White matter alterations in individuals experiencing attenuated positive psychotic symptoms

Objective: To analyse the available data regarding the presentation of psychosis in diseases of central nervous system (CNS) white matter. Method: The available neurological and psychiatric literature on developmental, neoplastic, infective, immunological and other white matter diseases was reviewed. Results: A number of diseases of the white matter can present as schizophrenia-like psychoses, including leukodystrophies, neoplasms, velocardiofacial syndrome, callosal anomalies and inflammatory diseases. Conclusions: Production of psychotic symptoms may result from functional asynchrony of interdependent regions, due to alterations in critical circuits as a result of pathology. The nature, location and timing of white matter pathology seem to be the key factors in the development of psychosis, especially during the critical adolescent period of association area myelination. Diseases that disrupt the normal formation of myelin appear to cause psychosis at higher rates than those that disrupt mature myelinated structures. Diffuse rather than discrete lesions, in particular those affecting frontotemporal zones, are also more strongly associated with schizophrenia-like psychosis. These illnesses point to the central role that white matter plays in maintaining CNS connectivity and to how pathology of the white matter may contribute to the neurobiology of psychosis.

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Multiple sclerosis⋮ the disease and its manifestations

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.1999.0506 ◽

1999 ◽

Vol 354 (1390) ◽

pp. 1615-1622 ◽

Cited By ~ 39

Author(s):

W. I. McDonald ◽

M. A. Ron

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Neurological Deficit ◽

Demyelinating Disease ◽

Psychotic Symptoms ◽

Cerebral White Matter ◽

Supporting Evidence ◽

Specific Test ◽

Cognitive Disturbances ◽

Magnetic Resonance Imaging Mri

Multiple sclerosis is an immune–mediated inflammatory demyelinating disease of the central nervous system clinically characterized by relapses and remissions of neurological disturbance. A typical relapse, exemplified by optic neuritis, increases in severity over a week or two and after approximately one month begins to remit. Resolution takes place over the course of two to three months. In the early stages, clinical recovery is virtually complete, though persistent abnormalities of conduction can usually be detected by evoked potential techniques and persistent structural abnormalities can be detected by magnetic resonance imaging (MRI). These techniques, together with cerebrospinal fluid examination for oligoclonal IgG, provide supporting evidence for the diagnosis which, in the absence of a specific test, nevertheless remains primarily clinical. The course of the disease is very variable, but after a number of years neurological deficit begins to accumulate after each relapse. In most patients, the relapsing and remitting phase of the disease is followed by a phase of continuous progression of disability. Cognitive disturbances can be detected in many patients even quite early in the course of the illness. Deficits in attention, memory and executive skills may be prominent and tend to become increasingly prominent as neurological deficit increases, although this is not always the case. There is some correlation between the extent of MRI abnormalities in the cerebral white matter and the severity of cognitive deficit. Depression and anxiety are commonly experienced but are poorly correlated to the lesion load seen on MRI. In contrast, the much rarer psychotic symptoms, euphoria and emotional lability are closely linked to the severity of white matter disease.

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Association between white matter fiber integrity and subclinical psychotic symptoms in schizophrenia patients and unaffected relatives

Schizophrenia Research ◽

10.1016/j.schres.2012.06.001 ◽

2012 ◽

Vol 140 (1-3) ◽

pp. 129-135 ◽

Cited By ~ 45

Author(s):

Christian Knöchel ◽

Laurence O'Dwyer ◽

Gilberto Alves ◽

Britta Reinke ◽

Jörg Magerkurth ◽

...

Keyword(s):

White Matter ◽

Psychotic Symptoms ◽

Subclinical Psychotic Symptoms

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Poster #M59 THE “FIBRE” PATH TO PSYCHOSIS? CAN ADVANCED DIFFUSION IMAGING CAPTURE WHITE MATTER BRAIN ANOMALIES IN ADOLESCENTS EXPERIENCING PSYCHOTIC SYMPTOMS?

Schizophrenia Research ◽

10.1016/s0920-9964(14)70609-7 ◽

2014 ◽

Vol 153 ◽

pp. S210

Author(s):

Erik O'Hanlon ◽

Alexander Leemans ◽

Mary C. Clarke ◽

Ian Kelleher ◽

Francesco Amico ◽

...

Keyword(s):

White Matter ◽

Diffusion Imaging ◽

Psychotic Symptoms ◽

Brain Anomalies

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State-dependent microstructural white matter changes in drug-naïve patients with first-episode psychosis

Psychological Medicine ◽

10.1017/s0033291717001015 ◽

2017 ◽

Vol 47 (15) ◽

pp. 2613-2627 ◽

Cited By ~ 14

Author(s):

M. H. Serpa ◽

J. Doshi ◽

G. Erus ◽

T. M. Chaim-Avancini ◽

M. Cavallet ◽

...

Keyword(s):

White Matter ◽

Diffusion Tensor ◽

Clinical Status ◽

First Episode Psychosis ◽

Rate Of Change ◽

Psychotic Symptoms ◽

First Episode ◽

Sustained Remission ◽

Episode Psychosis ◽

Over Time

BackgroundDiffusion tensor imaging (DTI) studies have consistently shown white matter (WM) microstructural abnormalities in schizophrenia. Whether or not such alterations could vary depending on clinical status (i.e. acute psychosis v. remission) remains to be investigated.MethodsTwenty-five treatment-naïve first-episode psychosis (FEP) patients and 51 healthy-controls (HC) underwent MRI scanning at baseline. Twenty-one patients were re-scanned as soon as they achieved sustained remission of symptoms; 36 HC were also scanned twice. Rate-of-change maps of longitudinal DTI changes were calculated for in order to examine WM alterations associated with changes in clinical status. We conducted voxelwise analyses of fractional anisotropy (FA) and trace (TR) maps.ResultsAt baseline, FEP presented reductions of FA in comparison with HC [p < 0.05, false-discovery rate (FDR)-corrected] affecting fronto-limbic WM and associative, projective and commissural fasciculi. After symptom remission, patients showed FA increase over time (p < 0.001, uncorrected) in some of the above WM tracts, namely the right anterior thalamic radiation, right uncinate fasciculus/inferior fronto-occipital fasciculus, and left inferior fronto-occipital fasciculus/inferior longitudinal fasciculus. We also found significant correlations between reductions in PANSS scores and FA increases over time (p < 0.05, FDR-corrected).ConclusionsWM changes affecting brain tracts critical to the integration of perceptual information, cognition and emotions are detectable soon after the onset of FEP and may partially reverse in direct relation to the remission of acute psychotic symptoms. Our findings reinforce the view that WM abnormalities in brain tracts are a key neurobiological feature of acute psychotic disorders, and recovery from such WM pathology can lead to amelioration of symptoms.

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Grey and white matter associations of psychotic-like experiences in a general population sample (UK Biobank)

Translational Psychiatry ◽

10.1038/s41398-020-01131-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Julie Schoorl ◽

Miruna C. Barbu ◽

Xueyi Shen ◽

Mat R. Harris ◽

Mark J. Adams ◽

...

Keyword(s):

White Matter ◽

General Population ◽

Psychotic Disorders ◽

Population Sample ◽

Brain Structures ◽

Depressive Illness ◽

Psychotic Symptoms ◽

Intracranial Volume ◽

Uk Biobank ◽

White Matter Microstructure

AbstractThere has been a substantial amount of research reporting the neuroanatomical associations of psychotic symptoms in people with schizophrenia. Comparatively little attention has been paid to the neuroimaging correlates of subclinical psychotic symptoms, so-called “psychotic-like experiences” (PLEs), within large healthy populations. PLEs are relatively common in the general population (7–13%), can be distressing and negatively affect health. This study therefore examined gray and white matter associations of four different PLEs (auditory or visual PLEs, and delusional ideas about conspiracies or communications) in subjects of the UK Biobank study with neuroimaging data (N = 21,390, mean age = 63 years). We tested for associations between any PLE (N = 768) and individual PLEs with gray and white matter brain structures, controlling for sex, age, intracranial volume, scanning site, and position in the scanner. Individuals that reported having experienced auditory hallucinations (N = 272) were found to have smaller volumes of the caudate, putamen, and accumbens (β = −0.115–0.134, pcorrected = 0.048–0.036), and reduced temporal lobe volume (β = −0.017, pcorrected = 0.047) compared to those that did not. People who indicated that they had ever believed in unreal conspiracies (N = 111) had a larger volume of the left amygdala (β = 0.023, pcorrected = 0.038). Individuals that reported a history of visual PLEs (N = 435) were found to have reduced white matter microstructure of the forceps major (β = −0.029, pcorrected = 0.009), an effect that was more marked in participants who reported PLEs as distressing. These associations were not accounted for by diagnoses of psychotic or depressive illness, nor the known risk factors for psychotic symptoms of childhood adversity or cannabis use. These findings suggest altered regional gray matter volumes and white matter microstructure in association with PLEs in the general population. They further suggest that these alterations may appear more frequently with the presentation of different psychotic symptoms in the absence of clinically diagnosed psychotic disorders.

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M162. FRONTO-STRIATAL-THALAMIC CIRCUITRY ABNORMALITIES IN WHITE MATTER TRACTS IN INDIVIDUALS WITH 22Q11.2 DELETION SYNDROME

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa030.474 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S197-S198

Author(s):

Carina Heller ◽

Saskia Steinmann ◽

Nikos Makris ◽

Lily Charron ◽

Kevin M Antshel ◽

...

Keyword(s):

Young Adults ◽

White Matter ◽

Cognitive Decline ◽

22Q11.2 Deletion Syndrome ◽

Deletion Syndrome ◽

Psychotic Symptoms ◽

Healthy Controls ◽

22Q11.2 Deletion ◽

Prodromal Symptoms ◽

The Right

Abstract Background Cognitive decline is considered a fundamental component in schizophrenia. Abnormalities in fronto-striatal-thalamic (FST) sub-circuits are present in schizophrenia and are associated with cognitive impairments. However, it remains unknown whether abnormalities in FST sub-circuits are present before psychosis onset. This may be elucidated by investigating young adults with 22q11.2 deletion syndrome (22q11DS), of whom 30% will develop schizophrenia in adulthood. In 22q11DS, cognitive decline, most pronounced in Verbal IQ (VIQ), precedes the onset of psychosis and those who develop psychosis diverge more strongly from a typical cognitive trajectory. Based on these findings, studies of young adults with 22q11DS without overt psychosis but with prodromal symptoms may increase our understanding of cognitive manifestations and early pathology in FST sub-circuits in schizophrenia. Here we examined white matter (WM) tracts in FST sub-circuits, especially those involving dorsolateral (DLPFC) and ventrolateral prefrontal cortex (VLPFC), and their associations with VIQ in young adults with 22q11DS with and without prodromal symptoms. Methods We compared Fractional Anisotropy (FA), Axial Diffusivity (AD), and Radial Diffusivity (RD) in tracts of the FST sub-circuits in 21 individuals with 22q11DS with prodromal symptoms (age: M=21.43) and 30 individuals without prodromal symptoms (age: M=20.73) to 30 healthy controls (age: M=20.89). Two-tensor tractography was applied to reconstruct WM fiber tracts of the whole brain, followed by applying the White Matter Query Language (WMQL) method to select tracts between striatum and thalamus, with the rostral middle frontal gyrus (rMFG) and inferior frontal gyrus (IFG), representing DLPFC and VLPFC. This yielded four tracts of interest: thalamus-rMFG, thalamus-IFG, striatum-rMFG, and striatum-IFG tracts. Additionally, correlations between the dMRI measures and scores on VIQ were performed. Results FA was significantly increased, while RD was significantly decreased in most WM tracts in both 22q11DS groups when compared to healthy controls. In the whole 22q11DS group, VIQ correlated negatively with FA in the right thalamus-IFG tract (r=-0.336, p=.018), while RD correlated positively with VIQ in the right thalamus-IFG tract (r=0.290, p=.043) in individuals with 22q11DS, such that increased FA and decreased RD were associated with a lower VIQ. We followed up on the results in individuals with 22q11DS with prodromal symptoms to determine whether the presence of prodromal symptoms drove the correlations. VIQ correlated significantly with FA (r=-0.491, p=0.024, FDR-adjusted=0.048) and significantly at trend level with RD (r=0.487, p=0.025, FDR-adjusted=0.050) in the right thalamus-IFG tract in individuals with 22q11DS with prodromal symptoms. Discussion Microstructural abnormalities in brain WM tracts connecting the thalamus and the striatum with prefrontal cortices are present in young adults with 22q11DS with and without prodromal symptoms compared to healthy controls. These abnormalities are associated with the individuals’ cognitive performance in VIQ in individuals with 22q11DS with prodromal symptoms and therefore emphasize the potential involvement of the FST sub-circuits in schizophrenia. While changes in FST circuitry have been reported in patients with schizophrenia, we observed that changes in FST circuitry are also present in young adults with 22q11DS at risk for but without psychotic symptoms. Our results suggest that psychosis onset in 22q11DS may be associated with a complex pattern of WM alterations. Furthermore, cognitive abnormalities, especially in VIQ, present an important preclinical risk factor for psychosis in 22q11DS.

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Abnormalities in brain white matter in adolescents with 22q11.2 deletion syndrome and psychotic symptoms

Brain Imaging and Behavior ◽

10.1007/s11682-016-9602-x ◽

2016 ◽

Vol 11 (5) ◽

pp. 1353-1364 ◽

Cited By ~ 11

Author(s):

Zora Kikinis ◽

Kang Ik K. Cho ◽

Ioana L. Coman ◽

Petya D. Radoeva ◽

Sylvain Bouix ◽

...

Keyword(s):

White Matter ◽

22Q11.2 Deletion Syndrome ◽

Deletion Syndrome ◽

Psychotic Symptoms ◽

22Q11.2 Deletion ◽

Brain White Matter

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Cerebellar white-matter changes in cannabis users with and without schizophrenia

Psychological Medicine ◽

10.1017/s003329171100050x ◽

2011 ◽

Vol 41 (11) ◽

pp. 2349-2359 ◽

Cited By ~ 58

Author(s):

N. Solowij ◽

M. Yücel ◽

C. Respondek ◽

S. Whittle ◽

E. Lindsay ◽

...

Keyword(s):

White Matter ◽

Cannabinoid Receptors ◽

Cannabis Use ◽

Analysis Of Covariance ◽

Psychotic Symptoms ◽

White Matter Volume ◽

Cerebellar White Matter ◽

Matter Volume ◽

Mri Scans

BackgroundThe cerebellum is rich in cannabinoid receptors and implicated in the neuropathology of schizophrenia. Long-term cannabis use is associated with functional and structural brain changes similar to those evident in schizophrenia, yet its impact on cerebellar structure has not been determined. We examined cerebellar grey and white matter in cannabis users with and without schizophrenia.MethodSeventeen patients with schizophrenia and 31 healthy controls were recruited; 48% of the healthy group and 47% of the patients were long-term heavy cannabis users (mean 19.7 and 17.9 years near daily use respectively). Cerebellar measures were extracted from structural 3-T magnetic resonance imaging (MRI) scans using semi-automated methods, and examined using analysis of covariance (ANCOVA) and correlational analyses.ResultsCerebellar white-matter volume was reduced in cannabis users with and without schizophrenia compared to healthy non-users, by 29.7% and 23.9% respectively, and by 17.7% in patients without cannabis use. Healthy cannabis users did not differ in white-matter volume from either of the schizophrenia groups. There were no group differences in cerebellar grey matter or total volumes. Total cerebellar volume decreased as a function of duration of cannabis use in the healthy users. Psychotic symptoms and illness duration correlated with cerebellar measures differentially between patients with and without cannabis use.ConclusionsLong-term heavy cannabis use in healthy individuals is associated with smaller cerebellar white-matter volume similar to that observed in schizophrenia. Reduced volumes were even more pronounced in patients with schizophrenia who use cannabis. Cannabis use may alter the course of brain maturational processes associated with schizophrenia.

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