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Neuroscience and Biobehavioral Reviews Jul 2019We aimed to perform a systematic review and meta-analysis of appetite regulating hormones in patients with first-episode psychosis (FEP). Meta-analyses were conducted... (Meta-Analysis)
Meta-Analysis
We aimed to perform a systematic review and meta-analysis of appetite regulating hormones in patients with first-episode psychosis (FEP). Meta-analyses were conducted using random-effects models with Hedges' g as the effect size estimate. We identified 31 eligible studies, investigating the levels of 7 appetite regulating hormones (adiponectin, insulin, leptin, ghrelin, orexin, resistin and visfatin) in 1792 FEP patients and 1364 controls. The insulin levels in FEP patients were higher than in controls (g = 0.34, 95%CI: 0.19 - 0.49, p < 0.001), even considering only antipsychotic-naïve patients (g = 0.39, 95%CI: 0.12 - 0.66, p = 0.005). The severity of negative symptoms was positively associated with the effect size estimates (β = 0.08, 95%CI: 0.01 - 0.16, p = 0.030). Moreover, we found lower levels of leptin in antipsychotic-naïve FEP patients (g = -0.62, 95%CI: -1.11 - 0.12, p = 0.015). Impaired appetite regulation, in terms of elevated insulin levels and decreased leptin levels, occurs in early psychosis, before antipsychotic treatment. Hyperinsulinemia might be related to negative symptoms.
Topics: Appetite Regulation; Humans; Insulin; Leptin; Obesity; Psychotic Disorders; Schizophrenia
PubMed: 31121198
DOI: 10.1016/j.neubiorev.2019.05.018 -
Journal of Affective Disorders May 2019Major depressive disorder (MDD) is a complex and heterogeneous disorder in which clinical symptoms can widely differ among patients. Neurovegetative symptoms, i.e....
BACKGROUND
Major depressive disorder (MDD) is a complex and heterogeneous disorder in which clinical symptoms can widely differ among patients. Neurovegetative symptoms, i.e. decreased or increased appetite, changes in body weight and sleep disturbances, described as 'melancholic' or 'atypical' features of a depressive episode, are the most variable symptoms among patients with MDD. We hypothesized biomarkers differences underlying this neurovegetative variability in major depression.
METHODS
We systematically reviewed, according to the PRISMA guidelines, the role of specific metabolic, hormonal and inflammatory biomarkers in drug-free MDD patients, that could have neurobiological effects on appetite, weight regulation and circadian rhythms, influencing eating behaviour and sleep patterns. All studies regarding the co-occurrence of disturbed sleep and appetite were examined.
RESULTS
Besides the well-known leptin and ghrelin, other biomarkers such as BDNF, VEGF, NPY, orexin, and the recent discovered nesfatin-1 seem to be involved in neurovegetative changes in depressive disorders playing a role in the regulation of affective states, stress reactions and sleep patterns. Interestingly, based on the existing evidence, ghrelin, orexin and nesfatin-1 could be linked both to sleep and appetite regulation in depressed patients.
LIMITATIONS
Heterogeneous studies with low sample size.
CONCLUSIONS
Despite the wide heterogeneity of results, studies on biomarkers of appetite and sleep in MDD are an interesting field of research to explain the neurobiological substrates of depressive symptoms that deserve further investigation.
Topics: Appetite; Biomarkers; Depressive Disorder, Major; Energy Metabolism; Hormones; Humans; Inflammation Mediators; Sleep
PubMed: 30870775
DOI: 10.1016/j.jad.2019.03.015 -
Current Opinion in Psychiatry Mar 2018Research interest in sleep as a risk factor for dementia has grown, warranting an update in advances over the last 18 months, particularly in the mild cognitive...
PURPOSE OF REVIEW
Research interest in sleep as a risk factor for dementia has grown, warranting an update in advances over the last 18 months, particularly in the mild cognitive impairment (MCI) stage in which interventions may be best targeted.
RECENT FINDINGS
The current systematic review includes empiric research articles published since 2016 that have investigated sleep (excluding obstructive sleep apnea) in MCI. Published articles include case-control studies, those examining clinical correlates of sleep problems, sleep microarchitecture, neuroimaging studies and novel cerebrospinal and blood-based markers.
SUMMARY
Evidence accumulated since 2016 continues to demonstrate that people with MCI manifest sleep disturbance on self-report measures. Neurophysiologically, sleep disturbance in MCI appears to be associated with diminished sleep spindles, key processes involved in overnight memory consolidation. Those with both MCI and sleep disturbance appear to have more pronounced functional connectivity alterations in temporoparietal brain regions and higher levels of the wake-promoting neurotransmitter orexin in cerebrospinal fluid than those with MCI alone. Novel findings also suggest that sleep may mediate homocysteine and oxidative stress mechanisms, warranting further exploration. Further studies focusing on novel interventions for sleep and circadian disturbance in MCI are warranted, particularly those targeting sleep spindles, orexin/hypocretin and the oxidative stress system.
Topics: Biomarkers; Brain; Circadian Clocks; Cognitive Dysfunction; Homocysteine; Humans; Orexins; Oxidative Stress; Risk Factors; Sleep; Sleep Wake Disorders
PubMed: 29256922
DOI: 10.1097/YCO.0000000000000397 -
Sleep Medicine Reviews Oct 2017Suvorexant is a dual orexin receptor agonist and is currently approved for the treatment of insomnia in the United States and Japan. We conducted a systematic review and... (Meta-Analysis)
Meta-Analysis Review
Suvorexant is a dual orexin receptor agonist and is currently approved for the treatment of insomnia in the United States and Japan. We conducted a systematic review and meta-analysis to assess the efficacy and safety of suvorexant for the treatment of primary insomnia. We searched PubMed, EMBASE, and the Cochrane central register of controlled trials, contacted a relevant pharmaceutical company, and accessed websites of the U.S. Food and Drug Administration (FDA) and Pharmaceuticals and Medical Devices Agency (PMDA) for published and unpublished data. A total of four randomized trials involving 3076 patients with primary insomnia were included in our analysis. Our analysis suggested that suvorexant was associated with significant improvements in subjective time to sleep onset, subjective total sleep time, and subjective quality of sleep at 1 mo and 3 mo. Somnolence, fatigue, and abnormal dreams were the most common adverse effects. We concluded that suvorexant was associated with improvement in some sleep parameters and some adverse effects. To determine the place of suvorexant in the treatment of insomnia, comparative effectiveness trials are needed.
Topics: Azepines; Humans; Japan; Randomized Controlled Trials as Topic; Sleep Aids, Pharmaceutical; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Triazoles; United States
PubMed: 28365447
DOI: 10.1016/j.smrv.2016.09.004 -
Italian Journal of Pediatrics Mar 2017Obesity and headache are two highly prevalent diseases both in adults and children and they are associated with a strong personal and social impact. Many studies suggest... (Review)
Review
Obesity and headache are two highly prevalent diseases both in adults and children and they are associated with a strong personal and social impact. Many studies suggest that obesity is comorbid with headache in general, and migraine in particular and obesity seems to be a risk factor for migraine progression and for migraine frequency both in adults and in children. Research shows that there are multiple areas of overlap between migraine pathophysiology and the central and peripheral pathways regulating feeding: inflammatory mediators such as the calcitonin gene-related protein (CGRP), neurotransmitters such as serotonin, peptides such as orexin and adipocytokines such as adiponectin (ADP) and leptin could explain the common pathogenesis. In this paper we discussed the association between obesity and migraine through the analysis of the most recent studies in children and we reviewed data from literature in order to assess the association between obesity and headache and to clarify the possible common pathogenic mechanisms.
Topics: Child; Comorbidity; Global Health; Humans; Migraine Disorders; Pediatric Obesity; Risk Assessment; Risk Factors
PubMed: 28270183
DOI: 10.1186/s13052-017-0344-1 -
European Neuropsychopharmacology : the... Nov 2015Modafinil is an FDA-approved eugeroic that directly increases cortical catecholamine levels, indirectly upregulates cerebral serotonin, glutamate, orexin, and histamine... (Review)
Review
Modafinil is an FDA-approved eugeroic that directly increases cortical catecholamine levels, indirectly upregulates cerebral serotonin, glutamate, orexin, and histamine levels, and indirectly decreases cerebral gamma-amino-butrytic acid levels. In addition to its approved use treating excessive somnolence, modafinil is thought to be used widely off-prescription for cognitive enhancement. However, despite this popularity, there has been little consensus on the extent and nature of the cognitive effects of modafinil in healthy, non-sleep-deprived humans. This problem is compounded by methodological discrepancies within the literature, and reliance on psychometric tests designed to detect cognitive effects in ill rather than healthy populations. In order to provide an up-to-date systematic evaluation that addresses these concerns, we searched MEDLINE with the terms "modafinil" and "cognitive", and reviewed all resultant primary studies in English from January 1990 until December 2014 investigating the cognitive actions of modafinil in healthy non-sleep-deprived humans. We found that whilst most studies employing basic testing paradigms show that modafinil intake enhances executive function, only half show improvements in attention and learning and memory, and a few even report impairments in divergent creative thinking. In contrast, when more complex assessments are used, modafinil appears to consistently engender enhancement of attention, executive functions, and learning. Importantly, we did not observe any preponderances for side effects or mood changes. Finally, in light of the methodological discrepancies encountered within this literature, we conclude with a series of recommendations on how to optimally detect valid, robust, and consistent effects in healthy populations that should aid future assessment of neuroenhancement.
Topics: Benzhydryl Compounds; Cognition; Humans; Modafinil; Nootropic Agents
PubMed: 26381811
DOI: 10.1016/j.euroneuro.2015.07.028 -
International Journal of Clinical... Dec 2014To describe the efficacy and safety of suvorexant for the treatment of insomnia. (Review)
Review
Suvorexant for insomnia: a systematic review of the efficacy and safety profile for this newly approved hypnotic - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed?
OBJECTIVE
To describe the efficacy and safety of suvorexant for the treatment of insomnia.
DATA SOURCES
The pivotal registration trials were accessed by querying http://www.ncbi.nlm.nih.gov/pubmed/ and http://www.clinicaltrials.gov for the search terms 'suvorexant' and 'MK4305'. Briefing documents from the US Food and Drug Administration Peripheral & Central Nervous System Drugs Advisory Committee and product labelling, provided additional information.
STUDY SELECTION
All available clinical reports of studies were identified.
DATA EXTRACTION
Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the available study reports and other sources of information.
DATA SYNTHESIS
Suvorexant (MK4305) is the first orexin receptor antagonist approved for the treatment of insomnia. This approval was based in part on a Phase 3 clinical development programme that included two similarly designed, 3-month, randomised, double-blind, placebo-controlled, parallel-group studies examining suvorexant 40 and 20 mg in non-elderly adults (age < 65 years) and 30 and 15 mg in elderly patients (age ≥ 65 years). Suvorexant was superior to placebo for sleep latency as assessed both objectively by polysomnography and subjectively by patient-estimated sleep latency; suvorexant was also superior to placebo for sleep maintenance, as assessed both objectively by polysomnography and subjectively by patient-estimated total sleep time. NNT vs. placebo for response as measured by a ≥ 6 point improvement on the Insomnia Severity Index at month 3 was 8 (95% CI 6-14) for both the higher and lower dose regimens. The most commonly encountered adverse event (incidence ≥ 5% and at least twice the rate of placebo) as identified in product labelling is somnolence, with NNH values vs. placebo of 13 (95% CI 11-18) for suvorexant 40 and 30 mg, and 28 (95% CI 17-82) for suvorexant 20 and 15 mg. The efficacy and tolerability profile of suvorexant is similar for those < 65 and ≥ 65 years of age. Rebound insomnia and withdrawal effects were not observed when suvorexant was discontinued after 3 months or after 12 months of nightly use. Because of concerns about dose-related, next-day effects, including sedation, the recommended dose range is 10-20 mg.
CONCLUSIONS
Suvorexant appears efficacious and relatively tolerable. Its different mechanism of action and potentially different safety and tolerability profile compared with currently available hypnotics represents a new option for the pharmacological treatment of insomnia.
Topics: Azepines; Drug Administration Schedule; Humans; Hypnotics and Sedatives; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Triazoles
PubMed: 25231363
DOI: 10.1111/ijcp.12568 -
BioMed Research International 2013There is a growing evidence that neuropeptides may be involved in the pathophysiology of suicidal behavior. A critical review of the literature was conducted to... (Meta-Analysis)
Meta-Analysis Review
There is a growing evidence that neuropeptides may be involved in the pathophysiology of suicidal behavior. A critical review of the literature was conducted to investigate the association between neuropeptides and suicidal behavior. Only articles from peer-reviewed journals were selected for the inclusion in the present review. Twenty-six articles were assessed for eligibility but only 22 studies were included. Most studies have documented an association between suicidality and some neuropeptides such as corticotropin-releasing factor (CRF), VGF, cholecystokinin, substance P, and neuropeptide Y (NPY), which have been demonstrated to act as key neuromodulators of emotional processing. Significant differences in neuropeptides levels have been found in those who have attempted or completed suicide compared with healthy controls or those dying from other causes. Despite cross-sectional associations between neuropeptides levels and suicidal behavior, causality may not be inferred. The implications of the mentioned studies were discussed in this review paper.
Topics: Arginine Vasopressin; Corticotropin-Releasing Hormone; Dynorphins; Galanin; Humans; Intracellular Signaling Peptides and Proteins; Neuropeptides; Orexins; Oxytocin; Substance P; Suicide
PubMed: 23986909
DOI: 10.1155/2013/687575