Microstructural White Matter and Links With Subcortical Structures in Chronic Schizophrenia: A Free-Water Imaging Approach

Gurholt, Tiril P.; Haukvik, Unn K.; Lonning, Vera; Jönsson, Erik G.; Pasternak, Ofer; Agartz, Ingrid

doi:10.3389/fpsyt.2020.00056

Cited by 9 publications

(11 citation statements)

References 55 publications

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“…Besides the high Cohen's d effect size estimate, we found no significant association of regional FA with either current or cumulative antipsychotic exposure. These null-findings in line with previous studies in EOP patients [12,[18][19][20][21] and studies in adult-onset psychosis [5,22]. For instance, studying white matter microstructure in 1,963 patients with schizophrenia, Kelly and colleagues found no significant effect of medication PLOS ONE dosage [5].…”

Section: Discussionsupporting

confidence: 78%

“…As the consistency of DWI metrics seems affected by brain edema and inflammatory response, future studies can benefit from using tools such as free water imaging. Free-water imaging separates the contribution of extracellular water from the diffusion measure, leading to a higher specificity in detecting microstructural changes [22].…”

Section: Discussionmentioning

confidence: 99%

“…The absence of an antipsychotic dosage effect in EOP patients could reflect small sample sizes and young patients with shorter medication histories. However, large-scale cohort studies in adult-onset schizophrenia also do not find an effect of medication dosage on white-matter microstructure [5,22]. Hence, medication dosage might not be a driving factor for potential effects of antipsychotic medication on the brain.…”

Section: Introductionmentioning

confidence: 99%

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Exploring white matter microstructure and the impact of antipsychotics in adolescent-onset psychosis

et al. 2020

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White matter abnormalities are well-established in adult patients with psychosis. Less is known about abnormalities in the rarely occurring adolescent early onset psychosis (EOP). In particular, whether antipsychotic medication might impact white matter microstructure is not known. Using 3T diffusion weighted imaging, we investigated differences in white matter microstructure and the impact of antipsychotic medication status in medicated (n = 11) and unmedicated (n = 11) EOP patients relative to healthy controls (n = 33), aged between 12-18 years. Using Tract-based Spatial Statistics, we calculate case-control differences in scalar diffusion measures, i.e. fractional anisotropy (FA), axial diffusion (AD) and radial diffusion (RD), and investigated their association with antipsychotic medication in patients. We found significantly lower FA in the left genu of the corpus callosum, the left anterior corona radiata (ACR) and the right superior longitudinal fasciculus in EOP patients relative to healthy controls. AD values were also lower in the left ACR, largely overlapping with the FA findings. Mean FA in the left ACR was significantly associated with antipsychotic medication status (Cohen's d = 1.37, 95% CI [0.01, 2.68], p = 0.008), showing higher FA values in medicated compared to unmedicated EOP patients. The present study is the first to link antipsychotic medication status to altered regional FA in the left ACR, a region hypothesized to contribute to the etiology of psychosis. Replications are warranted to draw firm conclusions about putatively enhancing effects of antipsychotic medication on white matter microstructure in adolescent-onset psychosis.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Exploring white matter microstructure and the impact of antipsychotics in adolescent-onset psychosis

et al. 2020

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“…Although there were insufficient data to investigate the association between FW values and PANSS subscales, one study [ 25 ] reported a secondary analysis revealing patients with positive symptoms (olfactory hallucinations, thought disorder, pressured speech, and inappropriate affect) had significantly higher FW values relative to patients who were asymptomatic. One other study [ 32 ] also showed that total Scale for the Assessment of Positive Symptoms scores were significantly associated with increased FW values in the right posterior thalamic radiatia and the left sagittal stratum.…”

Section: Resultsmentioning

confidence: 91%

White-matter free-water diffusion MRI in schizophrenia: a systematic review and meta-analysis

Figueiredo

Borgan

Pasternak

et al. 2022

Neuropsychopharmacol.

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White-matter abnormalities, including increases in extracellular free-water, are implicated in the pathophysiology of schizophrenia. Recent advances in diffusion magnetic resonance imaging (MRI) enable free-water levels to be indexed. However, the brain levels in patients with schizophrenia have not yet been systematically investigated. We aimed to meta-analyse white-matter free-water levels in patients with schizophrenia compared to healthy volunteers. We performed a literature search in EMBASE, MEDLINE, and PsycINFO databases. Diffusion MRI studies reporting free-water in patients with schizophrenia compared to healthy controls were included. We investigated the effect of demographic variables, illness duration, chlorpromazine equivalents of antipsychotic medication, type of scanner, and clinical symptoms severity on free-water measures. Ten studies, including five of first episode of psychosis have investigated free-water levels in schizophrenia, with significantly higher levels reported in whole-brain and specific brain regions (including corona radiata, internal capsule, superior and inferior longitudinal fasciculus, cingulum bundle, and corpus callosum). Six studies, including a total of 614 participants met the inclusion criteria for quantitative analysis. Whole-brain free-water levels were significantly higher in patients relative to healthy volunteers (Hedge’s g = 0.38, 95% confidence interval (CI) 0.07–0.69, p = 0.02). Sex moderated this effect, such that smaller effects were seen in samples with more females (z = −2.54, p < 0.05), but antipsychotic dose, illness duration and symptom severity did not. Patients with schizophrenia have increased free-water compared to healthy volunteers. Future studies are necessary to determine the pathological sources of increased free-water, and its relationship with illness duration and severity.

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“…On the one hand, some studies indicated that WM integrity may be affected by the type of medication or illness duration (Ozcelik-Eroglu et al, 2014;Samartzis et al, 2014). On the other hand, the recent studies on big-sample sizes revealed that the dose of medication (calculated as the chlorpromazine equivalent) did not affect the diffusivity parameters of WM (Kelly et al, 2018;Koshiyama, 2020;Joo et al, 2020;Gurholt et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

On the relation of white matter brain abnormalities and the asociality symptoms in schizophrenia outpatients – a DTI study

Adamczyk¹,

Płonka²,

Kruk³

et al. 2021

Acta Neurobiologiae Experimentalis

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Recent MRI studies have shown that abnormal functional connections in schizophrenia coexist with subtle changes in the structure of axons in the brain. However, there is a discrepancy in the literature concerning the relationship between white matter abnormalities and the occurrence of negative psychopathological symptoms. In the present study, we investigate the relationship between the altered white matter structure and specific psychopathology symptoms, i.e., subscales of Positive and Negative Syndrome Scale (PANSS) and Brief Negative Symptoms Scale (BNSS) in a sample of schizophrenia outpatients. For investigation on white matter abnormalities in schizophrenia, the diffusion tensor imaging analysis of between-group differences in main diffusion parameters by tract-based spatial statistics was conducted on schizophrenia outpatients and healthy controls. Hence, the correlation of PANSS and BNSS psychopathology subscales in the clinical group with fractional anisotropy was analyzed in the 17 selected cortical regions of interest. Presented between-group results revealed widespread loss of white matter integrity located across the brain in schizophrenia outpatients. Results on the white matter relationship with psychopathology revealed the negative correlation between fractional anisotropy in the left orbital prefrontal cortex, right Heschl's gyrus, bilateral precuneus and posterior cingulate cortex and the severity of asociality, as assessed with the BNSS. In conclusion, the presented study confirms the previous evidence on the widespread white matter abnormalities in schizophrenia outpatients and indicates the existence of the subtle but specific association between fractional anisotropy in the fronto-temporo-parietal regions with the asociality.

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Microstructural White Matter and Links With Subcortical Structures in Chronic Schizophrenia: A Free-Water Imaging Approach

Abstract: system in patients with chronic schizophrenia and schizoaffective disorder. Findings warrant replication in larger samples.

Cited by 9 publications

References 55 publications

Exploring white matter microstructure and the impact of antipsychotics in adolescent-onset psychosis

Exploring white matter microstructure and the impact of antipsychotics in adolescent-onset psychosis

White-matter free-water diffusion MRI in schizophrenia: a systematic review and meta-analysis

On the relation of white matter brain abnormalities and the asociality symptoms in schizophrenia outpatients – a DTI study

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