Cognitive correlates of abnormal myelination in psychosis

Vanes, Lucy; Mouchlianitis, Elias; Barry, Elizabeth; Patel, Krisna; Wong, Katie; Shergill, Sukhwinder S.

doi:10.1038/s41598-019-41679-z

Cited by 16 publications

(10 citation statements)

References 61 publications

(62 reference statements)

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“…Furthermore, psychotic symptoms are related to functional connectivity alterations in the frontostriatal, frontotemporal, and frontoparietal circuits[ 132 ]. The frontostriatal circuit comprises the connections between the PFC and basal ganglia[ 128 ].…”

Section: Evidence Of Wm Alterations In Schizophrenia and Bipolar Diso...mentioning

confidence: 99%

“…Patients with schizophrenia have compromised fornix integrity and disrupted functional connectivity between the PFC and the hippocampus[ 138 , 139 ]. Further analysis of functional connectivity has provided evidence of alterations in the frontostriatal and frontoparietal circuits that are also related to cognitive dysfunctions in schizophrenia subjects[ 132 ].…”

Section: Evidence Of Wm Alterations In Schizophrenia and Bipolar Diso...mentioning

confidence: 99%

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Insights into myelin dysfunction in schizophrenia and bipolar disorder

Valdés-Tovar¹,

Rodríguez-Ramírez²,

Rodríguez-Cárdenas³

et al. 2022

WJP

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Schizophrenia and bipolar disorder are disabling psychiatric disorders with a worldwide prevalence of approximately 1%. Both disorders present chronic and deteriorating prognoses that impose a large burden, not only on patients but also on society and health systems. These mental illnesses share several clinical and neurobiological traits; of these traits, oligodendroglial dysfunction and alterations to white matter (WM) tracts could underlie the disconnection between brain regions related to their symptomatic domains. WM is mainly composed of heavily myelinated axons and glial cells. Myelin internodes are discrete axon-wrapping membrane sheaths formed by oligodendrocyte processes. Myelin ensheathment allows fast and efficient conduction of nerve impulses through the nodes of Ranvier, improving the overall function of neuronal circuits. Rapid and precisely synchronized nerve impulse conduction through fibers that connect distant brain structures is crucial for higher-level functions, such as cognition, memory, mood, and language. Several cellular and subcellular anomalies related to myelin and oligodendrocytes have been found in postmortem samples from patients with schizophrenia or bipolar disorder, and neuroimaging techniques have revealed consistent alterations at the macroscale connectomic level in both disorders. In this work, evidence regarding these multilevel alterations in oligodendrocytes and myelinated tracts is discussed, and the involvement of proteins in key functions of the oligodendroglial lineage, such as oligodendrogenesis and myelination, is highlighted. The molecular components of the axo-myelin unit could be important targets for novel therapeutic approaches to schizophrenia and bipolar disorder.

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Section: Evidence Of Wm Alterations In Schizophrenia and Bipolar Diso...mentioning

confidence: 99%

Section: Evidence Of Wm Alterations In Schizophrenia and Bipolar Diso...mentioning

confidence: 99%

Insights into myelin dysfunction in schizophrenia and bipolar disorder

Valdés-Tovar¹,

Rodríguez-Ramírez²,

Rodríguez-Cárdenas³

et al. 2022

WJP

View full text Add to dashboard Cite

show abstract

“…Myelin underpins the efficiency and speed of neuronal signal conduction, enabling rapid communication between disparate brain regions and efficient functional integration during cognitive processing. White matter changes linked to myelin are associated with cognitive function both in health (Lu et al, ; Mabbott, Noseworthy, Bouffet, Laughlin, & Rockel, ; Nagy, Westerberg, & Klingberg, ) and pathology (Vanes et al, ; Vanes, Mouchlianitis, Wood, & Shergill, ). Individual differences in white matter myelination may thus be a general risk factor for or an outcome of psychiatric disorders (Fields, ).…”

Section: Introductionmentioning

confidence: 99%

White matter tract myelin maturation and its association with general psychopathology in adolescence and early adulthood

Vanes

Moutoussis

Ziegler

et al. 2019

Human Brain Mapping

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Adolescence is a time period associated with marked brain maturation that coincides with an enhanced risk for onset of psychiatric disorder. White matter tract myelination, a process that continues to unfold throughout adolescence, is reported to be abnormal in several psychiatric disorders. Here, we ask whether psychiatric vulnerability is linked to aberrant developmental myelination trajectories. We assessed a marker of myelin maturation, using magnetisation transfer (MT) imaging, in 10 major white matter tracts. We then investigated its relationship to the expression of a general psychopathology "p-factor" in a longitudinal analysis of 293 healthy participants between the ages of 14 and 24. We observed significant longitudinal MT increase across the full age spectrum in anterior thalamic radiation, hippocampal cingulum, dorsal cingulum and superior longitudinal fasciculus. MT increase in the inferior fronto-occipital fasciculus, inferior longitudinal fasciculus and uncinate fasciculus was pronounced in younger participants but levelled off during the transition into young adulthood. Crucially, longitudinal MT increase in dorsal cingulum and uncinate fasciculus decelerated as a function of mean p-factor scores over the study period. This suggests that an increased expression of psychopathology is closely linked to lower rates of myelin maturation in selective brain tracts over time. Impaired myelin growth in limbic association fibres may serve as a neural marker for emerging mental illness during the course of adolescence and early adulthood. K E Y W O R D S cingulum, general psychopathology, myelin, structural connectivity, uncinate fasciculus

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“…This is consistent with the present data where changes in the paw angle of the forelimb and hindlimb in the scrambled treated stroke group were also associated with a reduced volume of myelinated tracts in the ischemic hemisphere. White matter pathways are critical for cognitive functions (Fields, 2008 ; Chevalier et al, 2015 ; Vanes et al, 2019 ). Studies have suggested myelin breakdown occurs as a consequence of stroke and due to chronological aging (Guttmann et al, 1998 ; Peters et al, 2000 ; Bartzokis et al, 2001 ).…”

Section: Discussionmentioning

confidence: 99%

Mir363-3p Treatment Attenuates Long-Term Cognitive Deficits Precipitated by an Ischemic Stroke in Middle-Aged Female Rats

Panta

Montgomery

Nicolas

et al. 2020

Front. Aging Neurosci.

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Cognitive impairment and memory loss are commonly seen after stroke and a third of patients will develop signs of dementia a year after stroke. Despite a large number of studies on the beneficial effects of neuroprotectants, few studies have examined the effects of these compounds/interventions on long-term cognitive impairment. Our previous work showed that the microRNA mir363-3p reduced infarct volume and sensory-motor impairment in the acute stage of stroke in middle-aged females but not males. Thus, the present study determined the impact of mir363-3p treatment on stroke-induced cognitive impairment in middle-aged females. Sprague–Dawley female rats (12 months of age) were subjected to middle cerebral artery occlusion (MCAo; or sham surgery) and injected (iv) with mir363-3p mimic (MCAo + mir363-3p) or scrambled oligos (MCAo + scrambled) 4 h later. Sensory-motor performance was assessed in the acute phase (2–5 days after stroke), while all other behaviors were tested 6 months after MCAo (18 months of age). Cognitive function was assessed by the novel object recognition test (declarative memory) and the Barnes maze (spatial memory). The MCAo + scrambled group showed reduced preference for a novel object after the stroke and poor learning in the spatial memory task. In contrast, mir363-3p treated animals were similar to either their baseline performance or to the sham group. Histological analysis showed significant deterioration of specific white matter tracts due to stroke, which was attenuated in mir363-3p treated animals. The present data builds on our previous finding to show that a neuroprotectant can abrogate the long-term effects of stroke.

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Cognitive correlates of abnormal myelination in psychosis

Cited by 16 publications

References 61 publications

Insights into myelin dysfunction in schizophrenia and bipolar disorder

Insights into myelin dysfunction in schizophrenia and bipolar disorder

White matter tract myelin maturation and its association with general psychopathology in adolescence and early adulthood

Mir363-3p Treatment Attenuates Long-Term Cognitive Deficits Precipitated by an Ischemic Stroke in Middle-Aged Female Rats

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