Cerebral white matter structure is associated with DSM-5 schizophrenia symptom dimensions.
Ontology highlight
ABSTRACT:
SUBMITTER: Viher PV
PROVIDER: S-EPMC4925890 | biostudies-other | 2016
REPOSITORIES: biostudies-other
Publications
Cerebral white matter structure is associated with DSM-5 schizophrenia symptom dimensions.
Viher Petra V PV Stegmayer Katharina K Giezendanner Stéphanie S Federspiel Andrea A Bohlhalter Stephan S Vanbellingen Tim T Wiest Roland R Strik Werner W Walther Sebastian S
NeuroImage. Clinical 20160616
Diffusion tensor imaging (DTI) studies have provided evidence of widespread white matter (WM) abnormalities in schizophrenia. Although these abnormalities appear clinically significant, the relationship to specific clinical symptoms is limited and heterogeneous. This study examined the association between WM microstructure and the severity of the five main DSM-5 schizophrenia symptom dimensions. DTI was measured in forty patients with schizophrenia spectrum disorders. Using Tract-Based Spatial S ...[more]
Similar Datasets
Project description:Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for attention deficit/hyperactivity disorder (ADHD) specify two dimensions of inattention and hyperactivity-impulsivity symptoms that are used to define three nominal subtypes: predominantly hyperactive-impulsive type (ADHD-H), predominantly inattentive type (ADHD-I), and combined type (ADHD-C). To aid decision making for DSM-5 and other future diagnostic systems, a comprehensive literature review and meta-analysis of 546 studies was completed to evaluate the validity of the DSM-IV model of ADHD. Results indicated that DSM-IV criteria identify individuals with significant and persistent impairment in social, academic, occupational, and adaptive functioning when intelligence, demographic factors, and concurrent psychopathology are controlled. Available data overwhelmingly support the concurrent, predictive, and discriminant validity of the distinction between inattention and hyperactivity-impulsivity symptoms, and indicate that nearly all differences among the nominal subtypes are consistent with the relative levels of inattention and hyperactivity-impulsivity symptoms that define the subtypes. In contrast, the DSM-IV subtype model is compromised by weak evidence for the validity of ADHD-H after first grade, minimal support for the distinction between ADHD-I and ADHD-C in studies of etiological influences, academic and cognitive functioning, and treatment response, and the marked longitudinal instability of all three subtypes. Overall, we conclude that the DSM-IV ADHD subtypes provide a convenient clinical shorthand to describe the functional and behavioral correlates of current levels of inattention and hyperactivity-impulsivity symptoms, but do not identify discrete subgroups with sufficient long-term stability to justify the classification of distinct forms of the disorder. Empirical support is stronger for an alternative model that would replace the subtypes with dimensional modifiers that reflect the number of inattention and hyperactivity-impulsivity symptoms at the time of assessment. (PsycINFO Database Record (c) 2012 APA, all rights reserved).
| S-EPMC3622557 | biostudies-literature
Project description:Brain white matter abnormalities are evident in individuals with schizophrenia, and also their first-degree relatives, suggesting that some alterations may relate to underlying genetic risk. The ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) gene, which encodes the alpha-2,8-sialyltransferase 8B enzyme that aids neuronal migration and synaptic plasticity, was previously implicated as a schizophrenia susceptibility gene. This study examined the extent to which specific haplotypes in ST8SIA2 influence white matter microstructure using diffusion-weighted imaging of individuals with schizophrenia (n = 281) and healthy controls (n = 172), recruited across five Australian sites. Interactions between diagnostic status and the number of haplotype copies (0 or ≥1) were tested across all white matter voxels with cluster-based statistics. Fractional anisotropy (FA) in the right parietal lobe was found to show a significant interaction between diagnosis and ST8SIA2 protective haplotype (p < 0.05, family-wise error rate (FWER) cluster-corrected). The protective haplotype was associated with increased FA in controls, but this effect was reversed in people with schizophrenia. White matter fiber tracking revealed that the region-of-interest was traversed by portions of the superior longitudinal fasciculus, corona radiata, and posterior limb of internal capsule. Post hoc analysis revealed that reduced FA in this regional juncture correlated with reduced IQ in people with schizophrenia. The ST8SIA2 risk haplotype copy number did not show any differential effects on white matter. This study provides a link between a common disease-associated haplotype and specific changes in white matter microstructure, which may relate to resilience or risk for mental illness, providing further compelling evidence for involvement of ST8SIA2 in the pathophysiology of schizophrenia.
| S-EPMC5802561 | biostudies-literature
Project description:Understanding the neuroanatomical correlates of internalizing psychopathology during adolescence may shed light on to neurodevelopmental processes that make this a critical period for the trajectory of mental illness. However, few studies have simultaneously examined co-occurring and dissociable features of internalizing psychopathology during this formative developmental stage. In the current study we identify the neuroanatomical correlates of four dimensions of internalizing psychopathology symptoms in adolescents: a common internalizing dimension capturing covariance in symptoms across internalizing disorders, as well as low positive affect-, anxious arousal-, and anxious apprehension-specific residuals. Our results suggest that these dimensions are associated with neuroanatomy across much of the brain, including prefrontal and limbic regions implicated in case-control studies, but also regions supporting visual processing. Importantly, results differed between males and females in regions that are sexually dimorphic in adulthood and the direction of the effects were largely opposite to what has been observed in adults and children.
| S-EPMC9536530 | biostudies-literature
Project description:ImportanceSchizophrenia is a clinically heterogeneous disorder. It is currently unclear how variability in symptom dimensions and cognitive ability is associated with genetic liability for schizophrenia.ObjectiveTo determine whether phenotypic dimensions within schizophrenia are associated with genetic liability to schizophrenia, other neuropsychiatric disorders, and intelligence.Design, setting, and participantsIn a genetic association study, 3 cross-sectional samples of 1220 individuals with a diagnosis of schizophrenia were recruited from community, inpatient, and voluntary sector mental health services across the UK. Confirmatory factor analysis was used to create phenotypic dimensions from lifetime ratings of the Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, and the MATRICS Consensus Cognitive Battery. Analyses of polygenic risk scores (PRSs) were used to assess whether genetic liability to schizophrenia, other neuropsychiatric disorders, and intelligence were associated with these phenotypic dimensions. Data collection for the cross-sectional studies occurred between 1993 and 2016. Data analysis for this study occurred between January 2019 and March 2021.Main outcomes and measuresOutcome measures included phenotypic dimensions defined from confirmatory factor analysis relating to positive symptoms, negative symptoms of diminished expressivity, negative symptoms of motivation and pleasure, disorganized symptoms, and current cognitive ability. Exposure measures included PRSs for schizophrenia, bipolar disorder, major depression, attention-deficit/hyperactivity disorder, autism spectrum disorder, and intelligence.ResultsOf the 1220 study participants, 817 were men (67.0%). Participants' mean (SD) age at interview was 43.10 (12.74) years. Schizophrenia PRS was associated with increased disorganized symptom dimension scores in both a 5-factor model (β = 0.14; 95% CI, 0.07-0.22; P = 2.80 × 10-4) and a 3-factor model across all samples (β = 0.10; 95% CI, 0.05-0.15; P = 2.80 × 10-4). Current cognitive ability was associated with genetic liability to schizophrenia (β = -0.11; 95% CI, -0.19 to -0.04; P = 1.63 × 10-3) and intelligence (β = 0.23; 95% CI, 0.16-0.30; P = 1.52 × 10-10). After controlling for estimated premorbid IQ, current cognitive performance was associated with schizophrenia PRS (β = -0.08; 95% CI, -0.14 to -0.02; P = 8.50 × 10-3) but not intelligence PRS.Conclusions and relevanceThe findings of this study suggest that genetic liability for schizophrenia is associated with higher disorganized dimension scores but not other symptom dimensions. Cognitive performance in schizophrenia appears to reflect distinct contributions from genetic liabilities to both intelligence and schizophrenia.
| S-EPMC8340009 | biostudies-literature
Project description:The phosphatidylinositol 3-kinase (PI3K)-AKT signal transduction pathway is critical to cell growth and survival. In vitro functional studies indicate that the candidate schizophrenia susceptibility gene DTNBP1 influences AKT signaling to promote neuronal viability. The AKT1 gene has also been implicated in schizophrenia by association studies and decreased protein expression in the brains of schizophrenic patients.The association of DTNBP1 in the Irish Study of High Density Schizophrenia Families (ISHDSF) prompted our investigation of AKT1 for association with disease in this sample. Eight single nucleotide polymorphisms spanning AKT1 were analyzed for association with schizophrenia across four definitions of affection and according to Operational Criteria Checklist of Psychotic Illness (OPCRIT) symptom scales. We examined expression of AKT1 messenger RNA from postmortem brain tissue of schizophrenic, bipolar, and control individuals.No single marker showed significant association, but the risk haplotype previously found over-transmitted to Caucasian schizophrenic patients was significantly under-transmitted in the ISHDSF (.01 < p < .05), across all OPCRIT symptom dimensions. Exploratory haplotype analysis confirmed association with schizophrenia toward the 5' end of AKT1 (.008 < p < .049, uncorrected). We found significantly decreased RNA levels in prefrontal cortex of schizophrenic individuals, consistent with reduced AKT1 protein levels reported in schizophrenic brain.The replication of association of AKT1 gene variants in a further Caucasian family sample adds support for involvement of AKT signaling in schizophrenia, perhaps encompassing a broader clinical phenotype that includes mood dysregulation. We show that AKT signaling might be compromised in schizophrenic and bipolar patients via reduced RNA expression of specific AKT isoforms.
| S-EPMC2441648 | biostudies-literature
Project description:Elevated rate of aging-related biological and functional decline, termed "accelerated aging," is reported in patients with schizophrenia (SCZ) and major depressive disorder (MDD). We used diffusion tensor imaging derived fractional anisotropy (FA) as a biomarker of aging-related decline in white matter (WM) integrity to test the hypotheses of accelerated aging in SCZ and MDD.The SCZ cohort comprised 58 SCZ patients and 60 controls (aged 20-60 years). The MDD cohort comprised 136 MDD patients and 351 controls (aged 20-79 years). The main outcome measures were the diagnosis-by-age interaction on whole-brain-averaged WM FA values and FA values from 12 major WM tracts.Diagnosis-by-age interaction for the whole-brain average FA was significant for the SCZ (p = .04) but not the MDD (p = .80) cohort. Diagnosis-by-age interaction was nominally significant (p<.05) for five WM tracts for SCZ and for none of the tracts in the MDD cohort. Tract-specific heterochronicity of the onset of age-related decline in SCZ demonstrated strong negative correlations with the age-of-peak myelination and the rates of age-related decline obtained from normative sample (r =-.61 and-.80, p<.05, respectively). No such trends existed for MDD cohort.Cerebral WM showed accelerated aging in SCZ but not in MDD, suggesting some difference in the pathophysiology underlying their WM aging changes. Tract-specific heterochronicity of WM development modulated presentation of accelerated aging in SCZ: WM tracts that matured later in life appeared more sensitive to the pathophysiology of SCZ and demonstrated more susceptibility to disorder-related accelerated decline in FA values with age. This trend was not observed in MDD cohort.
| S-EPMC3645491 | biostudies-literature
Project description:Background and purposePrevious studies have shown that diffusion tensor imaging suggests a diffuse loss of white matter integrity in people with white matter hyperintensities or lacunes. The purpose of this study was to investigate whether the presence of cerebral microbleeds and their distribution are related to the integrity of white matter microstructures.Materials and methodsThe study comprised 982 participants who underwent brain MR imaging to determine microbleed status. The cross-sectional relation between microbleeds and the microstructural integrity of the white matter was assessed by 2 statistical methods: a multilinear regression model based on the average DTI parameters of normal-appearing white matter and Tract-Based Spatial Statistics analysis, a tract-based voxelwise analysis. Fiber tractography was used to spatially describe the microstructural abnormalities along WM tracts containing a cerebral microbleed.ResultsThe presence of cerebral microbleeds was associated with lower mean fractional anisotropy and higher mean diffusivity, axial diffusivity, and radial diffusivity, and the association remained when cardiovascular risk factors and cerebral small-vessel disease markers were further adjusted. Tract-Based Spatial Statistics analysis indicated strictly lobar cerebral microbleeds associated with lower fractional anisotropy, higher mean diffusivity, and higher radial diffusivity in the internal capsule and corpus callosum after adjusting other cerebral small-vessel disease markers, while only a few voxels remained associated with deep cerebral microbleeds. Diffusion abnormalities gradients along WM tracts containing a cerebral microbleed were not found in fiber tractography analysis.ConclusionsCerebral microbleeds are associated with widely distributed changes in white matter, despite their focal appearance on SWI.
| S-EPMC7658876 | biostudies-literature
Project description:White matter hyperintensities (WMH) in elderly individuals with vascular diseases are presumed to be due to ischemic small vessel diseases; however, their etiology is unknown. We examined the cross-sectional relationship between cerebrovascular hemodynamics and white matter structural integrity in elderly individuals with vascular risk factors. White matter hyperintensity volumes, fractional anisotropy (FA), and mean diffusivity (MD) were obtained from MRI in 48 subjects (75±7years). Pulsatility index (PI) and dynamic cerebral autoregulation (dCA) was assessed using transcranial Doppler ultrasound of the middle cerebral artery. Dynamic cerebral autoregulation was calculated from transfer function analysis (phase and gain) of spontaneous blood pressure and flow velocity oscillations in the low (LF, 0.03 to 0.15 Hz) and high (HF, 0.16 to 0.5 Hz) frequency ranges. Higher PI was associated with greater WMH (P<0.005). Higher phase across all frequency ranges was associated with greater FA and lower MD (P<0.005). Lower gain was associated with higher FA in the LF range (P=0.001). These relationships between phase and FA were significant in the territories limited to the middle cerebral artery as well as across the entire brain. Our results show a strong relationship between impaired cerebrovascular hemodynamics (PI and dCA) and loss of cerebral white matter structural integrity (WMH and DTI metrics) in elderly individuals.
| S-EPMC3915198 | biostudies-literature
Project description:INTRODUCTION:Structural alterations may correlate with symptom severity in psychotic disorders, but the existing literature on this issue is heterogeneous. In addition, it is not known how cortical thickness and cortical surface area correlate with symptom dimensions of psychosis. METHODS:Subjects included 455 individuals with schizophrenia, schizoaffective, or bipolar I disorders. Data were obtained as part of the Bipolar Schizophrenia Network for Intermediate Phenotypes study. Diagnosis was made through the Structured Clinical Interview for DSM-IV. Positive and negative symptom subscales were assessed using the Positive and Negative Syndrome Scale. Structural brain measurements were extracted from T1-weight structural MRIs using FreeSurfer v5.1 and were correlated with symptom subscales using partial correlations. Exploratory factor analysis was also used to identify factors among those regions correlating with symptom subscales. RESULTS:The positive symptom subscale correlated inversely with gray matter volume (GMV) and cortical thickness in frontal and temporal regions, whereas the negative symptom subscale correlated inversely with right frontal cortical surface area. Among regions correlating with the positive subscale, factor analysis identified four factors, including a temporal cortical thickness factor and frontal GMV factor. Among regions correlating with the negative subscale, factor analysis identified a frontal GMV-cortical surface area factor. There was no significant diagnosis by structure interactions with symptom severity. CONCLUSIONS:Structural measures correlate with positive and negative symptom severity in psychotic disorders. Cortical thickness demonstrated more associations with psychopathology than cortical surface area.
| S-EPMC4266291 | biostudies-literature
Project description:ObjectiveFailure of antipsychotic medications to resolve symptoms in patients with schizophrenia creates a clinical challenge that is known as treatment resistance. The causes of treatment resistance are unknown, but it is associated with earlier age at onset and more severe cognitive deficits. The authors tested the hypothesis that white matter deficits that are involved in both neurodevelopment and severity of cognitive deficits in schizophrenia are associated with a higher risk of treatment resistance.MethodsThe study sample (N=122; mean age, 38.2 years) included schizophrenia patients at treatment initiation (N=45), patients whose symptoms were treatment responsive (N=40), and patients whose symptoms were treatment resistant (N=37), as well as healthy control subjects (N=78; mean age, 39.2 years). White matter regional vulnerability index (RVI) was tested as a predictor of treatment resistance and cognitive deficits. Higher RVI is indicative of better agreement between diffusion tensor imaging fractional anisotropy across the brain in an individual and the pattern identified by the largest-to-date meta-analysis of white matter deficits in schizophrenia.ResultsPatients with treatment-resistant symptoms showed the highest white matter RVI (mean=0.38 [SD=0.2]), which was significantly higher than the RVI among patients with treatment-responsive symptoms (mean=0.30 [SD=0.02]). At the onset of treatment, schizophrenia patients showed significantly higher RVI than healthy control subjects (mean=0.18 [SD=0.03] and mean=0.13 [SD=0.02], respectively). RVIs were significantly correlated with performance on processing speed and negative symptoms.ConclusionsSchizophrenia affects white matter microstructure in specific regional patterns. Susceptibility to white matter regional deficits is associated with an increased likelihood of treatment resistance. Developments to overcome schizophrenia treatment resistance should consider white matter as an important target.
| S-EPMC6773514 | biostudies-literature