In vivo imaging of neuroinflammation in schizophrenia

Pasternak, Ofer; Kubicki, Marek; Shenton, Martha E.

doi:10.1016/j.schres.2015.05.034

Cited by 132 publications

(124 citation statements)

References 171 publications

(227 reference statements)

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“…Interest in FWI is motivated by the hypothesis that neuroinflammation plays a role in the etiology of schizophrenia (133) and that such inflammation might damage oligodendrocytes and thereby impact myelin (134, 135). FWI is sensitive to increases in extracellular water, as might be caused by edema (136, 137), and widespread changes in this measure have been shown in FE schizophrenia (138). A chronic population showed results more consistent with degeneration than active inflammation (139), which may imply that there are fundamentally different neural changes at different stages of the disorder.…”

Section: Open Questions and Future Directionsmentioning

confidence: 99%

Diffusion Imaging of White Matter in Schizophrenia: Progress and Future Directions

Karlsgodt

2016

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

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Diffusion tensor imaging (DTI) is a powerful tool for the in-vivo assessment of white matter microstructure. The application of DTI methodologies to the study of schizophrenia has supported and advanced the hypothesis of schizophrenia as a disorder of disrupted connectivity. In the context of impaired structural connectivity, the extended time frame of white matter development may offer unique opportunities for treatment that can capitalize on the neural flexibility that is still present in the period leading up to and after disease onset. Therefore, it is important to gain a clear understanding of white matter deficits and how they may emerge and change across the illness. However, while there is broad consistency in the findings of white matter deficits in patients with schizophrenia, there is also a great deal of variability in specific findings across studies. In this review, the aim is to move beyond summarizing case-control analyses, to consider the many factors that may impact DTI measures, to explain variability of findings, and to explore future directions for the field. The topics explored include ways to parse DTI patterns associated with different disease subtypes, ways in which novel and established treatments might interact with or enhance white matter, ways of dissociating developmental change from the disease process itself, and understanding the role of emerging analytic methodologies.

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Section: Open Questions and Future Directionsmentioning

confidence: 99%

Diffusion Imaging of White Matter in Schizophrenia: Progress and Future Directions

Karlsgodt

2016

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

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“…Even though the underlying mechanisms and functional role of increased hippocampal IL--1β expression remains to be examined in our model, our data clearly demonstrate that abnormal pro--inflammatory cytokine expression in the brain can occur without concomitant microglia abnormalities. These findings may also have important implications for the current attempts to define "neuroinflammation" in neurodevelopmental disorders such as schizophrenia and autism, especially for those that rely on the examination of microglia only (Doorduin et al, 2009;Kenk et al, 2015;Morgan et al, 2010;Pasternak et al, 2015;Tetreault et al, 2012;van Berckel et al, 2008).…”

mentioning

confidence: 98%

Prenatal immune activation causes hippocampal synaptic deficits in the absence of overt microglia anomalies

Giovanoli

Weber‐Stadlbauer

Schedlowski

et al. 2016

Brain, Behavior, and Immunity

126

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Prenatal exposure to infectious or inflammatory insults can increase the risk of developing neuropsychiatric disorder in later life, including schizophrenia, bipolar disorder, and autism. These brain disorders are also characterized by pre-and postsynaptic deficits. Using a well-established mouse model of maternal exposure to the viral mimetic polyriboinosinic-polyribocytidilic acid [poly(I:C)], we examined whether prenatal immune activation might cause synaptic deficits in the hippocampal formation of pubescent and adult offspring. Based on the widely appreciated role of microglia in synaptic pruning, we further explored possible associations between synaptic deficits and microglia anomalies in offspring of poly(I:C)-exposed and control mothers. We found that prenatal immune activation induced an adult onset of presynaptic hippocampal deficits (as evaluated by synaptophysin and bassoon density). The early-life insult further caused postsynaptic hippocampal deficits in pubescence (as evaluated by PSD95 and SynGAP density), some of which persisted into adulthood. In contrast, prenatal immune activation did not change microglia (or astrocyte) density, nor did it alter their activation phenotypes. The prenatal manipulation did also not cause signs of persistent systemic inflammation. Despite the absence of overt glial anomalies or systemic inflammation, adult offspring exposed to prenatal immune activation displayed increased hippocampal IL-1 levels. Taken together, our findings demonstrate that age-dependent synaptic deficits and abnormal pro-inflammatory cytokine expression can occur during postnatal brain maturation in the absence of microglial anomalies or systemic inflammation. AbstractPrenatal exposure to infectious or inflammatory insults can increase the risk of developing neuropsychiatric disorder in later life, including schizophrenia, bipolar disorder, and autism. These brain disorders are also characterized by pre--and postsynaptic deficits.Using a well--established mouse model of maternal exposure to the viral mimetic polyriboinosinic--polyribocytidilic acid [poly(I:C)], we examined whether prenatal immune activation might cause synaptic deficits in the hippocampal formation of pubescent and adult offspring. Based on the widely appreciated role of microglia in synaptic pruning, we further explored possible associations between synaptic deficits and microglia anomalies in offspring of poly(I:C)--exposed and control mothers. We found that prenatal immune activation induced adult onset of presynaptic hippocampal deficits (as evaluated by synaptophysin and bassoon density). The early--life insult further caused postsynaptic hippocampal deficits in pubescence (as evaluated by PSD95 and SynGAP density), some of which persisted into adulthood. In contrast, prenatal immune activation did not change microglia (or astrocyte) density, nor did it alter their activation phenotypes. The prenatal manipulation did also not cause signs of persistent systemic inflammation. Despite the absence of overt glial a...

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“…MD changes can reflect e.g., alteration of cellularity, or necrosis (Alexander et al., 2011; Concha, 2014), but MD also increases in vasogenic edema, which could be indicative of e.g., neuroinflammation (Pasternak et al., 2015) that is suspected to occur in CRPS. However, more research is needed to study the role of central inflammaltion in CRPS and its relationship to DTI abnormalities.…”

Section: Discussionmentioning

confidence: 99%

“…However, more research is needed to study the role of central inflammaltion in CRPS and its relationship to DTI abnormalities. For example, neuroinflammation‐specific changes of extracellular volume are more likely to be identified with free‐water imaging which is sensitive to water diffusion in the extracellular space (Pasternak et al., 2012, 2015). …”

Section: Discussionmentioning

confidence: 99%

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Complex regional pain syndrome: The matter of white matter?

et al. 2017

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IntroductionMany central pathophysiological aspects of complex regional pain syndrome (CRPS) are still unknown. Although brain‐imaging studies are increasingly supporting the contribution of the central nervous system to the generation and maintenance of the CRPS pain, the brain's white‐matter alterations are seldom investigated.MethodsIn this study, we used diffusion tensor imaging to explore white‐matter changes in twelve CRPS‐type‐1 female patients suffering from chronic right upper‐limb pain compared with twelve healthy control subjects.ResultsTract‐based spatial‐statistics analysis revealed significantly higher mean diffusivity, axial diffusivity, and radial diffusivity in the CRPS patients, suggesting that the structural connectivity is altered in CRPS. All these measures were altered in the genu, body, and splenium of corpus callosum, as well as in the left anterior and posterior and the right superior parts of the corona radiata. Axial diffusivity was significantly correlated with clinical motor symptoms at whole‐brain level, supporting the physiological significance of the observed white‐matter abnormalities.ConclusionsAltogether, our findings further corroborate the involvement of the central nervous system in CRPS.

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In vivo imaging of neuroinflammation in schizophrenia

Cited by 132 publications

References 171 publications

Diffusion Imaging of White Matter in Schizophrenia: Progress and Future Directions

Diffusion Imaging of White Matter in Schizophrenia: Progress and Future Directions

Prenatal immune activation causes hippocampal synaptic deficits in the absence of overt microglia anomalies

Complex regional pain syndrome: The matter of white matter?

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