Functional brain networks in the schizophrenia spectrum and bipolar disorder with psychosis

Psychotic experiences have been proposed to lie on a spectrum, ranging from subclinical experiences to treatment-resistant schizophrenia. We aimed to characterize functional connectivity and brain network characteristics in relation to the schizophrenia spectrum and bipolar disorder with psychosis to disentangle neural correlates to psychosis. Additionally, we studied antipsychotic medication and lithium effects on network characteristics. We analyzed functional connectivity strength and network topology in 487 resting-state functional MRI scans of individuals with schizophrenia spectrum disorder (SCZ), bipolar disorder with a history of psychotic experiences (BD), treatment-naïve subclinical psychosis (SCP), and healthy controls (HC). Since differences in connectivity strength may confound group comparisons of brain network topology, we analyzed characteristics of the minimum spanning tree (MST), a relatively unbiased backbone of the network. SCZ and SCP subjects had a lower connectivity strength than BD and HC individuals but showed no differences in network topology. In contrast, BD patients showed a less integrated network topology but no disturbances in connectivity strength. No differences in outcome measures were found between SCP and SCZ, or between BD patients that used antipsychotic medication or lithium and those that did not. We conclude that functional networks in patients prone to psychosis have different signatures for chronic SCZ patients and SCP compared to euthymic BD patients, with a limited role for medication. Connectivity strength effects may have confounded previous studies, as no functional network alterations were found in SCZ after strict correction for connectivity strength.</p

The association between frailty and MRI features of cerebral small vessel disease.

Frailty is a common syndrome in older individuals that is associated with poor cognitive outcome. The underlying brain correlates of frailty are unclear. The aim of this study was to investigate the association between frailty and MRI features of cerebral small vessel disease in a group of non-demented older individuals. We included 170 participants who were classified as frail (n = 30), pre-frail (n = 85) or non-frail (n = 55). The association of frailty and white matter hyperintensity volume and shape features, lacunar infarcts and cerebral perfusion was investigated by regression analyses adjusted for age and sex. Frail and pre-frail participants were older, more often female and showed higher white matter hyperintensity volume (0.69 [95%-CI 0.08 to 1.31], p = 0.03 respectively 0.43 [95%-CI: 0.04 to 0.82], p = 0.03) compared to non-frail participants. Frail participants showed a non-significant trend, and pre-frail participants showed a more complex shape of white matter hyperintensities (concavity index: 0.04 [95%-CI: 0.03 to 0.08], p = 0.03; fractal dimensions: 0.07 [95%-CI: 0.00 to 0.15], p = 0.05) compared to non-frail participants. No between group differences were found in gray matter perfusion or in the presence of lacunar infarcts. In conclusion, increased white matter hyperintensity volume and a more complex white matter hyperintensity shape may be structural brain correlates of the frailty phenotype

The association between frailty and MRI features of cerebral small vessel disease

Abstract: Frailty is a common syndrome in older individuals that is associated with poor cognitive outcome. The underlying brain correlates of frailty are unclear. The aim of this study was to investigate the association between frailty and MRI features of cerebral small vessel disease in a group of non-demented older individuals. We included 170 participants who were classified as frail (n = 30), pre-frail (n = 85) or non-frail (n = 55). The association of frailty and white matter hyperintensity volume and shape features, lacunar infarcts and cerebral perfusion was investigated by regression analyses adjusted for age and sex. Frail and pre-frail participants were older, more often female and showed higher white matter hyperintensity volume (0.69 [95%-CI 0.08 to 1.31], p = 0.03 respectively 0.43 [95%-CI: 0.04 to 0.82], p = 0.03) compared to non-frail participants. Frail participants showed a non-significant trend, and pre-frail participants showed a more complex shape of white matter hyperintensities (concavity index: 0.04 [95%-CI: 0.03 to 0.08], p = 0.03; fractal dimensions: 0.07 [95%-CI: 0.00 to 0.15], p = 0.05) compared to non-frail participants. No between group differences were found in gray matter perfusion or in the presence of lacunar infarcts. In conclusion, increased white matter hyperintensity volume and a more complex white matter hyperintensity shape may be structural brain correlates of the frailty phenotype

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

Delirium as a disorder of brain network disintegration

Delirium is a common neuropsychiatric syndrome, characterized by acute change in attention and awareness, as direct consequence of an underlying medical condition. It is affecting 10-50% of the hospitalized elderly. Delirium is a burden for patients and related to negative outcomes, such as long-term cognitive impairment. The development of delirium is usually the result of an interaction of various heterogeneous risk factors. Predisposing risk factors, such as older age or cognitive impairment, cover the baseline vulnerability to delirium. Precipitating risk factors for delirium, such as sedation, determine acute changes that can trigger the syndrome. The underlying mechanism of how (combinations of) these risk factors lead to delirium is unknown. In addition, although several hypothesis exist, the pathophysiology of the clinical syndrome is generally unknown. Nevertheless, previous studies have indicated that the acute state of delirium can be accompanied with alterations in brain (network) activity. Studying the brain network in relation to delirium may therefore give us new insights in this complex clinical syndrome. The aim of this dissertation was to evaluate the hypothesis of delirium as a disorder of brain network disintegration. The hypothesis was tested in three different aspects. Brain network disintegration was evaluated as biological substrate of (1) vulnerability for delirium, (2) the clinical syndrome of delirium and (3) longitudinal changes after delirium. Taken together, this dissertation may add the following conclusions to the existing literature: 1. Predisposing risk for delirium does not appear to be associated with similar functional network alterations as observed during delirium. 2. Network disintegration can be defined as biological characteristic for the clinical syndrome of delirium. Alterations in functional network efficiency and integration seem to be related to the clinical symptoms of delirium and may recover when delirium resolves. 3. Delirium is associated with a decrease in global connectivity strength of the functional brain network over time. This alteration could be the biological substrate of impaired outcomes of delirium, such as longterm cognitive dysfunction or dementia. The theory of delirium as a disorder of brain network disintegration does not have to replace other hypotheses on the pathophysiology of delirium. Previous hypotheses indicated neuroinflammation, neurotransmitter disturbances, neuronal aging, oxidative stress or neuroendocrine disturbances as an essential underlying biological mechanism for delirium. It remains to be studied to what extent brain network alterations are associated with these other hypotheses. Presumably, integrating different hypotheses for delirium may be beneficial in elucidating the complex pathophysiology

Delirium as a disorder of brain network disintegration

Delirium is a common neuropsychiatric syndrome, characterized by acute change in attention and awareness, as direct consequence of an underlying medical condition. It is affecting 10-50% of the hospitalized elderly. Delirium is a burden for patients and related to negative outcomes, such as long-term cognitive impairment. The development of delirium is usually the result of an interaction of various heterogeneous risk factors. Predisposing risk factors, such as older age or cognitive impairment, cover the baseline vulnerability to delirium. Precipitating risk factors for delirium, such as sedation, determine acute changes that can trigger the syndrome. The underlying mechanism of how (combinations of) these risk factors lead to delirium is unknown. In addition, although several hypothesis exist, the pathophysiology of the clinical syndrome is generally unknown. Nevertheless, previous studies have indicated that the acute state of delirium can be accompanied with alterations in brain (network) activity. Studying the brain network in relation to delirium may therefore give us new insights in this complex clinical syndrome. The aim of this dissertation was to evaluate the hypothesis of delirium as a disorder of brain network disintegration. The hypothesis was tested in three different aspects. Brain network disintegration was evaluated as biological substrate of (1) vulnerability for delirium, (2) the clinical syndrome of delirium and (3) longitudinal changes after delirium. Taken together, this dissertation may add the following conclusions to the existing literature: 1. Predisposing risk for delirium does not appear to be associated with similar functional network alterations as observed during delirium. 2. Network disintegration can be defined as biological characteristic for the clinical syndrome of delirium. Alterations in functional network efficiency and integration seem to be related to the clinical symptoms of delirium and may recover when delirium resolves. 3. Delirium is associated with a decrease in global connectivity strength of the functional brain network over time. This alteration could be the biological substrate of impaired outcomes of delirium, such as longterm cognitive dysfunction or dementia. The theory of delirium as a disorder of brain network disintegration does not have to replace other hypotheses on the pathophysiology of delirium. Previous hypotheses indicated neuroinflammation, neurotransmitter disturbances, neuronal aging, oxidative stress or neuroendocrine disturbances as an essential underlying biological mechanism for delirium. It remains to be studied to what extent brain network alterations are associated with these other hypotheses. Presumably, integrating different hypotheses for delirium may be beneficial in elucidating the complex pathophysiology

Youths growing up in the French banlieues: Partners that make the city

How can cities become ‘livable’ for all urban residents? In this chapter, the authors explore the livable city as a city that is livable also for youths and also in marginalized urban areas by zooming in on the case of French youths growing up in the banlieues of Paris. Drawing on ethnographic research in Seine-Saint-Denis, a banlieue northeast of Paris, the authors explore the activities which banlieue youths undertake to realize quality of life in their city. The findings show that youths in the banlieues engage in ‘making their city’ in everyday practices and informal partnerships, even if they do not engage in ‘governing their city’ through formalized partnerships. Based on this study, the authors suggest that attention for informal practices that shape collective life in the city could inform a more inclusive perspective on urban decision making. Exploring the activities that youths take to ‘make the city’, this chapter teaches the reader not only that youths can be vital actors in partnerships for livable cities, but even more so how these partnerships can be effective and legitimate from the perspective of marginalized urban youths

Effects of omega-3 polyunsaturated fatty acids on human brain morphology and function : What is the evidence?

Public opinion and media coverage suggest that there are benefits of long-chain ω-3 polyunsaturated fatty acid (LC-PUFA) intake on brain functioning. However, it is an open question whether this is indeed the case. Therefore, we reviewed the evidence for effects of ω-3 LC-PUFA on human brain morphology and function. We included studies on (1) naturalistic long-term ω-3 LC-PUFA intake during life (2) the effects of short-term ω-3 LC-PUFA supplementation in healthy subjects and (3) the effects of ω-3 LC-PUFA supplementation as alternative or add-on treatment for psychiatric or neurological disorders. To date, 24 studies have been published on the effect of ω-3 LC-PUFA on brain function and structure. Findings from naturalistic studies and clinical trials in healthy individuals indicate that ω-3 LC-PUFA intake may be associated with increased functional activation of the prefrontal cortex in children, and greater gray matter volume and white matter integrity during aging. However, most naturalistic studies were cross-sectional or did not find any effect on cognition. As such, it is hard to estimate the magnitude of any beneficial effects. Furthermore, there is only limited evidence to support that ω-3 LC-PUFA supplementation is beneficial in brain disorders, such as Alzheimer's Disease, Attention Deficit/Hyperactivity Disorder, Major Depressive Disorder and schizophrenia. Overall, the literature suggests that sensitivity to supplementation may vary over development, and as a consequence of brain disorders. The biological mechanisms underlying any (beneficial) effects ω-3 LC-PUFAs on the brain are currently unknown and need to be investigated

MRI Markers of Neurodegenerative and Neurovascular Changes in Relation to Postoperative Delirium and Postoperative Cognitive Decline

Postoperative delirium (POD) and postoperative cognitive decline (POCD) are common in elderly patients. The aim of the present review was to explore the association of neurodegenerative and neurovascular changes with the occurrence of POD and POCD. Fifteen MRI studies were identified by combining multiple search terms for POD, POCD, and brain imaging. These studies described a total of 1,422 patients and were all observational in design. Neurodegenerative changes (global and regional brain volumes) did not show a consistent association with the occurrence of POD (four studies) or POCD (two studies). In contrast, neurovascular changes (white matter hyperintensities and cerebral infarcts) were more consistently associated with the occurrence of POD (seven studies) and POCD (five studies). In conclusion, neurovascular changes appear to be consistently associated with the occurrence of POD and POCD, and may identify patients at increased risk of these conditions. Larger prospective studies are needed to study the consistency of these findings and to unravel the underlying pathophysiological mechanisms