| 1. |
- Sjörs Dahlman, Anna, 1981-, et al.
(författare)
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The hypothalamo–pituitary–adrenal axis and the autonomic nervous system in burnout
- 2021
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Ingår i: Handbook of Clinical Neurology. - : Elsevier B.V.. - 0072-9752. ; , s. 83-94, s. 83-94
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Burnout constitutes a serious health concern in the modern working environment. It is a stress-related condition that has developed as a result of a prolonged psychosocial stress exposure causing a persistent mismatch between demands and resources. The main symptom is emotional exhaustion, but physical fatigue, diminished professional efficacy, cynicism, and cognitive impairments are also associated with this condition. Burnout has been used both as a psychologic term in occupational settings and as a clinical diagnosis in patient populations, and there is currently no universally accepted definition and diagnostic criteria of burnout. It has been hypothesized that the two main stress response systems, the autonomic nervous system (ANS) and the hypothalamus–pituitary–adrenal axis (HPA axis), are involved in the pathogenesis of burnout. A common hypothesis is that in the early stages of chronic stress, the HPA axis and sympathetic ANS activity tend to be higher, while it will decrease with a longer duration of chronic stress to ultimately reach a state of hypoactivity in clinical burnout. The current research in this field shows many contradictory results. Thus there is no compelling evidence of either ANS or HPA dysfunction in burnout. However, there is partial support for the hypothesis of HPA and sympathetic hyperactivity in early stages, and HPA hyporeactivity and low vagal activity in more severe burnout cases, but high-quality studies investigating the causal links are still lacking. © 2021 Elsevier B.V.
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| 2. |
- Anderberg, Rozita H, 1976, et al.
(författare)
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GLP-1 is both anxiogenic and antidepressant; divergent effects of acute and chronic GLP-1 on emotionality.
- 2016
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 65, s. 54-66
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Tidskriftsartikel (refereegranskat)abstract
- Glucagon-like peptide 1 (GLP-1), produced in the intestine and hindbrain, is known for its glucoregulatory and appetite suppressing effects. GLP-1 agonists are in clinical use for treatment of type 2 diabetes and obesity. GLP-1, however, may also affect brain areas associated with emotionality regulation. Here we aimed to characterize acute and chronic impact of GLP-1 on anxiety and depression-like behavior. Rats were subjected to anxiety and depression behavior tests following acute or chronic intracerebroventricular or intra-dorsal raphe (DR) application of GLP-1 receptor agonists. Serotonin or serotonin-related genes were also measured in the amygdala, DR and the hippocampus. We demonstrate that both GLP-1 and its long lasting analog, Exendin-4, induce anxiety-like behavior in three rodent tests of this behavior: black and white box, elevated plus maze and open field test when acutely administered intraperitoneally, into the lateral ventricle, or directly into the DR. Acute central GLP-1 receptor stimulation also altered serotonin signaling in the amygdala. In contrast, chronic central administration of Exendin-4 did not alter anxiety-like behavior but significantly reduced depression-like behavior in the forced swim test. Importantly, this positive effect of Exendin-4 was not due to significant body weight loss and reduced food intake, since rats pair-fed to Exendin-4 rats did not show altered mood. Collectively we show a striking impact of central GLP-1 on emotionality and the amygdala serotonin signaling that is divergent under acute versus chronic GLP-1 activation conditions. We also find a novel role for the DR GLP-1 receptors in regulation of behavior. These results may have direct relevance to the clinic, and indicate that Exendin-4 may be especially useful for obese patients manifesting with comorbid depression.
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| 3. |
- Anderberg, Rozita H, 1976, et al.
(författare)
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Glucagon-Like Peptide 1 and Its Analogs Act in the Dorsal Raphe and Modulate Central Serotonin to Reduce Appetite and Body Weight
- 2017
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 66:4, s. 1062-1073
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Tidskriftsartikel (refereegranskat)abstract
- Glucagon-like peptide 1 (GLP-1) and serotonin play critical roles in energy balance regulation. Both systems are exploited clinically as antiobesity strategies. Surprisingly, whether they interact in order to regulate energy balance is poorly understood. Here we investigated mechanisms by which GLP-1 and serotonin interact at the level of the central nervous system. Serotonin depletion impaired the ability of exendin-4, a clinically used GLP-1 analog, to reduce body weight in rats, suggesting that serotonin is a critical mediator of the energy balance impact of GLP-1 receptor (GLP-1R) activation. Serotonin turnover and expression of 5-hydroxytryptamine (5-HT) 2A (5-HT2A) and 5-HT2C serotonin receptors in the hypothalamus were altered by GLP-1R activation. We demonstrate that the 5-HT2A, but surprisingly not the 5-HT2C, receptor is critical for weight loss, anorexia, and fat mass reduction induced by central GLP-1R activation. Importantly, central 5-HT2A receptors are also required for peripherally injected liraglutide to reduce feeding and weight. Dorsal raphe (DR) harbors cell bodies of serotonin-producing neurons that supply serotonin to the hypothalamic nuclei. We show that GLP-1R stimulation in DR is sufficient to induce hypophagia and increase the electrical activity of the DR serotonin neurons. Finally, our results disassociate brain metabolic and emotionality pathways impacted by GLP-1R activation. This study identifies serotonin as a new critical neural substrate for GLP-1 impact on energy homeostasis and expands the current map of brain areas impacted by GLP-1R activation.
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| 4. |
- Anderberg, Rozita H, 1976, et al.
(författare)
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The Stomach-Derived Hormone Ghrelin Increases Impulsive Behavior.
- 2016
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Ingår i: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 1740-634X. ; 14, s. 1199-1209
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Tidskriftsartikel (refereegranskat)abstract
- Impulsivity, defined as impaired decision making, is associated with many psychiatric and behavioral disorders, such as attention-deficit/hyperactivity disorder as well as eating disorders. Recent data indicate that there is a strong positive correlation between food reward behavior and impulsivity, but the mechanisms behind this relationship remain unknown. Here we hypothesize that ghrelin, an orexigenic hormone produced by the stomach and known to increase food reward behavior, also increases impulsivity. In order to assess the impact of ghrelin on impulsivity, rats were trained in three complementary tests of impulsive behavior and choice: differential reinforcement of low rate (DRL), go/no-go, and delay discounting. Ghrelin injection into the lateral ventricle increased impulsive behavior, as indicated by reduced efficiency of performance in the DRL test, and increased lever pressing during the no-go periods of the go/no-go test. Central ghrelin stimulation also increased impulsive choice, as evidenced by the reduced choice for large rewards when delivered with a delay in the delay discounting test. In order to determine whether signaling at the central ghrelin receptors is necessary for maintenance of normal levels of impulsive behavior, DRL performance was assessed following ghrelin receptor blockade with central infusion of a ghrelin receptor antagonist. Central ghrelin receptor blockade reduced impulsive behavior, as reflected by increased efficiency of performance in the DRL task. To further investigate the neurobiological substrate underlying the impulsivity effect of ghrelin, we microinjected ghrelin into the ventral tegmental area, an area harboring dopaminergic cell bodies. Ghrelin receptor stimulation within the VTA was sufficient to increase impulsive behavior. We further evaluated the impact of ghrelin on dopamine-related gene expression and dopamine turnover in brain areas key in impulsive behavior control. This study provides the first demonstration that the stomach-produced hormone ghrelin increases impulsivity and also indicates that ghrelin can change two major components of impulsivity-motor and choice impulsivity.Neuropsychopharmacology advance online publication, 21 October 2015; doi:10.1038/npp.2015.297.
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| 5. |
- Dickson, Suzanne L., 1966, et al.
(författare)
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Blockade of central nicotine acetylcholine receptor signaling attenuate ghrelin-induced food intake in rodents.
- 2010
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Ingår i: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 171:4, s. 1180-1186
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Tidskriftsartikel (refereegranskat)abstract
- Here we sought to determine whether ghrelin's central effects on food intake can be interrupted by nicotinic cholinergic receptor (nAChR) blockade. Ghrelin regulates mesolimbic dopamine neurons projecting from the ventral tegmental area (VTA) to the nucleus accumbens (NAcc), partly via cholinergic VTA afferents originating in the laterodorsal tegmental area (LDTg). Given that these cholinergic projections to the VTA have been implicated in natural as well as drug-induced reinforcement, we sought to investigate the role of cholinergic signaling in ghrelin-induced food intake as well as fasting-induced food intake, for which endogenous ghrelin has been implicated. We found that i.p. treatment with the non-selective centrally active nAChR antagonist, mecamylamine decreased fasting-induced food intake in both mice and rats. Moreover, central administration of mecamylamine decreased fasting-induced food intake in rats. I.c.v. ghrelin-induced food intake was suppressed by mecamylamine but not by hexamethonium, a peripheral nAChR antagonist. Furthermore, mecamylamine i.p. blocked food intake following ghrelin injection into the VTA. Expression of the ghrelin receptor, the growth hormone secretagogue receptor 1A (GHS-R1A), was found to co-localize with choline acetyltransferase (ChAT), a marker of cholinergic neurons, in the LDTg. Finally, mecamylamine i.p. treatment decreased the ability of palatable food to condition a place preference. These data suggest that ghrelin-induced food intake is partly mediated via nAChRs and that nicotinic blockade decreases the rewarding properties of food.
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| 6. |
- Dickson, Suzanne L., 1966, et al.
(författare)
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The glucagon-like peptide 1 (GLP-1) analogue, exendin-4, decreases the rewarding value of food: a new role for mesolimbic GLP-1 receptors.
- 2012
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Ingår i: The Journal of neuroscience : the official journal of the Society for Neuroscience. - 1529-2401. ; 32:14, s. 4812-20
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Tidskriftsartikel (refereegranskat)abstract
- The glucagon-like peptide 1 (GLP-1) system is a recently established target for type 2 diabetes treatment. In addition to regulating glucose homeostasis, GLP-1 also reduces food intake. Previous studies demonstrate that the anorexigenic effects of GLP-1 can be mediated through hypothalamic and brainstem circuits which regulate homeostatic feeding. Here, we demonstrate an entirely novel neurobiological mechanism for GLP-1-induced anorexia in rats, involving direct effects of a GLP-1 agonist, Exendin-4 (EX4) on food reward that are exerted at the level of the mesolimbic reward system. We assessed the impact of peripheral, central, and intramesolimbic EX4 on two models of food reward: conditioned place preference (CPP) and progressive ratio operant-conditioning. Food-reward behavior was reduced in the CPP test by EX4, as rats no longer preferred an environment previously paired to chocolate pellets. EX4 also decreased motivated behavior for sucrose in a progressive ratio operant-conditioning paradigm when administered peripherally. We show that this effect is mediated centrally, via GLP-1 receptors (GLP-1Rs). GLP-1Rs are expressed in several key nodes of the mesolimbic reward system; however, their function remains unexplored. Thus we sought to determine the neurobiological substrates underlying the food-reward effect. We found that the EX4-mediated inhibition of food reward could be driven from two key mesolimbic structures-ventral tegmental area and nucleus accumbens-without inducing concurrent malaise or locomotor impairment. The current findings, that activation of central GLP-1Rs strikingly suppresses food reward/motivation by interacting with the mesolimbic system, indicate an entirely novel mechanism by which the GLP-1R stimulation affects feeding-oriented behavior.
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| 7. |
- Egecioglu, Emil, 1977, et al.
(författare)
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Central NMU signaling in body weight and energy balance regulation: evidence from NMUR2 deletion and chronic central NMU treatment in mice.
- 2009
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Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 297:3
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the role of the central neuromedin U (NMU) signaling system in body weight and energy balance regulation, we examined the effects of long-term intracerebroventricular (icv) infusion of NMU in C57Bl/6 mice and in mice lacking the gene encoding NMU receptor 2. In diet-induced obese male and female C57BL/6 mice, icv infusion of NMU (8 microg x day(-1) x mouse(-1)) for 7 days decreased body weight and total energy intake compared with vehicle treatment. However, these parameters were unaffected by NMU treatment in lean male and female C57BL/6 mice fed a standard diet. In addition, female (but not male) NMUR2-null mice had increased body weight and body fat mass when fed a high-fat diet but lacked a clear body weight phenotype when fed a standard diet compared with wild-type littermates. Furthermore, female (but not male) NMUR2-null mice fed a high-fat diet were protected from central NMU-induced body weight loss compared with littermate wild-type mice. Thus, we provide the first evidence that long-term central NMU treatment reduces body weight, food intake, and adiposity and that central NMUR2 signaling is required for these effects in female but not male mice.
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| 8. |
- Egecioglu, Emil, 1977, et al.
(författare)
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Hedonic and incentive signals for body weight control.
- 2011
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Ingår i: Reviews in endocrine & metabolic disorders. - : Springer Science and Business Media LLC. - 1573-2606 .- 1389-9155. ; 12:3, s. 141-51
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Forskningsöversikt (refereegranskat)abstract
- Here we review the emerging neurobiological understanding of the role of the brain's reward system in the regulation of body weight in health and in disease. Common obesity is characterized by the over-consumption of palatable/rewarding foods, reflecting an imbalance in the relative importance of hedonic versus homeostatic signals. The popular 'incentive salience theory' of food reward recognises not only a hedonic/pleasure component ('liking') but also an incentive motivation component ('wanting' or 'reward-seeking'). Central to the neurobiology of the reward mechanism is the mesoaccumbal dopamine system that confers incentive motivation not only for natural rewards such as food but also by artificial rewards (eg. addictive drugs). Indeed, this mesoaccumbal dopamine system receives and integrates information about the incentive (rewarding) value of foods with information about metabolic status. Problematic over-eating likely reflects a changing balance in the control exerted by hypothalamic versus reward circuits and/or it could reflect an allostatic shift in the hedonic set point for food reward. Certainly, for obesity to prevail, metabolic satiety signals such as leptin and insulin fail to regain control of appetitive brain networks, including those involved in food reward. On the other hand, metabolic control could reflect increased signalling by the stomach-derived orexigenic hormone, ghrelin. We have shown that ghrelin activates the mesoaccumbal dopamine system and that central ghrelin signalling is required for reward from both chemical drugs (eg alcohol) and also from palatable food. Future therapies for problematic over-eating and obesity may include drugs that interfere with incentive motivation, such as ghrelin antagonists.
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| 9. |
- Eklof, B., et al.
(författare)
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The role of self-reported stressors in recovery from Exhaustion Disorder: a longitudinal study
- 2022
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Ingår i: Bmc Psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background Exhaustion disorder (ED) is a stress-induced disorder characterized by physical and mental symptoms of exhaustion that can be long-lasting. Although stress exposure is essential for the development of ED, little is known regarding the role of stressors in the maintenance of ED. The aim of the study was to investigate the role of work-related stressors, private-related stressors, and adverse childhood experiences in long-term recovery from ED. Methods A mixed methods design was used. The design was sequential, and data analysis was performed in two parts, where the first part consisted of qualitative analysis of patient records, and the second part consisted of statistical analysis of the data retrieved from the qualitative coding. Patient records from 150 patients with ED was analysed regarding work-related stressors, private-related stressors, and adverse childhood experiences. For each patient, two patient records were analysed, one from the time of diagnosis (baseline) and one from the follow-up clinical assessment, 7-12 years after diagnosis (follow-up). Out of the 150 patients, 51 individuals still fulfilled the diagnostic criteria for ED at follow-up (ED group) and 99 individuals no longer fulfilled the diagnostic criteria and were thus considered recovered (EDrec). Percentages in each group (ED and EDrec) reporting each stressor at baseline and follow-up were calculated as well as the differences in percentage points between the groups along with the 95% confidence intervals for the differences. Results At baseline, significantly more EDrec patients reported quantitative demands (73% EDrec, 53% ED) and managerial responsibilities (14% EDrec, 2% ED). Private-related stressors did not differ at baseline. At follow-up, significantly more ED patients reported managerial responsibilities (8 ED, 0% EDrec) and caregiver stress (child) (24% ED, 6% EDrec) and significantly more EDrec patients reported caregiver stress (parent) (6% EDrec, 0% ED). There were no differences regarding adverse childhood experiences. Conclusions The main conclusion is that neither adverse childhood experiences nor any of the stressors at baseline are associated with long-term ED. Ongoing stressors related to having responsibility for other people, such as managerial responsibilities or caring for a child with a chronic disease or psychiatric disorder, may be associated with long-term exhaustion.
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| 10. |
- Hansson, Caroline, 1981, et al.
(författare)
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A possible association between panic disorder and a polymorphism in the preproghrelin gene
- 2013
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Ingår i: Psychiatry Research. - : Elsevier. - 0165-1781 .- 1872-7123. ; 206:1, s. 22-25
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to investigate whether polymorphisms in the preproghrelin gene are associated with anxiety disorders, such as panic disorder, in humans. Panic disorder is a severe anxiety disorder, characterized by sudden attacks of intense fear or anxiety in combination with somatic symptoms. The preproghrelin gene codes for two gut-derived circulating peptides that have been linked to anxiety-like behaviour in rodents: ghrelin (an orexigenic, pro-obesity hormone) and obestatin. In the present study, we genotyped three missense mutations in the preproghrelin gene in 215 patients suffering from panic disorder and in 451 controls. The A allele of the rs4684677 polymorphism was significantly associated with panic disorder, while there were no significant associations with the two other polymorphisms studied. We conclude that the rs4684677 (Gln90Leu) polymorphism in the preproghrelin gene may be associated with increased risk of panic disorder. It will be important to confirm these findings in additional panic disorder patient groups.
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