated as moderate. Furthermore, high-quality randomized controlled trials are needed to strengthen the evidence base for treatment provided via telemedicine in psychiatry, particularly for personality disorders and a range of anxiety disorders where there is a lack of studies. Individual patient data meta-analysis is suggested for future studies to personalize telemedicine.Trial registrationPROSPERO International Prospective Register of Systematic Reviews CRD42021256357; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=256357.
| S-EPMC10357375 | biostudies-literature
Project description:Gluten related disorders (GRD) represent a wide spectrum of clinical manifestations that are triggered by the ingestion of gluten. Coeliac disease (CD) or gluten sensitive enteropathy is the most widely recognised, but extra-intestinal manifestations have also been increasingly identified and reported. Such manifestations may exist in the absence of enteropathy. Gluten sensitivity (GS) is another term that has been used to include all GRD, including those where there is serological positivity for GS related antibodies in the absence of an enteropathy. Gluten ataxia (GA) is the commonest extraintestinal neurological manifestation and it has been the subject of many publications. Other movement disorders (MDs) have also been reported in the context of GS. The aim of this review was to assess the current available medical literature concerning MDs and GS with and without enteropathy. A systematic search was performed while using PubMed database. A total of 48 articles met the inclusion criteria and were included in the present review. This review highlights that the phenomenology of gluten related MDs is broader than GA and demonstrates that gluten-free diet (GFD) is beneficial in a great percentage of such cases.
| S-EPMC6115931 | biostudies-other
Project description:Background: The clinical and etiological heterogeneity of mood disorders impede identification of effective treatments for the individual patient. This highlights a need for early neuronal and behavioral biomarkers for treatment efficacy, which can provide a basis for more personalized treatments. The present systematic review aimed to identify the most consistent neuronal and behavioral predictors of treatment efficacy on mood symptoms and cognitive impairment in mood disorders. Methods: We identified and included 60 original peer-reviewed studies investigating neuroimaging and behavioral predictors of treatment efficacy within the domains of emotional and non-emotional cognition, structural neuroimaging, and resting state functional connectivity in patients with unipolar or bipolar disorder. Results: Lower baseline responsivity in limbic regions coupled with heightened medial and dorsal prefrontal responses to emotional stimuli were the most consistent predictors of response to pharmacotherapy for depression. In contrast, heightened limbic and ventral prefrontal reactivity to emotional stimuli seemed to predict efficacy of psychological interventions. Early modulation of fronto-limbic activity and reduction in negative bias were also associated with treatment response. Better performance on non-emotional tests at baseline was relatively consistently associated with efficacy on mood symptoms, whereas the association between neural activity during non-emotional tests and treatment response was less clear. Other baseline factors associated with treatment response were greater white matter integrity, resting state functional connectivity, more prefrontal gray matter volume as well as an early increase following short administered treatment. Finally, emerging evidence indicates that baseline cognitive deficits are associated with greater chances of achieving treatment efficacy on cognition. Conclusions: Patients' profile of emotional and non-emotional cognition and neural activity-and the early treatment-associated changes in neural and cognitive function-may be useful for guiding treatments for depression. While cognitive deficits at baseline seem to improve chances of treatment efficacy on cognition, more studies of this association are urgently needed.
| S-EPMC6071514 | biostudies-literature
Project description:Stress disorders impair sleep and quality of life; however, their pathomechanisms are unknown. Prolactin-releasing peptide (PrRP) is a stress mediator; we therefore hypothesized that PrRP may be involved in the development of stress disorders. PrRP is produced by the medullary A1/A2 noradrenaline (NA) cells, which transmit stress signals to forebrain centers, and by non-NA cells in the hypothalamic dorsomedial nucleus. We found in male rats that both PrRP and PrRP-NA cells innervate melanin-concentrating hormone (MCH) producing neurons in the dorsolateral hypothalamus (DLH). These cells serve as a key hub for regulating sleep and affective states. Ex vivo, PrRP hyperpolarized MCH neurons and further increased the hyperpolarization caused by NA. Following sleep deprivation, intracerebroventricular PrRP injection reduced the number of REM sleep-active MCH cells. PrRP expression in the dorsomedial nucleus was upregulated by sleep deprivation, while downregulated by REM sleep rebound. Both in learned helplessness paradigm and after peripheral inflammation, impaired coping with sustained stress was associated with (1) overactivation of PrRP cells, (2) PrRP protein and receptor depletion in the DLH, and (3) dysregulation of MCH expression. Exposure to stress in the PrRP-insensitive period led to increased passive coping with stress. Normal PrRP signaling, therefore, seems to protect animals against stress-related disorders. PrRP signaling in the DLH is an important component of the PrRP's action, which may be mediated by MCH neurons. Moreover, PrRP receptors were downregulated in the DLH of human suicidal victims. As stress-related mental disorders are the leading cause of suicide, our findings may have particular translational relevance.SIGNIFICANCE STATEMENT Treatment resistance to monoaminergic antidepressants is a major problem. Neuropeptides that modulate the central monoaminergic signaling are promising targets for developing alternative therapeutic strategies. We found that stress-responsive prolactin-releasing peptide (PrRP) cells innervated melanin-concentrating hormone (MCH) neurons that are crucial in the regulation of sleep and mood. PrRP inhibited MCH cell activity and enhanced the inhibitory effect evoked by noradrenaline, a classic monoamine, on MCH neurons. We observed that impaired PrRP signaling led to failure in coping with chronic/repeated stress and was associated with altered MCH expression. We found alterations of the PrRP system also in suicidal human subjects. PrRP dysfunction may underlie stress disorders, and fine-tuning MCH activity by PrRP may be an important part of the mechanism.
| S-EPMC9899089 | biostudies-literature
Project description:OBJECTIVE:The objective was to conduct an update of a previously published review and meta-analysis on the association between work-related psychosocial risk factors and stress-related mental disorders (SRD). DESIGN:Systematic review and meta-analysis. DATA SOURCES:Medline, Embase and PsycINFO were searched for articles published between 2008 and 12 August 2019 and references of a systematic review performed for the period before 2008 were included. Primary prospective studies were included when outcome data were described in terms of SRD assessment or a dichotomous outcome, based on a validated questionnaire, and at least two levels of work-related exposure were reported (exposed vs less or non-exposed). We used GRADE to assess the evidence for the associations between risk factors and the onset of SRD. RESULTS:Seventeen studies met the inclusion criteria. In total, a population of 73 874 workers from Belgium, Denmark, England, Finland, Japan, the Netherlands and Sweden were included in the meta-analysis of 14 prospective cohort studies. This meta-analysis revealed moderate evidence for associations between SRD and effort reward imbalance (OR=1.9, 95% CI 1.70 to 2.15), high job demands (OR=1.6, 95% CI 1.41 to 1.72), organisational justice (ORs=1.6 to 1.7, CIs 1.44 to 1.86), social support (ORs=1.3 to 1.4, CIs 1.16 to 1.69), high emotional demands (OR=1.6, 95% CI 1.35 to 1.84) and decision authority (OR=1.3, CI 1.20 to 1.49). No significant or inconsistent associations were found for job insecurity, decision latitude, skill discretion and bullying. CONCLUSION:Moderate evidence was found that work-related psychosocial risk factors are associated with a higher risk of SRD. Effort-reward imbalance, low organisational justice and high job demands exhibited the largest increased risk of SRD, varying from 60% to 90%.
| S-EPMC7337889 | biostudies-literature