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Multivariate Relationships Between Cognition and Brain Anatomy Across the Psychosis Spectrum.

ABSTRACT: BACKGROUND:Cognitive and structural brain abnormalities range from mild to severe in psychosis. The relationships of specific cognitive functions to specific brain structures across the psychosis spectrum is less certain. METHODS:Participants (n = 678) with bipolar, schizoaffective, or schizophrenia psychoses and healthy control subjects were recruited via the Bipolar-Schizophrenia Network for Intermediate Phenotypes. The Schizo-Bipolar Scale was used to create a psychosis continuum (from purely affective to purely nonaffective). Canonical correlation between 14 cognitive measures and structural brain measures (gray matter volume, cortical thickness, cortical surface area, and local gyrification indices) for 68 neocortical regions yielded constructs that defined shared cognition-brain structure relationships. Canonical discriminant analysis was used to integrate these constructs and efficiently summarize cognition-brain structure relationships across the psychosis continuum. RESULTS:General cognition was associated with larger gray matter volumes and thicker cortices but smaller cortical surface area in frontoparietal regions. Working memory was associated with larger volume and surface area in frontotemporal regions. Faster response speed was associated with thicker frontal cortices. Constructs that captured general cognitive ability and working memory and their relationship to cortical volumes primarily defined an ordered psychosis spectrum (purely affective, least abnormal through purely nonaffective, and most abnormal). A construct that captured general cognitive ability and its relationship to cortical surface area differentiated purely affective cases from other groups. CONCLUSIONS:General cognition and working memory with cortical volume deviations characterized more nonaffective psychoses. Alternatively, affective psychosis cases with general cognitive deficits had deviations in cortical surface area, perhaps accounting for heterogeneous findings across previous studies.

SUBMITTER: Rodrigue AL

PROVIDER: S-EPMC6167203 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Multivariate Relationships Between Cognition and Brain Anatomy Across the Psychosis Spectrum.

Rodrigue Amanda L AL McDowell Jennifer E JE Tandon Neeraj N Keshavan Matcheri S MS Tamminga Carol A CA Pearlson Godfrey D GD Sweeney John A JA Gibbons Robert D RD Clementz Brett A BA

Biological psychiatry. Cognitive neuroscience and neuroimaging 20180331 12

<h4>Background</h4>Cognitive and structural brain abnormalities range from mild to severe in psychosis. The relationships of specific cognitive functions to specific brain structures across the psychosis spectrum is less certain.<h4>Methods</h4>Participants (n = 678) with bipolar, schizoaffective, or schizophrenia psychoses and healthy control subjects were recruited via the Bipolar-Schizophrenia Network for Intermediate Phenotypes. The Schizo-Bipolar Scale was used to create a psychosis continu ...[more]

PMID: 29759822

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Project description:Elevations in peripheral inflammatory markers have been reported in patients with psychosis. Whether this represents an inflammatory process defined by individual or subgroups of markers is unclear. Further, relationships between peripheral inflammatory marker elevations and brain structure, cognition, and clinical features of psychosis remain unclear. We hypothesized that a pattern of plasma inflammatory markers, and an inflammatory subtype established from this pattern, would be elevated across the psychosis spectrum and associated with cognition and brain structural alterations. Clinically stable psychosis probands (Schizophrenia spectrum, n = 79; Psychotic Bipolar disorder, n = 61) and matched healthy controls (HC, n = 60) were assessed for 15 peripheral inflammatory markers, cortical thickness, subcortical volume, cognition, and symptoms. A combination of unsupervised exploratory factor analysis and hierarchical clustering was used to identify inflammation subtypes. Levels of IL6, TNFα, VEGF, and CRP were significantly higher in psychosis probands compared to HCs, and there were marker-specific differences when comparing diagnostic groups. Individual and/or inflammatory marker patterns were associated with neuroimaging, cognition, and symptom measures. A higher inflammation subgroup was defined by elevations in a group of 7 markers in 36% of Probands and 20% of HCs. Probands in the elevated inflammatory marker group performed significantly worse on cognitive measures of visuo-spatial working memory and response inhibition, displayed elevated hippocampal, amygdala, putamen and thalamus volumes, and evidence of gray matter thickening compared to the proband group with low inflammatory marker levels. These findings specify the nature of peripheral inflammatory marker alterations in psychotic disorders and establish clinical, neurocognitive and neuroanatomic associations with increased inflammatory activation in psychosis. The identification of a specific subgroup of patients with inflammatory alteration provides a potential means for targeting treatment with anti-inflammatory medications.

Project description:BackgroundNeuropsychological deficits are a core feature of established psychosis and have been previously linked to fronto-temporo-limbic brain alterations. Both neurocognitive and neuroanatomical abnormalities characterize clinical at-risk mental states (ARMS) for psychosis. However, structure-cognition relationships in the ARMS have not been directly explored using multivariate neuroimaging techniques.MethodsVoxel-based morphometry and partial least squares were employed to study system-level covariance patterns between whole-brain morphological data and processing speed, working memory, verbal learning/IQ, and executive functions in 40 ARMS subjects and 30 healthy controls (HC). The detected structure-cognition covariance patterns were tested for significance and reliability using non-parametric permutation and bootstrap resampling.ResultsWe identified ARMS-specific covariance patterns that described a generalized association of neurocognitive measures with predominantly prefronto-temporo-limbic and subcortical structures as well as the interconnecting white matter. In the conversion group, this generalized profile particularly involved working memory and verbal IQ and was positively correlated with limbic, insular and subcortical volumes as well as negatively related to prefrontal, temporal, parietal, and occipital cortices. Conversely, the neurocognitive profiles in the HC group were confined to working memory, learning and IQ, which were diffusely associated with cortical and subcortical brain regions.ConclusionsThese findings suggest that the ARMS and prodromal phase of psychosis are characterized by a convergent mapping from multi-domain neurocognitive measures to a set of prefronto-temporo-limbic and subcortical structures. Furthermore, a neuroanatomical separation between positive and negative brain-cognition correlations may not only point to a biological process determining the clinical risk for disease transition, but also to possible compensatory or dysmaturational neural processes.

Project description:Linking structural neuroimaging data from multiple modalities to cognitive performance is an important challenge for cognitive neuroscience. In this study we examined the relationship between verbal fluency performance and neuroanatomy in 54 patients with frontotemporal degeneration (FTD) and 15 age-matched controls, all of whom had T1- and diffusion-weighted imaging. Our goal was to incorporate measures of both gray matter (voxel-based cortical thickness) and white matter (fractional anisotropy) into a single statistical model that relates to behavioral performance. We first used eigenanatomy to define data-driven regions of interest (DD-ROIs) for both gray matter and white matter. Eigenanatomy is a multivariate dimensionality reduction approach that identifies spatially smooth, unsigned principal components that explain the maximal amount of variance across subjects. We then used a statistical model selection procedure to see which of these DD-ROIs best modeled performance on verbal fluency tasks hypothesized to rely on distinct components of a large-scale neural network that support language: category fluency requires a semantic-guided search and is hypothesized to rely primarily on temporal cortices that support lexical-semantic representations; letter-guided fluency requires a strategic mental search and is hypothesized to require executive resources to support a more demanding search process, which depends on prefrontal cortex in addition to temporal network components that support lexical representations. We observed that both types of verbal fluency performance are best described by a network that includes a combination of gray matter and white matter. For category fluency, the identified regions included bilateral temporal cortex and a white matter region including left inferior longitudinal fasciculus and frontal-occipital fasciculus. For letter fluency, a left temporal lobe region was also selected, and also regions of frontal cortex. These results are consistent with our hypothesized neuroanatomical models of language processing and its breakdown in FTD. We conclude that clustering the data with eigenanatomy before performing linear regression is a promising tool for multimodal data analysis.

Project description:ImportanceStructural brain abnormalities are prominent in psychotic disorders, including schizophrenia. However, it is unclear when aberrations emerge in the disease process and if such deficits are present in association with less severe psychosis spectrum (PS) symptoms in youth.ObjectiveTo investigate the presence of structural brain abnormalities in youth with PS symptoms.Design, setting, and participantsThe Philadelphia Neurodevelopmental Cohort is a prospectively accrued, community-based sample of 9498 youth who received a structured psychiatric evaluation. A subsample of 1601 individuals underwent neuroimaging, including structural magnetic resonance imaging, at an academic and children's hospital health care network between November 1, 2009, and November 30, 2011.Main outcomes and measuresMeasures of brain volume derived from T1-weighted structural neuroimaging at 3 T. Analyses were conducted at global, regional, and voxelwise levels. Regional volumes were estimated with an advanced multiatlas regional segmentation procedure, and voxelwise volumetric analyses were conducted as well. Nonlinear developmental patterns were examined using penalized splines within a general additive model. Psychosis spectrum (PS) symptom severity was summarized using factor analysis and evaluated dimensionally.ResultsFollowing exclusions due to comorbidity and image quality assurance, the final sample included 791 participants aged youth 8 to 22 years. Fifty percent (n = 393) were female. After structured interviews, 391 participants were identified as having PS features (PS group) and 400 participants were identified as typically developing comparison individuals without significant psychopathology (TD group). Compared with the TD group, the PS group had diminished whole-brain gray matter volume (P = 1.8 × 10-10) and expanded white matter volume (P = 2.8 × 10-11). Voxelwise analyses revealed significantly lower gray matter volume in the medial temporal lobe (maximum z score = 5.2 and cluster size of 1225 for the right and maximum z score = 4.5 and cluster size of 310 for the left) as well as in frontal, temporal, and parietal cortex. Volumetric reduction in the medial temporal lobe was correlated with PS symptom severity.Conclusions and relevanceStructural brain abnormalities that have been commonly reported in adults with psychosis are present early in life in youth with PS symptoms and are not due to medication effects. Future longitudinal studies could use the presence of such abnormalities in conjunction with clinical presentation, cognitive profile, and genomics to predict risk and aid in stratification to guide early interventions.

Project description:IntroductionThe barrier function of the gut is important for many organs and systems, including the brain. If gut permeability increases, bacterial fragments may enter the circulation, giving rise to increased systemic inflammation. Increases in bacterial translocation are reflected in higher values of blood markers, including lipopolysaccharide binding protein (LBP) and soluble cluster of differentiation 14 (sCD14). Some pioneer studies showed a negative association between bacterial translocation markers and brain volumes, but this association remains scarcely investigated. We investigate the effect of bacterial translocation on brain volumes and cognition in both healthy controls and patients with a schizophrenia spectrum disorder (SSD).Materials and methodsHealthy controls (n = 39) and SSD patients (n = 72) underwent an MRI-scan, venipuncture and cognition assessments. We investigated associations between LBP and sCD14 and brain volumes (intracranial volume, total brain volume, and hippocampal volume) using linear regression. We then associated LBP and sCD14 to cognitive function using a mediation analysis, with intracranial volume as mediator.ResultsHealthy controls showed a negative association between hippocampal volume and LBP (b = -0.11, p = .04), and intracranial volume and sCD14 (b = -0.25, p = .07). Both markers were indirectly associated with lower cognitive functioning in healthy controls (LBP: b = -0.071, p = .028; sCD14: b = -0.213, p = .052), mediated by low intracranial volume. In the SSD patients, these associations were markedly less present.ConclusionThese findings extend earlier studies suggesting that increased bacterial translocation may negatively affect brain volume, which indirectly impacts cognition, even in this young healthy group. If replicated, this finding stresses the importance of a healthy gut for the development and optimal functioning of the brain. Absence of these associations in the SSD group may indicate that other factors such as allostatic load, chronic medication use and interrupted educational carrier had larger impact and attenuated the relative contribution of bacterial translocation.

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Multivariate Relationships Between Cognition and Brain Anatomy Across the Psychosis Spectrum.

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Multivariate Relationships Between Cognition and Brain Anatomy Across the Psychosis Spectrum.

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