Relationship between neuropsychological behavior and brain white matter in first-episode psychosis.
Ontology highlight
ABSTRACT:
SUBMITTER: Faria AV
PROVIDER: S-EPMC6544495 | biostudies-literature | 2019 Jun
REPOSITORIES: biostudies-literature
Publications
Relationship between neuropsychological behavior and brain white matter in first-episode psychosis.
Faria Andreia V AV Crawford Jeffrey J Ye Chenfei C Hsu Johnny J Kenkare Anshel A Schretlen David D Sawa Akira A
Schizophrenia research 20190413
We addressed the relationship between white matter architecture, represented by MRI fractional anisotropy (FA), and cognition in individuals with first-episode psychosis (FEP) by applying for a new methodology that allows whole brain parcellation of core and peripheral white matter in a biologically meaningful fashion. Regionally specific correlations were found in FEP between three specific domains of cognition (processing speed, attention/working memory, and executive functioning) and FA at th ...[more]
Similar Datasets
Project description:White-matter hyperintensities have been associated with both schizophrenia and mood disorders, particularly bipolar disorder, but results are inconsistent across studies.To examine whether white-matter hyperintensities are a vulnerability marker for psychosis or are specifically associated with bipolar disorder.T(2)-weighted magnetic resonance imaging data were acquired in 129 individuals with first-episode psychosis (either affective or non-affective psychoses) and 102 controls who were randomly selected from the same geographical areas. Visual white-matter hyperintensity ratings were used for group and subgroup comparisons.There were no statistically significant between-group differences in white-matter hyperintensity frequency or severity scores. No significant correlations were found between white-matter hyperintensity scores and duration of illness, duration of untreated psychosis, or severity of psychotic, manic or depressive symptoms.White-matter hyperintensities are not associated with vulnerability to psychosis in general, or specifically with affective psychoses. Further, first-episode psychosis investigations using more quantitative methods are warranted to confirm these findings.
| S-EPMC2802525 | biostudies-other
Project description:The integrity of brain white matter connections is central to a patient's ability to respond to pharmacological interventions. This study tested this hypothesis using a specific measure of white matter integrity, and examining its relationship to treatment response using a prospective design in patients within their first episode of psychosis. Diffusion tensor imaging data were acquired in 63 patients with first episode psychosis and 52 healthy control subjects (baseline). Response was assessed after 12 weeks and patients were classified as responders or non-responders according to treatment outcome. At this second time-point, they also underwent a second diffusion tensor imaging scan. Tract-based spatial statistics were used to assess fractional anisotropy as a marker of white matter integrity. At baseline, non-responders showed lower fractional anisotropy than both responders and healthy control subjects (P < 0.05; family-wise error-corrected), mainly in the uncinate, cingulum and corpus callosum, whereas responders were indistinguishable from healthy control subjects. After 12 weeks, there was an increase in fractional anisotropy in both responders and non-responders, positively correlated with antipsychotic exposure. This represents one of the largest, controlled investigations of white matter integrity and response to antipsychotic treatment early in psychosis. These data, together with earlier findings on cortical grey matter, suggest that grey and white matter integrity at the start of treatment is an important moderator of response to antipsychotics. These findings can inform patient stratification to anticipate care needs, and raise the possibility that antipsychotics may restore white matter integrity as part of the therapeutic response.
| S-EPMC3891445 | biostudies-literature
Project description:It is becoming increasingly clear that longer duration of untreated psychosis (DUP) is associated with adverse clinical outcomes in patients with psychosis spectrum disorders. Because this association is often cited when justifying early intervention efforts, it is imperative to better understand underlying biological mechanisms. We enrolled 66 antipsychotic-naïve first-episode psychosis (FEP) patients and 45 matched healthy controls in this trial. At baseline, we used a human connectome style diffusion-weighted imaging (DWI) sequence to quantify white matter integrity in both groups. Patients then received 16 weeks of treatment with risperidone, 51 FEP completed the trial. We compared whole-brain fractional anisotropy (FA), mean diffusivity, axial diffusivity (AD), and radial diffusivity between groups. To test if structural white matter integrity mediates the relationship between longer DUP and poorer treatment response, we fit a mediator model and estimated indirect effects. We found decreased whole-brain FA and AD in medication-naive FEP compared with controls. In patients, lower FA was correlated with longer DUP (r = -0.32; p = 0.03) and poorer subsequent response to antipsychotic treatment (r = 0.40; p = 0.01). Importantly, we found a significant mediation effect for FA (indirect effect: -2.70; p = 0.03), indicating that DUP exerts its effects on treatment response through affecting white matter integrity. Our data provide empirical support to the idea the DUP may have fundamental pathogenic effects on the natural history of psychosis, suggest a biological mechanism underlying this phenomenon, and underscore the importance of early intervention efforts in this disabling neuropsychiatric syndrome.
| S-EPMC7658031 | biostudies-literature
Project description:Disrupted thalamo-cortical connectivity is regarded as a core psychopathology in patients diagnosed with schizophrenia. However, whether the thalamo-cortical white matter connectivity is disrupted before the onset of psychosis is still unknown. To determine this gap in knowledge, the strength of thalamo-cortical white matter anatomical connectivity in subjects at clinical-high risk for psychosis (CHR) was compared to that of first-episode psychosis (FEP) and healthy controls. A total of 37 CHR, 21 FEP, and 37 matched healthy controls underwent diffusion-weighted magnetic resonance imaging to examine the number of probabilistic tractography "counts" representing thalamo-cortical white matter connectivity. We also investigated the relationship with psychopathology. For FEP, the connectivity between the thalamus and parietal cortex was significantly increased (F= 5.65,P< .05) compared to that of healthy controls. However, the connectivity between thalamus and orbitofrontal cortex was significantly reduced compared to both healthy controls (F= 11.86,P< .005) and CHR (F= 6.63,P< .05). Interestingly, CHR exhibited a similar pattern as FEP, albeit with slightly reduced magnitude. Compared to healthy controls, there was a significant decrease (F= 4.16,P< .05) in CHR thalamo-orbitofrontal connectivity. Also, the strength of the thalamo-orbitofrontal connectivity was correlated with the Global Assessment of Functioning score in CHR (r= .35,P< .05). This observed pattern of white matter connectivity disruptions in FEP and in CHR suggests that this pattern of disconnectivity not only highlights the involvement of thalamus but also might be useful as an early biomarker for psychosis.
| S-EPMC4838094 | biostudies-literature
Project description:First-episode psychosis (FEP) is associated with inflammatory and brain structural changes, but few studies have investigated whether systemic inflammation associates with brain structural changes in FEP. Thirty-seven FEP patients (median 27 days on antipsychotic medication), and 19 matched controls were recruited. Serum levels of 38 chemokines and cytokines, and cardiovascular risk markers were measured at baseline and 2 months later. We collected T1- and diffusion-weighted MRIs with a 3 T scanner from the patients at baseline. We analyzed the association of psychosis-related inflammatory markers with gray and white matter (WM) volume using voxel-based morphometry and WM diffusion using tract-based spatial statistics with whole-brain and region-of-interest (ROI) analyses. FEP patients had higher CCL22 and lower TGF?, CXCL1, CCL7, IFN-?2 and ApoA-I than controls. CCL22 decreased significantly between baseline and 2 months in patients but was still higher than in controls. The association between inflammatory markers and FEP remained significant after adjusting for age, sex, smoking and BMI. We did not observe a correlation of inflammatory markers with any symptoms or duration of antipsychotic treatment. Baseline CCL22 levels correlated negatively with WM volume and positively with mean diffusivity and radial diffusivity bilaterally in the frontal lobes in ROI analyses. Decreased serum level of ApoA-I was associated with smaller volume of the medial temporal WM. In whole-brain analyses, CCL22 correlated positively with mean diffusivity and radial diffusivity, and CXCL1 associated negatively with fractional anisotropy and positively with mean diffusivity and radial diffusivity in several brain regions. This is the first report to demonstrate an association between circulating chemokine levels and WM in FEP patients. Interestingly, CCL22 has been previously implicated in autoimmune diseases associated with WM pathology. The results suggest that an altered activation of innate immunity may contribute to WM damage in psychotic disorders.
| S-EPMC4430522 | biostudies-literature
Project description:Jumping to conclusions (JTC) and impaired social cognition (SC) affect the decoding, processing, and use of social information by people with psychosis. However, the relationship between them had not been deeply explored within psychosis in general, and in first-episode psychosis (FEP) in particular. Our aim was to study the relationship between JTC and SC in a sample with FEP. We conducted a cross-sectional study with 121 patients with FEP, with measures to assess JTC (easy, hard, and salient probability tasks) and SC (emotional recognition, attributional style, and theory of mind). We performed Student's t-test and logistic regression in order to analyse these associations.We found a statistically significant and consistent relationship of small-moderate effect size between JTC (all three tasks) and impaired emotional recognition. Also, our results suggest a relationship between JTC and internal attributions for negative events. Relationships between JTC and theory of mind were not found. These results highlight the importance of psychological treatments oriented to work on a hasty reasoning style and on improving processing of social information linked to emotional recognition and single-cause attributions.
| S-EPMC9261088 | biostudies-literature
Project description:The deficit syndrome is thought to be a more homogenous clinical subgroup within the syndrome of schizophrenia that is characterized by enduring negative symptoms. It is hypothesized that distinct pathophysiological processes underlie the subtypes, where the deficit syndrome reflects an early onset nonprogressive developmental process, and the nondeficit form of the illness is characterized by attenuated neuroplasticity secondary to elevated glutamate levels. We used single-voxel magnetic resonance spectroscopy (PRESS; TE: 30 ms) to measure left frontal white matter neurometabolite levels in 61 antipsychotic-naïve first-episode psychosis patients (39 who did not display deficit features, 22 who did display deficit features, assessed with the Schedule for the Deficit Syndrome) and 59 healthy controls. Metabolite levels were quantified with the LCModel. We used a MANCOVA to determine neurometabolite differences between healthy controls, deficit syndrome patients, and nondeficit patients. We report a significant group difference when all metabolites were considered jointly (F[10,208] = 2.16; P = .02). Post hoc analyses showed that patients presenting without deficit features had higher glutamate levels than patients with deficit features and controls. Patients presenting without deficit features also had significantly higher myoinositol levels than controls; myoinositol levels were trend-level higher in patients presenting with deficit features compared to controls. Our data support the idea that the pathophysiology of patients presenting without deficit features may differ from those presenting with deficit features.
| S-EPMC8266628 | biostudies-literature
Project description:Analyzing the schizophrenia connectome can identify illness-related alterations in connectivity across the brain. An important question that remains unanswered is whether connectivity alterations are already evident at the onset of illness, before treatment with antipsychotic medication and possible influences of neuroprogressive or secondary alterations related to chronic illness duration. In the present study, diffusion tensor imaging and deterministic fiber tractography were performed with 137 antipsychotic-naive first-episode schizophrenia patients and 113 matched healthy controls. Using graph theoretic analysis, groups were compared in global and regional measurements and modularity of white matter connectivity. Compared with controls, the patients showed significantly decreased total connection strength. Furthermore, patients demonstrated significantly decreased connections within and between brain modules. Several local brain regions within association cortex exhibited reduced nodal centralities and abnormal participant coefficient or intra-module degree, some of which were correlated with illness duration and overall functional disability. In never-treated schizophrenia patients, networks showed a less effective organizational pattern of white matter pathways. White matter disconnectivity occurred not only within but also between multiple modules, shedding light on the deficits of anatomical network organization early in the course of schizophrenia.
| S-EPMC5814807 | biostudies-other
Project description:IntroductionDiffusion tensor imaging (DTI) studies in patients with schizophrenia have shown abnormalities in the microstructure of white matter tracts. Specifically, reduced fractional anisotropy (FA) has been described across multiple white matter tracts, in studies that have mainly included patients treated with antipsychotic medications.ObjectiveTo compare FA in antipsychotic-naïve patients experiencing a first episode of psychosis (FEP) to FA in healthy controls to demonstrate that the variance of FA can be grouped, in a coincidental manner, in four predetermined factors in accordance with a theoretical partition of the white matter tracts, using a principal components analysis (PCA).MethodsThirty-five antipsychotic-naïve FEP patients and 35 age- and gender-matched healthy controls underwent DTI at 3T. Analysis was performed using a tract-based spatial statistics (TBSS) method and exploratory PCA.ResultsDTI analysis showed extensive FA reduction in white matter tracts in FEP patients compared with the control group. The PCA grouped the white matter tracts into four factors explaining 66% of the total variance. Comparison of the FA values within each factor highlighted the differences between FEP patients and controls.DiscussionOur study confirms extensive white matter tracts anomalies in patients with schizophrenia, more specifically, in drug-naïve FEP patients. The results also indicate that a small number of white matter tracts share common FA anomalies that relate to deficit symptoms in FEP patients. Our study adds to a growing body of literature emphasizing the need for treatments targeting white matter function and structure in FEP patients.
| S-EPMC4339463 | biostudies-literature
Project description:BackgroundWhen psychosis develops in NMDA receptor (NMDAR) antibody encephalitis, it usually has an acute or subacute onset, and antipsychotic treatment may be ineffective and associated with adverse effects. Serum NMDAR antibodies have been reported in a minority of patients with first-episode psychosis (FEP), but their role in psychosis onset and response to antipsychotic treatment is unclear.MethodsSera from 387 patients with FEP (duration of psychosis <2 years, minimally or never treated with antipsychotics) undergoing initial treatment with amisulpride as part of the OPTiMiSE (Optimization of Treatment and Management of Schizophrenia in Europe) trial (ClinicalTrials.gov number NCT01248195) were tested for NMDAR IgG antibodies using a live cell-based assay. Symptom severity was assessed using the Positive and Negative Syndrome Scale and the Clinical Global Impressions Scale at baseline and again after 4 weeks of treatment with amisulpride.ResultsAt baseline, 15 patients were seropositive for NMDAR antibodies and 372 were seronegative. The seropositive patients had similar symptom profiles and demographic features to seronegative patients but a shorter duration of psychosis (median 1.5 vs. 4.0 months; p = .031). Eleven seropositive and 284 seronegative patients completed 4 weeks of amisulpride treatment: after treatment, there was no between-groups difference in improvement in Positive and Negative Syndrome Scale scores or in the frequency of adverse medication effects.ConclusionsThese data suggest that in FEP, NMDAR antibody seropositivity alone is not an indication for using immunotherapy instead of antipsychotic medications. Further studies are required to establish what proportion of patients with FEP who are NMDAR antibody seropositive have coexisting cerebrospinal fluid inflammatory changes or other paraclinical evidence suggestive of a likely benefit from immunotherapy.
| S-EPMC8191702 | biostudies-literature