| 1. |
- Handke, Analena, et al.
(author)
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Acute inflammation and psychomotor slowing : Experimental assessment using lipopolysaccharide administration in healthy humans
- 2020
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In: Brain, Behavior, and Immunity - Health. - : Elsevier BV. - 2666-3546. ; 8
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Journal article (peer-reviewed)abstract
- Data from clinical and cross-sectional studies suggest that inflammation contributes to psychomotor slowing and attentional deficits found in depressive disorder. However, experimental evidence is still lacking. The aim of this study was to clarify the effect of inflammation on psychomotor slowing using an experimental and acute model of inflammation, in which twenty-two healthy volunteers received an intravenous injection of lipopolysaccharide (LPS, dose: 0.8 ng/kg body weight) and of placebo, in a randomized order following a double-blind within-subject crossover design. A reaction time test and a go/no-go test were conducted 3 h after the LPS/placebo injection and interleukin (IL)-6 and tumor necrosis factor (TNF)-α concentrations were assessed. No effect of experimental inflammation on reaction times or errors for either test was found. However, inflammation was related to worse self-rated performance and lower effort put in the tasks. Exploratory analyses indicated that reaction time fluctuated more over time during acute inflammation. These data indicate that acute inflammation has only modest effects on psychomotor speed and attention in healthy subjects objectively, but alters the subjective evaluation of test performance. Increased variability in reaction time might be the first objective sign of altered psychomotor ability and would merit further investigation.
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| 2. |
- Lasselin, Julie, et al.
(author)
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Comparison of bacterial lipopolysaccharide-induced sickness behavior in rodents and humans : Relevance for symptoms of anxiety and depression
- 2020
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In: Neuroscience and Biobehavioral Reviews. - : Elsevier BV. - 0149-7634 .- 1873-7528. ; 115, s. 15-24
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Research review (peer-reviewed)abstract
- Increasing evidence from animal and human studies suggests that inflammation may be involved in mood disorders. Sickness behavior and emotional changes induced by experimental inflammatory stimuli have been extensively studied in humans and rodents to better understand the mechanisms underlying inflammationdriven mood alterations. However, research in animals and humans have remained compartmentalized and a comprehensive comparison of inflammation-induced sickness and depressive-like behavior between rodents and humans is lacking. Thus, here, we highlight similarities and differences in the effects of bacterial lipopolysaccharide administration on the physiological (fever and cytokines), behavioral and emotional components of the sickness response in rodents and humans, and discuss the translational challenges involved. We also emphasize the differences between observable sickness behavior and subjective sickness reports, and advocate for the need to obtain both subjective reports and objective measurements of sickness behavior in humans. We aim to provide complementary insights for translational clinical and experimental research on inflammation-induced behavioral and emotional changes, and their relevance for mood disorders such as depression.
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| 3. |
- Lasselin, Julie, et al.
(author)
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Editorial: Clinical Relevance of the Immune-to-Brain and Brain-to-Immune Communications
- 2019
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In: Frontiers in Behavioral Neuroscience. - : Frontiers Media SA. - 1662-5153. ; 12
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Journal article (other academic/artistic)abstract
- Experimental and clinical evidence demonstrates an intense crosstalk among the nervous, endocrine and immune systems (Dantzer, 2018). The central nervous system (CNS) not only has the capacity to affect peripheral immune functions, but is also able to sense and process signals from the peripheral immune system. The bi-directional interaction between the CNS and the peripheral immune system has gained great interest as it can help better understanding disease pathophysiology to improve health and treatment outcomes in patients, and to understand how modifiable life-style factors can be associated with health. In this special issue of Frontiers in Behavioral Neuroscience, Frontiers in Immunology, and Frontiers in Neurology, we have collected original works and perspectives that provide new insights on the clinical relevance of immune-to-brain and brain-to-immune communications.
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| 4. |
- Lasselin, Julie, et al.
(author)
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Fatigue and sleepiness responses to experimental inflammation and exploratory analysis of the effect of baseline inflammation in healthy humans
- 2020
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In: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 83, s. 309-314
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Journal article (peer-reviewed)abstract
- Inflammation is believed to be a central mechanism in the pathophysiology of fatigue. While it is likely that dynamic of the fatigue response after an immune challenge relates to the corresponding cytokine release, this lacks evidence. Although both fatigue and sleepiness are strong signals to rest, they constitute distinct symptoms which are not necessarily associated, and sleepiness in relation to inflammation has been rarely investigated. Here, we have assessed the effect of an experimental immune challenge (administration of lipopolysaccharide, LPS) on the development of both fatigue and sleepiness, and the associations between increases in cytokine concentrations, fatigue and sleepiness, in healthy volunteers. In addition, because chronic-low grade inflammation may represent a risk factor for fatigue, we tested whether higher baseline levels of inflammation result in a more pronounced development of cytokine-induced fatigue and sleepiness. Data from four experimental studies was combined, giving a total of 120 subjects (LPS N = 79, 18 (23%) women; Placebo N = 69, 12 (17%) women). Administration of LPS resulted in a stronger increase in fatigue and sleepiness compared to the placebo condition, and the development of both fatigue and sleepiness closely paralleled the cytokine responses. Individuals with stronger increases in cytokine concentrations after LPS administration also suffered more from fatigue and sleepiness (N = 75), independent of gender. However, there was no support for the hypothesis that higher baseline inflammatory markers moderated the responses in fatigue or sleepiness after an inflammatory challenge. The results demonstrate a tight connection between the acute inflammatory response and development of both fatigue and sleepiness, and motivates further investigation of the involvement of inflammation in the pathophysiology of central fatigue.
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| 5. |
- Lasselin, Julie, 1986-, et al.
(author)
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Guest Editorial: The inner immune voice : Can we explicitly sense antibody response to Covid-19 vaccination?
- 2023
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In: Biological Psychology. - : Elsevier. - 0301-0511 .- 1873-6246. ; 182
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Journal article (other academic/artistic)abstract
- Interoception refers to the sensing, interpreting, and integration of signals coming from the body (i.e., interoceptive signals) by the nervous system (Allen, 2020, Khalsa et al., 2018). Alterations in the processing of interoceptive signals is believed to significantly play a role in the development of mental health conditions (Barrett, 2017, Khalsa et al., 2018), and the methodology for human interoception research is expanding (Garfinkel et al., 2022). Investigations in the field have mostly been restricted to the domain of cardiovascular signals, as well as to the respiratory and gastrointestinal axes (Benson et al., 2012, Garfinkel et al., 2016, Khalsa and Lapidus, 2016). The reason is most likely that humans' appraisal of the status of these signals are commonly explicit and frequently occurring, and due to the fact that the assessment of perceptual alterations in interoceptive awareness (i.e., interoceptive attention, accuracy, intensity, sensibility, and insight) of these signals is convenient. There is less consensus regarding whether other types of bodily signals, such as the status of other organs or various hormonal levels, are reachable in an explicit manner. The study by Dimitroff et al. (2023) suggests, for the first time, that we humans can perhaps explicitly estimate our actual immune response.
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| 6. |
- Lasselin, Julie, et al.
(author)
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Immunological and behavioral responses to in vivo lipopolysaccharide administration in young and healthy obese and normal-weight humans
- 2020
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In: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 88, s. 283-293
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Journal article (peer-reviewed)abstract
- Obesity is associated with an increase prevalence of neuropsychiatric symptoms and diseases, such as depression. Based on the facts that pro-inflammatory cytokines are able to modulate behavior, and that obesity is characterized by a chronic low-grade inflammatory state, inflammation has been hypothesized to contribute to the neuropsychiatric comorbidity in obese individuals. However, a causal link between inflammation and the development of neuropsychiatric symptoms is hard to establish in humans. Here, we used an inflammatory stimulus, i.e. the intravenous injection of lipopolysaccharide (LPS), in a double-blind placebo-controlled design, to determine the vulnerability of obese individuals to inflammation-induced behavioral changes. The hypothesis was that obese individuals would show heightened behavioral response compared to normal-weight subjects for the same inflammatory stimulus, reflecting an increased sensitivity to the behavioral effects of pro-inflammatory cytokines. LPS (dose 0.8 ng/kg body weight, adjusted for estimated blood volume in obese subjects) and placebo (saline) were intravenously injected in 14 obese healthy subjects and 23 normal-weight healthy subjects in a within-subject, randomized, crossover design. LPS administration induced, in both groups, an acute increase in blood concentrations of cytokines (interleukin-6, tumor necrosis factor-alpha, and IL-10), as well as in body temperature, cortisol, norepinephrine, sickness symptoms, fatigue, negative mood, and state anxiety. There were little differences in the immune and behavioral responses to LPS between obese and normal-weight subjects, but the cortisol response to LPS was strongly attenuated in obese individuals. Higher percentage of body fat was related to a lower cortisol response to LPS. Taken together, the population of young and healthy obese individuals in this study did not exhibit an increased behavioral sensitivity to cytokines, but an attenuated cortisol response to the immune challenge. Future studies will need to determine whether additional physiological and psychological factors interact with the state of obesity to increase the risk for inflammation-induced neuropsychiatric symptoms.
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| 7. |
- Lasselin, Julie, et al.
(author)
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Mood disturbance during experimental endotoxemia : Predictors of state anxiety as a psychological component of sickness behavior
- 2016
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In: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 57, s. 30-37
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Journal article (peer-reviewed)abstract
- Lipopolysaccharide (LPS) administration is a well-established model to assess afferent immune-to-brain communication and behavioral aspects of inflammation. Nevertheless, only few studies in comparatively small samples have assessed state anxiety as a psychological component of sickness behavior despite possible clinical implications for the pathophysiology of neuropsychiatric conditions. Thus, the goal of the present analyses carried out in a large, pooled dataset from two independent study sites was to analyze the state anxiety response to LPS administration and to investigate predictors (i.e., cytokine changes; pre-existing anxiety and depression symptoms assessed with the Hospital Anxiety and Depression Scale) of the LPS-induced state anxiety changes at different time points after LPS administration. Data from 186 healthy volunteers who participated in one of six randomized, placebo-controlled human studies involving intravenous administration of LPS at doses of 0.4-0.8ng/kg body weight were combined. State anxiety as well as circulating interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-10 concentrations were significantly increased 2h and 3h after LPS administration, with a peak at 2h, and returned to baseline 6h after administration. Greater changes in IL-6 from baseline to 3h after LPS administration significantly and independently predicted a more pronounced LPS-induced state anxiety response. In addition, higher pre-existing subclinical anxiety symptoms significantly predicted a lower increase in state anxiety 3h and 6h after LPS-administration, which was mediated by TNF-α changes. In conclusion, our findings give additional support for a putative role of inflammatory mechanisms in the pathophysiology of stress-related and anxiety disorders and give new insight on the potential role of pre-existing subclinical affective symptoms.
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| 8. |
- Lasselin, Julie, et al.
(author)
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Sick for science : experimental endotoxemia as a translational tool to develop and test new therapies for inflammation-associated depression
- 2020
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In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 3672-3683
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Journal article (peer-reviewed)abstract
- Depression is one of the global leading causes of disability, but treatments remain limited and classical antidepressants were found to be ineffective in a substantial proportion of patients. Thus, novel effective therapies for the treatment of depression are urgently needed. Given the emerging role of inflammation in the etiology and pathophysiology of affective disorders, we herein illustrate how experimental endotoxemia, a translational model of systemic inflammation, could be used as a tool to develop and test new therapeutic options against depression. Our concept is based on the striking overlap of inflammatory, neural, and affective characteristics in patients with inflammation-associated depression and in endotoxin-challenged healthy subjects. Experimental administration of endotoxin in healthy volunteers is safe, well-tolerated, and without known long-term health risks. It offers a highly standardized translational approach to characterize potential targets of therapies against inflammation-associated depression, as well as to identify characteristics of patients that would benefit from these interventions, and, therefore, could contribute to improve personalization of treatment and to increase the overall rate of responders.
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| 9. |
- Månsson, Kristoffer N. T., et al.
(author)
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Anterior insula morphology and vulnerability to psychopathology-related symptoms in response to acute inflammation
- 2022
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In: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 99, s. 9-16
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Journal article (peer-reviewed)abstract
- Introduction: The role of inflammation in common psychiatric diseases is now well acknowledged. However, the factors and mechanisms underlying inter-individual variability in the vulnerability to develop psychopathology related symptoms in response to inflammation are not well characterized. Herein, we aimed at investigating morphological brain regions central for interoception and emotion regulation, and if these are associated with acute inflammation-induced sickness and anxiety responses.Methods: Systemic inflammation was induced using an intravenous injection of lipopolysaccharide (LPS) at a dose of 0.6 ng/kg body weight in 28 healthy individuals, while 21 individuals received an injection of saline (placebo). Individuals' gray matter volume was investigated by automated voxel-based morphometry technique on T1-weighted anatomical images derived from magnetic resonance imaging (MRI). Plasma concentrations of TNF alpha and IL-6, sickness symptoms (SicknessQ), and state anxiety (STAI-S) were measured before and after the injection.Results: A stronger sickness response to LPS was significantly associated with a larger anterior insula gray matter volume, independently from increases in cytokine concentrations, age, sex and body mass index (R-2 = 65.6%). Similarly, a greater LPS-induced state anxiety response was related to a larger anterior insula gray matter volume, and also by a stronger increase in plasma TNF-alpha concentrations (R-2 = 40.4%).Discussion: Anterior insula morphology appears central in the sensitivity to develop symptoms of sickness and anxiety in response to inflammation, and could thus be one risk factor in inflammation-related psychopathologies. Because of the limited sample size, the current results need to be replicated.
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