The predictive validity of a Brain Care Score for late-life depression and a composite outcome of dementia, stroke, and late-life depression: data from the UK Biobank cohort.

Introduction: The 21-point Brain Care Score (BCS) is a novel tool designed to motivate individuals and care providers to take action to reduce the risk of stroke and dementia by encouraging lifestyle changes. Given that late-life depression is increasingly recognized to share risk factors with stroke and dementia, and is an important clinical endpoint for brain health, we tested the hypothesis that a higher BCS is associated with a reduced incidence of future depression. Additionally, we examined its association with a brain health composite outcome comprising stroke, dementia, and late-life depression. Methods: The BCS was derived from the United Kingdom Biobank baseline evaluation in participants with complete data on BCS items. Associations of BCS with the risk of subsequent incident late-life depression and the composite brain health outcome were estimated using multivariable Cox proportional hazard models. These models were adjusted for age at baseline and sex assigned at birth. Results: A total of 363,323 participants were included in this analysis, with a median BCS at baseline of 12 (IQR: 11-14). There were 6,628 incident cases of late-life depression during a median follow-up period of 13 years. Each five-point increase in baseline BCS was associated with a 33% lower risk of incident late-life depression (95% CI: 29%-36%) and a 27% lower risk of the incident composite outcome (95% CI: 24%-30%). Discussion: These data further demonstrate the shared risk factors across depression, dementia, and stroke. The findings suggest that a higher BCS, indicative of healthier lifestyle choices, is significantly associated with a lower incidence of late-life depression and a composite brain health outcome. Additional validation of the BCS is warranted to assess the weighting of its components, its motivational aspects, and its acceptability and adaptability in routine clinical care worldwide.

Diagnostic and demographic factors of pediatric and adult catatonia hospitalizations: A 2016-2020 National Inpatient Sample Study.

OBJECTIVE: Catatonia is a neuropsychiatric disorder that can occur in patients of any age, but it is uncertain whether patient demographics or underlying diagnoses differ between pediatric and adult patients. This study investigates patients of all ages diagnosed with catatonia during acute care hospitalizations in the United States over a 5-year period. METHOD: The National Inpatient Sample, an all-payors database of acute care hospital discharges, was queried for patients with a discharge diagnosis of catatonia between 2016 and 2020 with patients stratified by age as pediatric (≤18 years) or adult (>18 years). RESULTS: Among 174,776,205 hospitalizations recorded in the NIS from 2016 to 2020, 61,990 (95% CI: 60,257 to 63,723; 0.035%) involved a diagnosis of catatonia. Of these, 3255 were for pediatric patients and 58,735 were for adult patients. Compared with adult patients, pediatric catatonia patients were more likely to be male and non-White. Diagnostically, psychotic disorders, encephalitis, and neurodevelopmental disorders were more common primary discharge diagnoses in pediatric patients, while adult patients more frequently were diagnosed with mood disorders. Length of stay was not significantly different between pediatric and adult catatonia hospitalizations. Physical restraints were commonly applied for patients with catatonia. CONCLUSION: Pediatric and adult catatonia patients differed in sex, race, and diagnosis, although hospital length of stay was not different between pediatric and adult catatonia hospitalizations. These results may inform catatonia diagnosis in the hospital setting and point to disparities that could be targets of quality improvement efforts.

Brain Care Score and Neuroimaging Markers of Brain Health in Asymptomatic Middle-Age Persons.

OBJECTIVES: To investigate associations between health-related behaviors as measured using the Brain Care Score (BCS) and neuroimaging markers of white matter injury. METHODS: This prospective cohort study in the UK Biobank assessed the BCS, a novel tool designed to empower patients to address 12 dementia and stroke risk factors. The BCS ranges from 0 to 21, with higher scores suggesting better brain care. Outcomes included white matter hyperintensities (WMH) volume, fractional anisotropy (FA), and mean diffusivity (MD) obtained during 2 imaging assessments, as well as their progression between assessments, using multivariable linear regression adjusted for age and sex. RESULTS: We included 34,509 participants (average age 55 years, 53% female) with no stroke or dementia history. At first and repeat imaging assessments, every 5-point increase in baseline BCS was linked to significantly lower WMH volumes (25% 95% CI [23%-27%] first, 33% [27%-39%] repeat) and higher FA (18% [16%-20%] first, 22% [15%-28%] repeat), with a decrease in MD (9% [7%-11%] first, 10% [4%-16%] repeat). In addition, a higher baseline BCS was associated with a 10% [3%-17%] reduction in WMH progression and FA decline over time. DISCUSSION: This study extends the impact of the BCS to neuroimaging markers of clinically silent cerebrovascular disease. Our results suggest that improving one's BCS could be a valuable intervention to prevent early brain health decline.

Effects of Aerobic Exercise on Brain Age and Health in Middle-Aged and Older Adults: A Single-Arm Pilot Clinical Trial.

BACKGROUNDS: Sleep disturbances are prevalent among elderly individuals. While polysomnography (PSG) serves as the gold standard for sleep monitoring, its extensive setup and data analysis procedures impose significant costs and time constraints, thereby restricting the long-term application within the general public. Our laboratory introduced an innovative biomarker, utilizing artificial intelligence algorithms applied to PSG data to estimate brain age (BA), a metric validated in cohorts with cognitive impairments. Nevertheless, the potential of exercise, which has been a recognized means of enhancing sleep quality in middle-aged and older adults to reduce BA, remains undetermined. METHODS: We conducted an exploratory study to evaluate whether 12 weeks of moderate-intensity exercise can improve cognitive function, sleep quality, and the brain age index (BAI), a biomarker computed from overnight sleep electroencephalogram (EEG), in physically inactive middle-aged and older adults. Home wearable devices were used to monitor heart rate and overnight sleep EEG over this period. The NIH Toolbox Cognition Battery, in-lab overnight polysomnography, cardiopulmonary exercise testing, and a multiplex cytokines assay were employed to compare pre- and post-exercise brain health, exercise capacity, and plasma proteins. RESULTS: In total, 26 participants completed the initial assessment and exercise program, and 24 completed all procedures. Data are presented as mean [lower 95% CI of mean, upper 95% CI of mean]. Participants significantly increased maximal oxygen consumption (Pre: 21.11 [18.98, 23.23], Post 22.39 [20.09, 24.68], mL/kg/min; effect size: -0.33) and decreased resting heart rate (Pre: 66.66 [63.62, 67.38], Post: 65.13 [64.25, 66.93], bpm; effect size: -0.02) and sleeping heart rate (Pre: 64.55 [61.87, 667.23], Post: 62.93 [60.78, 65.09], bpm; effect size: -0.15). Total cognitive performance (Pre: 111.1 [107.6, 114.6], Post: 115.2 [111.9, 118.5]; effect size: 0.49) was significantly improved. No significant differences were seen in BAI or measures of sleep macro- and micro-architecture. Plasma IL-4 (Pre: 0.24 [0.18, 0.3], Post: 0.33 [0.24, 0.42], pg/mL; effect size: 0.49) was elevated, while IL-8 (Pre: 5.5 [4.45, 6.55], Post: 4.3 [3.66, 5], pg/mL; effect size: -0.57) was reduced. CONCLUSIONS: Cognitive function was improved by a 12-week moderate-intensity exercise program in physically inactive middle-aged and older adults, as were aerobic fitness (VO2max) and plasma cytokine profiles. However, we found no measurable effects on sleep architecture or BAI. It remains to be seen whether a study with a larger sample size and more intensive or more prolonged exercise exposure can demonstrate a beneficial effect on sleep quality and brain age.

Catatonia.

Catatonia is a neuropsychiatric disorder characterized by motor, affective and cognitive-behavioural signs, which lasts from hours to days. Intensive research over the past two decades has led to catatonia being recognized as an independent diagnosis in the International Classification of Diseases, 11th Revision (ICD-11) since 2022. Catatonia is found in 5-18% of inpatients on psychiatric units and 3.3% of inpatients on medical units. However, in an unknown number of patients, catatonia remains unrecognized and these patients are at risk of life-threatening complications. Hence, recognizing the symptoms of catatonia early is crucial to initiate appropriate treatment to achieve a favourable outcome. Benzodiazepines such as lorazepam and diazepam, electroconvulsive therapy, and N-methyl-D-aspartate antagonists such as amantadine and memantine, are the cornerstones of catatonia therapy. In addition, dopamine-modulating second-generation antipsychotics (for example, clozapine and aripiprazole) are effective in some patient populations. Early and appropriate treatment combined with new screening assessments has the potential to reduce the high morbidity and mortality associated with catatonia in psychiatric and non-psychiatric settings.

The effectiveness of the lorazepam challenge test in pediatric catatonia: A multisite retrospective cohort study.

OBJECTIVE: Catatonia is a neuropsychiatric disorder associated with changes in behavior and affect. In adults, catatonia can respond rapidly to treatment with benzodiazepines as part of the "lorazepam challenge test." The acute effectiveness of benzodiazepine treatment in pediatric catatonia, however, has received less study. This study reports catatonia severity as measured by the Bush Francis Catatonia Rating Scale (BFCRS) in pediatric patients before and after treatment with lorazepam. METHODS: Multicenter retrospective cohort study from 1/1/2018 to 6/1/2023 of patients aged 18 and younger with a clinical diagnosis of catatonia and assessment using the BFCRS before and after treatment with lorazepam. RESULTS: Among 54 patients, median age was 16, and 26 (48.1 %) were female. Neurodevelopmental disabilities were present in 24 (44.4 %) of patients. Prior to treatment, patients had a mean BFCRS score of 16.6 ± 6.1, which significantly reduced to 9.5 ± 5.3 following treatment with lorazepam (mean paired difference 7.1; t = 9.0, df = 53, p < 0.001), representing a large effect size (Hedges's g = 1.20; 95 % CI: 0.85 to 1.55). No significant association was found between lorazepam dose or route of administration and clinical response, nor were age, sex, study site, the presence of a neurodevelopmental disorder, the presence of hyperactive catatonic features, or the time between treatment and reassessment associated with post-treatment BFCRS. CONCLUSIONS: Lorazepam resulted in a rapid improvement in BFCRS score in pediatric patients, with a large effect size. Further research is needed into optimal dosing and route of administration of the lorazepam challenge test in pediatric patients.

Exploring the Trajectory of Catatonia in Neurodiverse and Neurotypical Pediatric Hospitalizations: A Multicenter Longitudinal Analysis.

Objective: Catatonia is a neuropsychiatric disorder that occurs in pediatric patients with a range of associated medical, psychiatric, and neurodevelopmental disorders (NDDs). This study describes hospital care of pediatric catatonia patients and compares treatments for neurotypical patients and those with NDDs. Methods: Retrospective cohort study from 1/1/2018 to 6/1/2023 of two academic medical centers of patients aged 18 and younger with catatonia. Patients were retrospectively assessed using the clinical global impressions-improvement (CGI-I) by two independent reviewers. Results: One hundred sixty-five patients were hospitalized for catatonia, of whom 50.3% had an NDD. Median age was 15. One hundred sixty-four patients were treated with a benzodiazepine, with a median maximum 24-hour dose of 6 mg lorazepam-equivalents, which did not differ for patients with and without NDDs. Electroconvulsive therapy (ECT) was utilized in 14.5% of patients. Median length of medical hospitalization was 5 days and hospitalizations were longer in neurotypical patients than in patients with NDDs. In an ordinal regression model, the probability of observing at least "much improvement" (CGI < 3) was 88.3% (95% CI: 82.4% to 92.3%), with NDD diagnosis associated with a lower odds of clinical response. Conclusions: The probability of patients achieving a CGI-I score indicating at least "much improvement" was 88.3%. Administered benzodiazepine dose and ECT treatment were similar for all patients, but neurotypical patients had longer hospitalizations than those with NDDs and had a higher odds of a more favorable clinical response. Research under controlled conditions is needed to optimize and endure equitable catatonia treatment in youth.

Generalized Periodic Discharges Associated With Catatonia and Delirium: A Case Series.

OBJECTIVE: Generalized periodic discharges are a repeated and generalized electroencephalography (EEG) pattern that can be seen in the context of altered mental status. This article describes a series of five individuals with generalized periodic discharges who demonstrated signs and symptoms of catatonia, a treatable neuropsychiatric condition. METHODS: Inpatients with a clinical diagnosis of catatonia, determined with the Bush-Francis Catatonia Rating Scale (BFCRS), and EEG recordings with generalized periodic discharges were analyzed in a retrospective case series. RESULTS: Five patients with catatonia and generalized periodic discharges on EEG were evaluated from among 106 patients with catatonia and contemporaneous EEG measurements. Four of these patients showed an improvement in catatonia severity when treated with benzodiazepines, with an average reduction of 6.75 points on the BFCRS. CONCLUSIONS: Among patients with generalized periodic discharges, catatonia should be considered, in the appropriate clinical context. Patients with generalized periodic discharges and catatonia may benefit from treatment with empiric trials of benzodiazepines.

Diagnostic features of paediatric catatonia: multisite retrospective cohort study.

BACKGROUND: Catatonia is a neuropsychiatric disorder characterised by psychomotor changes that can affect individuals across the lifespan. Although features of catatonia have been described in adults, the most common clinical symptoms among paediatric patients with catatonia are not well characterised. AIMS: The goal of this study was to characterise the symptoms of catatonia demonstrated by paediatric patients, and to explore demographic and diagnostic factors associated with greater catatonia severity. METHOD: We conducted a multicentre retrospective cohort study, from 1 January 2018 to 6 January 2023, of patients aged 18 and younger with a clinical diagnosis of catatonia and symptom assessment using the Bush Francis Catatonia Rating Scale (BFCRS). RESULTS: A total of 143 patients met inclusion criteria. The median age was 15 (interquartile range: 13-16) years and 66 (46.2%) patients were female. Neurodevelopmental disabilities were present in 55 (38.5%) patients. Patients demonstrated a mean of 6.0 ± 2.1 signs of catatonia on the Bush Francis Catatonia Screening Item, with a mean BFCRS score of 15.0 ± 5.9. Among the 23 items of the BFCRS, six were present in >50% of patients (staring, mutism, immobility/stupor, withdrawal, posturing/catalepsy, rigidity), and four were present in <20% of cases (waxy flexibility, mitgehen, gegenhalten, grasp reflex). In an adjusted model, patients with neurodevelopmental disorders demonstrated greater BFCRS severity than those with other diagnoses. CONCLUSIONS: Catatonia was diagnosed in a range of mental health conditions. Further research is needed to define optimal diagnostic criteria for catatonia in paediatric patients, and clarify the clinical course of the disorder.

Stress-induced failure of embodied cognition: A general model.

We derive the classic, ubiquitous, but enigmatic Yerkes-Dodson effect of applied stress on real-world performance in a highly natural manner from fundamental assumptions on cognition and its dynamics, as constrained by the asymptotic limit theorems of information and control theories. We greatly extend the basic approach by showing how differences in an underlying probability model can affect the dynamics of decision across a broad range of cognitive enterprise. Most particularly, however, this development may help inform our understanding of the different expressions of human psychopathology. A 'thin tailed' underlying distribution appears to characterize expression of 'ordinary' situational depression/anxiety symptoms of conditions like burnout induced by toxic stress. A 'fat tailed' underlying distribution appears to be associated with brain structure and function abnormalities leading to serious mental illness and poor decision making where symptoms are not only emerging in the setting of severe stress but may also appear in a highly punctuated manner at relatively lower levels of stress. A simple hierarchical optimization shows how environmental 'shadow price' constraints can buffer or aggravate the effects of stress and arousal. Extension of the underlying theory to other patterns of pathology, like immune disorders and premature aging, seems apt. Applications to the punctuated dynamics of institutional cognition under stress also appear possible. Ultimately, the probability models studied here can be converted to new statistical tools for the analysis of observational and experimental data.

Brain evolution and the meaning of catatonia - An update.

Back in 2004, in a chapter titled "Brain Evolution and the Meaning of Catatonia", a case was made that the syndrome's core meaning is embedded in millions of years of vertebrate brain evolution. (Fricchione, 2004) In this update, advances over the last almost 20 years, in catatonia theory and research in particular, and pertinent neuropsychiatry in general, will be applied to this question of meaning. The approach will rely heavily on a number of thought leaders, including Nicos Tinbergen, Paul MacLean, John Bowlby, M. Marsel Mesulam, Bruce McEwen and Karl Friston. Their guidance will be supplemented with a selected survey of 21sty century neuropsychiatry, neurophysiology, molecular biology, neuroimaging and neurotherapeutics as applied to the catatonic syndrome. In an attempt to address the question of the meaning of the catatonic syndrome in human life, we will employ two conceptual networks representing the intersubjectivity of the quantitative conceptual network of physical terms and the subjectivity of the qualitative conceptual network of mental and spiritual terms. In the process, a common referent providing extensional identity may emerge (Goodman, 1991). The goal of this exercise is to enhance our attunement with the experience of patients suffering with catatonia. A deeper understanding of catatonia's origins in brain evolution and of the challenges of individual epigenetic development in the setting of environmental events coupled with appreciation of what has been described as the most painful mammalian condition, that of separation, has the potential to foster greater efforts on the part of clinicians to diagnose and treat patients who present with catatonia. In addition, in this ancient and extreme tactic, evolved to provide safety from extreme survival threat, one can speculate what is at the core of human fear and the challenge it presents to all of us. And when the biology, psychology and sociology of catatonia are examined, the nature of solutions to the challenge may emerge.

Lorazepam in catatonia - Past, present and future of a clinical success story.

The effect of lorazepam in the treatment of catatonia is outstanding and almost immediate. Clinicians are familiar with its effects: mute patients can speak again, akinetic patients can move again and patients with negativism can eat and drink again within usually a short duration of about 10 min to 1-2 h. Fear is often gone after lorazepam administration. While not always effective, the introduction of lorazepam into clinical practice represented a breakthrough and was often life-saving for many patients suffering from catatonia. It is rare to observe such rapid therapeutic effects in other domains of psychiatry. In this narrative review we will briefly look at the past, present and future of lorazepam in the treatment of catatonia. It is gratifying to reflect on the fact that clinicians using the age-old medical practice of observation and empirical treatment succeeded in advancing the management of catatonia 40 years ago. The present evidence shows that the clinical effect of lorazepam in catatonia treatment is excellent and more or less immediate although it remains to be explicitly tested against other substances such as diazepam, zolpidem, clozapine, quetiapine, amantadine, memantine, valproate and dantrolene in randomized clinical trials. In addition, future studies need to answer the question how long lorazepam should be given to patients with catatonia, months or even years? This narrative review promotes the rapid use of lorazepam in the treatment of acute catatonic patients and stipulates further scientific examination of its often impressive clinical effects.

Molecular and immunological origins of catatonia.

Catatonia occurs secondary to both primary psychiatric and neuromedical etiologies. Emerging evidence suggests possible linkages between causes of catatonia and neuroinflammation. These include obvious infectious and inflammatory etiologies, common neuromedical illnesses such as delirium, and psychiatric entities such as depression and autism-spectrum disorders. Symptoms of sickness behavior, thought to be a downstream effect of the cytokine response, are common in many of these etiologies and overlap significantly with symptoms of catatonia. Furthermore, there are syndromes that overlap with catatonia that some would consider variants, including neuroleptic malignant syndrome (NMS) and akinetic mutism, which may also have neuroinflammatory underpinnings. Low serum iron, a common finding in NMS and malignant catatonia, may be caused by the acute phase response. Cellular hits involving either pathogen-associated molecular patterns (PAMP) danger signals or the damage-associated molecular patterns (DAMP) danger signals of severe psychosocial stress may set the stage for a common pathway immunoactivation state that could lower the threshold for a catatonic state in susceptible individuals. Immunoactivation leading to dysfunction in the anterior cingulate cortex (ACC)/mid-cingulate cortex (MCC)/medial prefrontal cortex (mPFC)/paralimbic cortico-striato-thalamo-cortical (CSTC) circuit, involved in motivation and movement, may be particularly important in generating the motor and behavioral symptoms of catatonia.

The predictive validity of a Brain Care Score for dementia and stroke: data from the UK Biobank cohort.

Introduction: The 21-point Brain Care Score (BCS) was developed through a modified Delphi process in partnership with practitioners and patients to promote behavior changes and lifestyle choices in order to sustainably reduce the risk of dementia and stroke. We aimed to assess the associations of the BCS with risk of incident dementia and stroke. Methods: The BCS was derived from the United Kingdom Biobank (UKB) baseline evaluation for participants aged 40-69 years, recruited between 2006-2010. Associations of BCS and risk of subsequent incident dementia and stroke were estimated using Cox proportional hazard regressions, adjusted for sex assigned at birth and stratified by age groups at baseline. Results: The BCS (median: 12; IQR:11-14) was derived for 398,990 UKB participants (mean age: 57; females: 54%). There were 5,354 incident cases of dementia and 7,259 incident cases of stroke recorded during a median follow-up of 12.5 years. A five-point higher BCS at baseline was associated with a 59% (95%CI: 40-72%) lower risk of dementia among participants aged <50. Among those aged 50-59, the figure was 32% (95%CI: 20-42%) and 8% (95%CI: 2-14%) for those aged >59 years. A five-point higher BCS was associated with a 48% (95%CI: 39-56%) lower risk of stroke among participants aged <50, 52% (95%CI, 47-56%) among those aged 50-59, and 33% (95%CI, 29-37%) among those aged >59. Discussion: The BCS has clinically relevant and statistically significant associations with risk of dementia and stroke in approximately 0.4 million UK people. Future research includes investigating the feasibility, adaptability and implementation of the BCS for patients and providers worldwide.

Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.

The British Association for Psychopharmacology developed an evidence-based consensus guideline on the management of catatonia. A group of international experts from a wide range of disciplines was assembled. Evidence was gathered from existing systematic reviews and the primary literature. Recommendations were made on the basis of this evidence and were graded in terms of their strength. The guideline initially covers the diagnosis, aetiology, clinical features and descriptive epidemiology of catatonia. Clinical assessments, including history, physical examination and investigations are then considered. Treatment with benzodiazepines, electroconvulsive therapy and other pharmacological and neuromodulatory therapies is covered. Special regard is given to periodic catatonia, malignant catatonia, neuroleptic malignant syndrome and antipsychotic-induced catatonia. There is attention to the needs of particular groups, namely children and adolescents, older adults, women in the perinatal period, people with autism spectrum disorder and those with certain medical conditions. Clinical trials were uncommon, and the recommendations in this guideline are mainly informed by small observational studies, case series and case reports, which highlights the need for randomised controlled trials and prospective cohort studies in this area.

A retrospective data analysis of psychiatric cases in Hargeisa, Somaliland between 2019 and 2020.

Background: In Somaliland, an estimated one person in every two households suffers from psychiatric disorders. Despite this, access to mental health care is limited because of shortages in facilities, human resources, funding and stigma. Aim: To present the proportion of psychiatric disorders encountered in outpatient psychiatry clinics. Setting: The University if Hargeisa (UoH), Hargesisa, Somaliland. Methods: De-identified data on patients accessing psychiatric care from doctor trainees in the dual psychiatry-neurology residency program at UoH from January 2019 to June 2020 were included in the analysis. The Institutional Review Board from UoH approved data collection and analysis. The most common psychiatric diagnoses were summarised overall and by sex and age. Results: A total of 752 patients were included in the analysis. Most were male (54.7%), with an average age of 34.9 years. The most common psychiatric diagnoses were schizophrenia (28.0%), major depressive disorder (MDD) (14.3%) and bipolar disorder type 1 (BD1) (10.5%). When stratified by sex, patients with schizophrenia and BD1 were more likely to be male (73.5% and 53.3%, respectively), and those with MDD were more likely to be female (58.8%). Trauma- and stressor-related disorders accounted for 0.4% of cases, while 0.8% of patients presented with substance use disorders (alcohol and khat), which is an underestimate of the widespread use in Somaliland. Conclusion: Additional research using structured clinical interviews is needed to determine the epidemiology of psychiatric disorders and promote policies aiming to decrease neuropsychiatric mortality and morbidity. Contribution: This work presents the first data collection related to neuropsychiatric disorders in Somaliland.

A Link Between Inflammatory Mechanisms and Fibromyalgia.

Fibromyalgia (FM) is a condition characterized by chronic widespread pain, which has traditionally been considered psychogenic in nature due to lack of known underlying organic pathophysiology. In more recent years, inflammation of the nervous system has become increasingly recognized as a sign of neuropsychiatric conditions, and this association may enhance our knowledge of conditions such as FM. Emerging evidence has suggested inflammation, particularly neuroinflammation, as a potential contributor underlying the etiology of FM. Studies have searched for linked biomarkers with mixed results, though the literature is beginning to point to increased systemic levels of pro-inflammatory cytokines such as IL-6 and IL-8 in patients with FM relative to healthy controls. A multicenter imaging study has also reported results suggestive of microglial activation related to the presence of FM. Given the consistency in neuroinflammatory effects implicated in "sickness behavior" characteristic of chronic systemic inflammatory conditions such as cancer or rheumatic diseases, therein springs the hypothesis for a connection between FM and neuroinflammation as discussed in this chapter.