Mapping cortical surface features in treatment resistant schizophrenia with in vivo structural MRI

Barry, Elizabeth; Vanes, Lucy; Andrews, Derek Sayre; Patel, Krisna; Horne, Charlotte Mary; Mouchlianitis, Elias; Hellyer, Peter J.; Shergill, Sukhi

doi:10.1016/j.psychres.2019.02.028

Cited by 21 publications

(31 citation statements)

References 82 publications

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“…This is in line with the current findings of TR linked to the genetics of schizophrenia (Owen et al, 2016). Furthermore, the current association between TR and PRS-SZ might indicate underlying factors in TR, as recent studies have revealed genetic pleiotropy between schizophrenia and phenotypes such as brain structure volumes (Terwisscha van Scheltinga et al, 2013;Smeland et al, 2018;Chen et al, 2019), immune related conditions (Andreassen et al, 2015) body mass index (Bahrami et al 2020) and lipids (Andreassen et al, 2013), all of which potentially related to antipsychotic drug treatment response (Barry et al, 2019;Hutcheson et al, 2014;Noto et al, 2015;Pillinger et al, 2020).…”

Section: Discussionsupporting

confidence: 85%

Indicated association between polygenic risk score and treatment-resistance in a naturalistic sample of patients with schizophrenia spectrum disorders

Werner

Wirgenes

Haram

et al. 2020

Schizophrenia Research

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Background: One third of people diagnosed with schizophrenia fail to respond adequately to antipsychotic medication, resulting in persisting disabling symptoms, higher rates of hospitalisation and higher costs for society. In an effort to better understand the mechanisms behind resistance to antipsychotic treatment in schizophrenia, we investigated its potential relationship to the genetic architecture of the disorder.Methods: Patients diagnosed with a schizophrenia spectrum disorder (N=321) were classified as either being treatment-resistant (N=108) or non-treatment-resistant (N=213) to antipsychotic medication using defined consensus criteria. A schizophrenia polygenic risk score based on genome-wide association studies (GWAS) was calculated for each patient and binary logistic regression was performed to investigate the association between polygenetic risk and treatment resistance. We adjusted for principal components, batch number, age and sex. Additional analyses were performed to investigate associations with demographic and clinical variables.Results: High levels of polygenic risk score for schizophrenia significantly predicted treatment resistance (p=0.003). The positive predictive value of the model was 61.5% and the negative predictive value was 71.7%. The association was significant for one (p=0.01) out of five tested SNP significance thresholds. Season of birth was able to predict treatmentresistance in the regression model (p=0.05). Conclusions:The study indicates that treatment-resistance to antipsychotic medication is associated with higher polygenetic risk of schizophrenia, suggesting a link between antipsychotics mechanism of action and the genetic underpinnings of the disorder.

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Section: Discussionsupporting

confidence: 85%

Indicated association between polygenic risk score and treatment-resistance in a naturalistic sample of patients with schizophrenia spectrum disorders

Werner

Wirgenes

Haram

et al. 2020

Schizophrenia Research

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“…A recent study comparing 145 APD-naive first-episode psychosis (FEP) patients and 147 controls found that CT decrease as an effect of age was more pronounced in patients, 15 while another showed CT reductions were greater in treatment resistant patients with SZ than nonresistant SZ. 16 As a measure, gyrification index is of particular interest due to its potential as a marker of abnormal neurodevelopment. 17,18 Altered gyrification patterns have been reported across different illness stages [19][20][21][22] and among first-degree relatives.…”

Section: Introductionmentioning

confidence: 99%

A Prospective Longitudinal Investigation of Cortical Thickness and Gyrification in Schizophrenia

et al. 2020

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Background: Cortical thickness (CT) and gyrification are complementary indices that assess different aspects of gray matter structural integrity. Both neurodevelopment insults and acute tissue response to antipsychotic medication could underlie the known heterogeneity of treatment response and are well-suited for interrogation into the relationship between gray matter morphometry and clinical outcomes in schizophrenia (SZ). Methods: Using a prospective design, we enrolled 34 unmedicated patients with SZ and 23 healthy controls. Patients were scanned at baseline and after a 6-week trial with risperidone. CT and local gyrification index (LGI) values were quantified from structural MRI scans using FreeSurfer 5.3. Results: We found reduced CT and LGI in patients compared to controls. Vertex-wise analyses demonstrated that hypogyrification was most prominent in the inferior frontal cortex, temporal cortex, insula, pre/postcentral gyri, temporoparietal junction, and the supramarginal gyrus. Baseline CT was predictive of subsequent response to antipsychotic treatment, and increase in CT after 6 weeks was correlated with greater symptom reductions. Conclusions: In summary, we report evidence of reduced CT and LGI in unmedicated patients compared to controls, suggesting involvement of different aspects of gray matter morphometry in the pathophysiology of SZ. Importantly, we found that lower CT at baseline and greater increase of CT following 6 weeks of treatment with risperidone were associated with better clinical response. Our results suggest that cortical thinning may normalize as a result of a good response to antipsychotic medication, possibly by alleviating potential neurotoxic processes underlying gray matter deterioration.

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“…Abnormal myelination in SZ has been mainly reported in white matter (WM) based on the diffusion tensor imaging (DTI) technique (Gangadin, Nasib, Sommer, & Mandl, ; Hamoda et al, ). Structural imaging of the gray matter (GM) has identified morphological changes such as reduced volume, thickness and surface area in SZ (Barry et al, ; Gao et al, ; Storvestre et al, ). Some studies suggest that in SZ, changes of myelination in WM might explain the morphometric change in GM since neural fibers mostly start from or end in the GM (Sasamoto et al, ).…”

Section: Introductionmentioning

confidence: 99%

Depth‐dependent abnormal cortical myelination in first‐episode treatment‐naïve schizophrenia

Wei

Zhang

et al. 2020

Human Brain Mapping

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Myelination is key to effective message passing in the central nervous system and is likely linked to the pathogenesis of schizophrenia (SZ). Emerging evidence indicates that a large portion of intracortical myelin insulates inhibitory interneurons that are highly relevant to pathogenesis of schizophrenia. Here for the first time, we characterized intracortical myelination across the entire cortical surface in first‐episode treatment‐naïve patients with schizophrenia (FES) using T1w/T2w ratio of structural MRI, FES patients exhibited significantly higher myelin content in the left inferior parietal lobe, supramarginal gyrus, and superior temporal gyrus in the superficial layer, as well as left IPL in the middle layer, but significantly lower myelin content in the left middle insula and posterior cingulate gyrus. Years of education, a proxy for onset of functional decline, significantly altered the relationship between abnormal parietal and posterior cingulate myelination and clinical symptoms, indicating that the pathoplastic role of myelination hinges on the age of onset of functional decline. In addition, higher myelination generally related to better cognitive function in younger subjects but worse cognitive function in older subjects. We conclude that FES is characterized by increased myelination of the superficial layers of the parietal–temporal association cortex, but reduced myelination of the cingulo‐insular midcortical layer cortex. Intracortical myelin content affects both cognitive functioning and symptom burden in FES, with the effect conditional upon age and timing of onset of functional decline. These results suggest myelination might be a critical biological target for procognitive interventions in SZ.

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Mapping cortical surface features in treatment resistant schizophrenia with in vivo structural MRI

Cited by 21 publications

References 82 publications

Indicated association between polygenic risk score and treatment-resistance in a naturalistic sample of patients with schizophrenia spectrum disorders

Indicated association between polygenic risk score and treatment-resistance in a naturalistic sample of patients with schizophrenia spectrum disorders

A Prospective Longitudinal Investigation of Cortical Thickness and Gyrification in Schizophrenia

Depth‐dependent abnormal cortical myelination in first‐episode treatment‐naïve schizophrenia

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