Thickness In Schizophrenia Research Articles

The Relationship of Cognitive Dysfunction with Inflammatory Markers and Carotid Intima Media Thickness in Schizophrenia.

Schizophrenia is a devastating and chronic mental disorder that affects 1% of the population worldwide. It is also associated with cognitive dysfunction and cardiovascular risk factors. The aim of this study is to investigate the relationship between cognitive impairment and some inflammatory markers and carotid intima-media thickness (CIMT) in schizophrenia. The participants of this study were 51 schizophrenia and 57 healthy controls (HC). The Positive and Negative Syndrome Scale (PANSS) was used for severity of illness, and the Montreal Cognitive Assessment Scale (MoCA) was used for cognitive functioning. The MoCA scores, some biochemical and inflammatory markers, and CIMT were compared between schizophrenia and HC groups. Of the patients with schizophrenia, 11 were women (21.6%), and 40 were men (78.4%). MoCA scores were lower, and levels of NLR, MLR, PLR, SII, CRP, ESR, and CIMT were higher in schizophrenia compared to the HC group (respectively; p < 0.001, p < 0.001, p = 0.035, p = 0.008, p = 0.002, p < 0.001, p < 0.001, p < 0.001). In the schizophrenia group, there was no correlation between MoCA and inflammatory markers. MoCA and CIMT had a significant negative and moderate correlation (p < 0.001). This is the first study to show the relationship between cognitive impairment and CIMT in schizophrenia. In this study, NLR, MLR, PLR, SII, CRP, and ESR markers were higher in schizophrenia compared to HC, indicating inflammation. Our finding of elevated CIMT in schizophrenia suggests that there may be an atherosclerotic process along with the inflammatory process. The finding of a positive correlation between cognitive impairment and CIMT may be promising for new therapies targeting the atherosclerotic process in the treatment of cognitive impairment.

Association between retinal vascular caliber and brain structure in schizophrenia.

Several lines of research in the last decade have indicated the potential utility of retina as a window to the brain. Emerging evidence suggests abnormalities in retinal vascular caliber in schizophrenia. However, the relationship between retinal vascular measures and brain structure has not been examined in schizophrenia to date. Hence, we examined the relationship between retinal vasculature measured using fundus photography and brain structure measured using magnetic resonance imaging. We recruited 17 healthy volunteers and 20 patients with schizophrenia. Using a non-mydriatic camera, we captured the images for left and right eyes separately and retinal vascular calibers were calculated using a semi-automated software package. Whole-brain anatomical T1 MPRAGE images were acquired using a 3-Tesla MRI scanner. Whole-brain and regional volume and cortical thickness were calculated using the Freesurfer software package. We used FreeSurfer's QDEC interface to compute vertex-by-vertex for analysis of the volume and cortical thickness. The relation between brain volume, cortical thickness, and retinal vascular caliber was examined using partial correlation and regression analysis. There was a significant negative correlation between average CRVE and global cortical mean thickness in schizophrenia but not in healthy. In schizophrenia patients, there was a significant negative correlation between average CRVE and cortical thickness in frontal regions - left rostral middle frontal, left superior frontal, and right caudal middle frontal gyri and posterior brain regions - left lateral occipital gyrus and left posterior cingulate cortex. The findings of the study suggest potential utility of retinal venular diameter as a proxy marker to abnormal neurodevelopment in schizophrenia.

Inter-Device Reliability of Swept Source and Spectral Domain Optical Coherence Tomography Retinal Structure Measurements in Schizophrenia

Optical coherence tomography (OCT) is used to study retinal structure in schizophrenia. Various generations of OCT are utilized in studies, which may introduce measurement variability. We investigated the inter- and intra-device agreement of macular thickness in schizophrenia, and macula and peripapillary group differences in schizophrenia using swept source OCT (SS-OCT).

Do Cognition and Psychopathology Vary With Cortical Structure? Neuroanatomical Subgroups Based on Cortical Thickness in Schizophrenia

Cortical thinning may index the neurobiological pathogenesis of schizophrenia. However, case-control studies ignore the neurobiological, symptomatic, and cognitive heterogeneity of the illness. To organize heterogeneity, unsupervised machine learning approaches can derive neuroanatomical subgroups with cortical thickness data and identify clinical and cognitive correlates.

Effects of neuroactive metabolites of the tryptophan pathway on working memory and cortical thickness in schizophrenia

A number of tryptophan metabolites known to be neuroactive have been examined for their potential associations with cognitive deficits in schizophrenia. Among these metabolites, kynurenic acid (KYNA), 5-hydroxyindole (5-HI), and quinolinic acid (QUIN) are documented in their diverse effects on α-7 nicotinic acetylcholine receptor (α7nAChR) and/or N-methyl-D-aspartate receptor (NMDAR), two of the receptor types thought to contribute to cognitive impairment in schizophrenia. In this study, serum levels of KYNA, 5-HI, and QUIN were measured in 195 patients with schizophrenia and in 70 healthy controls using liquid chromatography-tandem mass spectrometry; cognitive performance in MATRICS Consensus Cognitive Battery and cortical thickness measured by magnetic resonance imaging were obtained. Patients with schizophrenia had significantly lower serum KYNA (p < 0.001) and QUIN (p = 0.02) levels, and increased 5-HI/KYNA (p < 0.001) and QUIN/KYNA ratios (p < 0.001) compared with healthy controls. Multiple linear regression showed that working memory was positively correlated with serum 5-HI levels (t = 2.10, p = 0.04), but inversely correlated with KYNA concentrations (t = −2.01, p = 0.05) in patients. Patients with high 5-HI and low KYNA had better working memory than other subgroups (p = 0.01). Higher 5-HI levels were associated with thicker left lateral orbitofrontal cortex (t = 3.71, p = 2.94 × 10−4) in patients. The different effects of 5-HI and KYNA on working memory may appear consistent with their opposite receptor level mechanisms. Our findings appear to provide a new insight into the dynamic roles of tryptophan pathway metabolites on cognition, which may benefit novel therapeutic development that targets cognitive impairment in schizophrenia.

A surface-based morphometry study of risk and resilience markers associated with supramarginal thickness in schizophrenia

IntroductionConventional structural neuroimaging methods can identify changes in cortical thickness but cannot relate these changes to specific cortical layers due to a lack of sensitivity. However, several indirect measures sensitive to changes specifically occurring in supragranular cortical layers were developed recently (github.com/kwagstyl/schizophrenia_gyral_sulcal).ObjectivesThe aim was to assess the ability of these novel measures to detect cortical layers thickness characteristics potentially associated with risk or resilience to developing schizophrenia.Methods43 first-episode schizophrenia (FES) male patients, 29 non-converted individuals at ultra-high risk of psychosis (ncUHR, mean follow-up period – 6.5 years), and 43 matched healthy controls (HC) underwent structural MRI at 3T Philips scanner. Images were processed via FreeSurfer and MATLAB to derive two markers specific to supragranular thickness change: gyral-sulcal thickness differences (GSTD) and gyral-sulcal intrinsic curvature differences on pial surface (GSCD).ResultsGSCD measures were increased in temporal, parietal and occipital cortices, whereas both GSTD and GSCD were increased in the right frontal cortex in FES compared to HC. No GSTD or GSCD were changed in ncUHR compared to HC, and GSCD was decreased in the frontal cortex compared to FES.ConclusionsOur findings from the indirect measures indicate a potential predominance of supragranular thinning in FES and suggest that a supragranular thinning in the right frontal lobe might be associated with precipitating risk and/or illness effects of schizophrenia. At the same time, no clear supragranular markers directly associated with resilience or risk mechanisms were identified. The work was supported by RFBR grant 20-013-00748.

Retinal nerve fiber layer thickness changes in Schizophrenia: A meta-analysis of case–control studies

Studies using optical coherence tomography (OCT) to compare retinal nerve fiber layer thickness in subjects with schizophrenia and healthy controls have yielded inconsistent results. We aimed to compare changes in retinal nerve fiber layer thickness in schizophrenia and healthy controls via a meta-analysis. Relevant studies were selected via an electronic search of the Cochrane Controlled Trials Register, Pubmed, and Embase. All included studies measured average and 4-quadrant (temporal, superior, nasal, and inferior) retinal nerve fiber layer thickness via OCT. Statistical analysis was performed using RevMan 5.0 software. Seven case–control studies involving collective totals of 245 eyes in patients with schizophrenia and 220 eyes in healthy controls were ultimately included in this meta-analysis. Statistical analysis revealed that average retinal nerve fiber layer thickness in patients with schizophrenia was significantly reduced compared to that of healthy controls. Additionally, retinal nerve fiber layer thickness in the inferior quadrant, nasal quadrant, and temporal quadrant differed significantly between the two groups, while differences in the superior quadrant did not. In view of these results, we suggest that peripapillary retinal nerve fiber layer thickness as measured by OCT may be a useful tool for the diagnosis of schizophrenia.

C-Reactive Protein: Higher During Acute Psychotic Episodes and Related to Cortical Thickness in Schizophrenia and Healthy Controls.

There is increasing evidence for the role of inflammation in schizophrenia, yet the stability of increased peripheral inflammation in acute psychosis and the degree to which peripheral inflammation relates to cortical thickness, a measure of the degree of neuropathology, are unknown. In independent samples, we assessed the peripheral inflammation marker C-reactive protein (CRP) to determine the extent to which: (1) CRP was elevated and stable across admissions for acute psychosis, (2) cognition, daily function and symptom severity are characteristic of chronically ill patients with schizophrenia displaying elevated CRP, and (3) CRP levels predict cortical thickness. Study 1 assessed peripheral CRP (primary outcome) and other blood measures in 174/280 people with acute psychosis while Study 2 assessed peripheral CRP, cognition and cortical thickness (primary outcomes), symptoms, and daily function in 85/97 chronically ill patients with schizophrenia and 71/87 healthy controls. In acute psychosis, CRP and neutrophil-to-lymphocyte ratio were significantly elevated relative to a normal cutoff (with 59.8% of patients having elevated CRP) which remained elevated across admissions. CRP was significantly elevated in 43% of chronically ill patients with schizophrenia compared to 20% in controls. Elevated CRP patients displayed significantly worse working memory and CRP was inversely correlated with cortical thickness in frontal, insula, and temporal brain regions. This work supports the role of inflammation in psychotic illnesses and suggests that use of peripheral markers (e.g., CRP) in conjunction with diagnosis could be used to identify patients with more cortical neuropathology and cognitive deficits.

Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium

BackgroundThe profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group. MethodsThe study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11–78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10–87 years; 53% male) assessed with standardized methods at 39 centers worldwide. ResultsCompared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen’s d = −0.530/−0.516) and smaller surface area (left/right hemisphere: Cohen’s d = −0.251/−0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset. ConclusionsThe findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia.

Evaluation of retinal nerve fiber layer, macular, and choroidal thickness in schizophrenia: spectral optic coherence tomography findings

OBJECTIVES: The study was performed to evaluate the retinal nerve fiber layer (RNFL), macular, and subfoveal choroidal thickness (SFCT) in patients with schizophrenia and healthy controls using spe...

163. An Effect Size Profile of Cortical Thickness in Schizophrenia

163. An Effect Size Profile of Cortical Thickness in Schizophrenia

Decreases in retinal nerve fiber layer and ganglion cell-inner plexiform layer thickness in schizophrenia, relation to insight: a controlled study

Objective: The present study aimed to examine retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) thicknesses in schizophrenia patients according to the control group and in schizophrenia patients with good and poor insight. Methods: Sixty-three patients with schizophrenia recruited from the outpatient clinic of psychiatry and 39 healthy controls were included in the study. Patients were separated to two groups: good insight (n=31) and poor insight (n=32) schizophrenia. Group with schizophrenia were evaluated by using Positive and Negative Symptoms Scale (PANSS), Scale to Assess Unawareness of Mental Disorder. Changes in RNFL and GCIPL of all participants were analyzed with spectral optical coherence tomography (OCT). Results: Schizophrenia patients with good and poor insight were similar according to mean age of onset for illness, mean duration of illness, mean number of hospitalizations and mean daily used antipsychotic doses equivalent to chlorpromazine. There was no difference between the schizophrenia patients and the control group in terms of age and gender. In patients with schizophrenia all quadrants of RNFL, superior temporal (ST), superior (S), and inferior (I) quadrants of GCIPL were thinner than the controls. Inferior, inferior nasal quadrants of GCIPL and all quadrants of RNFL except nasal quadrant in schizophrenia patients with poor insight was found to be thinner than the schizophrenia patients with good insight and controls. Discussion: OCT can be used to detect neurodegeneration in schizophrenic patients. It can be argued that the GCIP layer may be a more sensitive biomarker than other retinal layers, requiring further investigation in this area.

Distinct Patterns of Cerebral Cortical Thinning in Schizophrenia: A Neuroimaging Data-Driven Approach.

Schizophrenia is an etiologically and clinically heterogeneous disorder. Although neuroimaging studies have revealed brain alterations in schizophrenia, most studies have assumed that the disorder is a single entity, neglecting the diversity of alterations observed in the disorder. The current study sought to explore the distinct patterns of altered cortical thickness in patients with schizophrenia and healthy individuals using a data-driven approach. Unsupervised clustering using self-organizing maps followed by a K-means algorithm was applied to regional cortical thickness data in 108 schizophrenia patients and 121 healthy controls. After clustering, the clinical characteristics and cortical thickness patterns of each cluster were assessed. Unsupervised clustering revealed that a 6-cluster solution was the most appropriate in this sample. There was substantial overlap between the patterns of cortical thickness in schizophrenia patients and healthy controls, although the distributions of the patients and controls differed across the clusters. The patterns of altered cortical thickness in schizophrenia exhibited cluster-specific features; patients within a cluster exhibited the most extensive cortical thinning, particularly in the medial prefrontal and temporal regions, while those in other clusters exhibited reduced cortical thickness in the medial frontal region or temporal lobe. Furthermore, in the schizophrenia group, extensive cortical thinning was correlated with a higher dosage of antipsychotic medication, while preserved cortical thickness appeared to be linked to less negative symptoms. This data-driven neuroimaging approach revealed distinct patterns of cortical thinning in schizophrenia, possibly reflecting the etiological heterogeneity of the disorder.

Allostatic load and reduced cortical thickness in schizophrenia

Structural imaging studies have consistently found reduced gray matter thickness of the cerebral cortex in schizophrenia, a finding that is evident in first episode psychosis and may be progressive in some cases. Although genetic predisposition and medication effects may contribute to cortical thinning, we hypothesize that the cumulative effects of stress may represent an environmental factor impacting brain morphology in schizophrenia. We examined the relationship between allostatic load, an index of peripheral biomarkers representing the cumulative effects of stress, and cortical thickness. Allostatic load was calculated for 44 patients with schizophrenia spectrum disorders (SSD) and 33 normal controls (NC) based on 13 cardiovascular, neuroendocrine, immune, and metabolic measurements. Controlling for age, SSD had significantly elevated allostatic load as compared with NC (p=0.008). Controlling for age, whole brain average cortical thickness was lower in SSD patients compared to NC (p=0.008). However, once allostatic load was accounted for, the group difference in cortical thickness became marginal (p=0.058). Exploratory analyses on subcomponents of allostatic load suggested that elevated immune marker C-reactive protein, stress hormones, and cardiovascular indices within allostatic load were more strongly associated with reduced cortical thickness in SSD. In NC, only the association between immune marker C-reactive protein and cortical thickness was replicated. These results support the hypothesis that allostatic load may account for some of the gray matter deficits observed in schizophrenia. Among the allostatic indices, the inflammatory mechanism appears particularly relevant to cortical thickness in both schizophrenia patients and normal controls.

A magnetic resonance imaging family study of cortical thickness in schizophrenia.

Schizophrenia is associated with abnormalities in cortical thickness, including both thicker and thinner cortices than controls. Although less reliably than in patients, non-psychotic relatives of schizophrenia patients have also demonstrated both thicker and thinner cortices than controls, suggesting an effect of familial or genetic liability. We investigated cortical thickness in 25 schizophrenia patients, 26 adult non-psychotic first-degree biological relatives, and 23 community controls using the automated program FreeSurfer. Contrary to hypotheses, we found relatives of schizophrenia patients had greater cortical thickness in all lobes compared to patients and controls; however, this finding was not as widespread when compared to controls. In contrast, schizophrenia patients only demonstrated a thinner right fusiform region than controls and relatives. Our finding of greater thickness in adult biological relatives could represent a maladaptive abnormality or alternatively, a compensatory mechanism. Previous literature suggests that the nature of abnormalities in relatives can vary by the age of relatives and change across the developmental period. Abnormalities in patients may depend on lifestyle factors and on current and previous anti-psychotic medication use. Our results speak to the need to study various populations of patients and relatives across the lifespan to better understand different developmental periods and the impact of environmental factors. © 2015 Wiley Periodicals, Inc.

PRODH Polymorphisms, Cortical Volumes and Thickness in Schizophrenia

Schizophrenia is a neurodevelopmental disorder with high heritability. Several lines of evidence indicate that the PRODH gene may be related to the disorder. Therefore, our study investigates the effects of 12 polymorphisms of PRODH on schizophrenia and its phenotypes. To further evaluate the roles of the associated variants in the disorder, we have conducted magnetic resonance imaging (MRI) scans to assess cortical volumes and thicknesses. A total of 192 patients were evaluated using the Structured Clinical Interview for DSM-IV (SCID), Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale, Global Assessment of Functioning (GAF) and Clinical Global Impression (CGI) instruments. The study included 179 controls paired by age and gender. The samples were genotyped using the real-time polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP)-PCR and Sanger sequencing methods. A sample of 138 patients and 34 healthy controls underwent MRI scans. One polymorphism was associated with schizophrenia (rs2904552), with the G-allele more frequent in patients than in controls. This polymorphism is likely functional, as predicted by PolyPhen and SIFT, but it was not associated with brain morphology in our study. In summary, we report a functional PRODH variant associated with schizophrenia that may have a neurochemical impact, altering brain function, but is not responsible for the cortical reductions found in the disorder.

ZNF804A and cortical thickness in schizophrenia and bipolar disorder

ZNF804A SNP rs1344706 confers genome-wide risk for schizophrenia and bipolar disorder. Both disorders affect cortical thickness. To determine if single nucleotide polymorphisms (SNPs) across ZNF804A are associated with cortical thinning, we investigated 63 SNPs (including rs1344706) in 365 psychosis patients and healthy controls. Results show no significant associations.

Temporal and frontal cortical thickness associations with M100 auditory activity and attention in healthy controls and individuals with schizophrenia

BackgroundAlthough gray matter (GM) abnormalities are frequently observed in individuals with schizophrenia (SCZ), the functional consequences of these structural abnormalities are not yet understood. The present study sought to better understand GM abnormalities in SCZ by examining associations between GM and two putative functional SCZ biomarkers: weak 100ms (M100) auditory responses and impairment on tests of attention. MethodsData were available from 103 subjects (healthy controls=52, SCZ=51). GM cortical thickness measures were obtained for superior temporal gyrus (STG) and prefrontal cortex (PFC). Magnetoencephalography (MEG) provided measures of left and right STG M100 source strength. Subjects were administered the Trail Making Test A and the Connors' Continuous Performance Test to assess attention. ResultsA strong trend indicated less GM cortical thickness in SCZ than controls in both regions and in both hemispheres (p=0.06). Individuals with SCZ had weaker M100 responses than controls bilaterally, and individuals with SCZ performed more poorly than controls on tests of attention. Across groups, left STG GM was positively associated with left M00 source strength. In SCZ only, less left and right STG and PFC GM predicted poorer performance on tests of attention. After removing variance in attention associated with age, associations between GM and attention remained significant only in left and right STG. ConclusionsReduced GM cortical thickness may serve as a common substrate for multiple functional abnormalities in SCZ, with structural–functional abnormalities in STG GM especially prominent. As suggested by others, functional abnormalities in SCZ may be a consequence of elimination of the neuropil (dendritic arbors and associated synaptic infrastructure) between neuron bodies.

Changes in cortical thickness in the frontal lobes in schizophrenia are a result of thinning of pyramidal cell layers

Decreased cortical thickness and reduced activity as measured by fMRI in the grey matter of the subgenual cingulate cortex have been reported in schizophrenia and bipolar disorder, and cortical grey matter loss has been reliably reported in the frontal and temporal lobes in schizophrenia. The aim of this study was to examine the thickness of each of the six cortical layers in the subgenual cingulate cortex, five frontal lobe and four temporal lobe gyri. We examined two separate cohorts. Cohort 1 examines the subgenual cingulate cortex (SCC) in schizophrenia (n = 10), bipolar disorder (n = 15) and major depressive disorder (n = 20) against control subjects (n = 19). Cohort two examines frontal and temporal gyri in schizophrenia (n = 16), major depressive disorder (n = 6) against matched controls (n = 32). The cohorts were selected with identical clinical criteria, but underwent different tissue processing to contrast the effect of chemical treatment on tissue shrinkage. Measurements of layer I-VI thickness were taken from cresyl-violet- and haematoxylin-stained sections in cohort one and from cresyl-violet- and H&E-stained sections in cohort two. SCC cortical thickness decreased in male subjects with bipolar disorder (p = 0.048), and male schizophrenia cases showed a specific decrease in the absolute thickness of layer V (p = 0.003). Compared to controls, the relative thickness of layer V in the crown of the SCC decreased in schizophrenia (p < 0.001). A significant decrease in total cortical thickness was observed across the frontal lobe in schizophrenia (p < 0.0001), with specific pyramidal layer thinning in layers III (p = 0.0001) and V (p = 0.005). There was no effect of lateralization. No changes were noted in temporal lobe cortical thickness. This study demonstrates diminished pyramidal layer thickness resulting in decreased frontal lobe thickness in schizophrenia.

Cortical Volume, Surface Area, and Thickness in Schizophrenia and Bipolar Disorder

Magnetic resonance imaging studies have shown that structural brain abnormalities are present in both schizophrenia and bipolar disorder. Most previous studies have focused on brain tissue volumes, but advances in neuroimaging data processing have made it possible to separate cortical area and cortical thickness. The purpose of the present study was to provide a more complete picture of cortical morphometric differences in schizophrenia and bipolar disorder, decomposing cortical volume into its constituent parts, cortical thickness and cortical area. We analyzed magnetic resonance imaging images from a sample of 173 patients with schizophrenia, 139 patients with bipolar disorder, and 207 healthy control subjects. Maps of cortical volume, area, and thickness across the continuous cortical surface were generated within groups and compared between the groups. There were widespread reductions in cortical volume in schizophrenia relative to healthy control subjects and patients with bipolar disorder type I. These reductions were mainly driven by cortical thinning, but there were also cortical area reductions in more circumscribed regions, which contributed to the observed volume reductions. The current surface-based methodology allows for a distinction between cortical thinning and reduction in cortical area and reveals that cortical thinning is the most important factor in volume reduction in schizophrenia. Cortical area reduction was not observed in bipolar disorder type I and may be unique to schizophrenia.