Course of neurological soft signs in first-episode schizophrenia: Relationship with negative symptoms and cognitive performances.
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ABSTRACT:
SUBMITTER: Chan RC
PROVIDER: S-EPMC4459190 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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Project description:Neurological soft signs (NSS) are often found in patients with schizophrenia. A wealth of neuroimaging studies have reported that NSS are related to disturbed cortical-subcortical-cerebellar circuitry in schizophrenia. However, the association between NSS and brain network abnormalities in patients with schizophrenia remains unclear. In this study, the graph theoretical approach was used to analyze brain network characteristics based on structural magnetic resonance imaging (MRI) data. NSS were assessed using the Heidelberg scale. We found that there was no significant difference in global network properties between individuals with high and low levels of NSS. Regional network analysis showed that NSS were associated with betweenness centrality involving the inferior orbital frontal cortex, the middle temporal cortex, the hippocampus, the supramarginal cortex, the amygdala, and the cerebellum. Global network analysis also demonstrated that NSS were associated with the distribution of network hubs involving the superior medial frontal cortex, the superior and middle temporal cortices, the postcentral cortex, the amygdala, and the cerebellum. Our findings suggest that NSS are associated with alterations in topological attributes of brain networks corresponding to the cortical-subcortical-cerebellum circuit in patients with schizophrenia, which may provide a new perspective for elucidating the neural basis of NSS in schizophrenia.
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Project description:Neurological soft signs (NSSs), minor neurological abnormalities, have been implicated as risk factors for poor cognitive performance in small-scale studies. Here we investigate the associations between NSSs and multiple domains of cognitive performance in a large, population-based cohort and evaluate sex differences in these associations. We analyzed data from 35,710 seven-year-old children in the Collaborative Perinatal Project to study the association between the number of NSSs and cognitive test scores using multiple linear regression models adjusting for risk factors for brain injury and aberrant neurodevelopment. NSSs were associated with lower scores on all domains of cognitive performance. Each additional soft sign was associated with lower full-scale IQ (b = -4.83, 95% CI [-5.06, -4.60]), performance IQ (b = -4.28, 95% CI [-4.54, -4.02]), and verbal IQ scores (b = -4.53, 95% CI [-4.76, -4.30]), as well as arithmetic (b = -4.06, 95% CI [-4.26, -3.85]), spelling (b = -3.53, 95% CI [-3.75, -3.30]), and reading (b = -4.00, 95% CI [-4.26, -3.75]) scores on the Wide Range Achievement Test (WRAT). Only one sex difference was observed: The association between NSS and the WRAT spelling test was somewhat stronger in girls (b = -4.01, 95% CI [-4.26, -3.36]) than in boys (b = -3.53, 95% CI [-3.75, -3.30]). There is an association between NSSs and poor cognitive performance that is not attributable to established risk factors for brain injury and aberrant neurodevelopment. Further research is needed to investigate the mechanisms underlying this association and to determine if interventions targeting NSS in children might have beneficial effects on neurocognitive development. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
| S-EPMC6202138 | biostudies-literature
Project description:The present study examined different types of neurological signs in patients with first-episode schizophrenia and their relationships with neurocognitive functions. Both cross-sectional and longitudinal designs were adopted with the use of the abridged Cambridge Neurological Inventory which comprises items capturing motor coordination, sensory integration and disinhibition. A total of 157 patients with first-episode schizophrenia were assessed at baseline and 101 of them were re-assessed at six-month interval. A structural equation model (SEM) with invariance model across time was used for data analysis. The model fitted well with the data at baseline assessment, X^2(21) = 21.78, p = 0.413, NFI = 0.95, NNFI = 1.00, CFI = 1.00, IFI = 1.00, RMSEA = 0.015. Subsequent SEM analysis with invariance model at six-month interval also demonstrated the same stable pattern across time and showed strong measurement invariance and structure invariance across time. Our findings suggest that neurological signs capture more or less the same construct captured by conventional neurocognitive tests in patients with schizophrenia. The measurement and structure of these relationships appear to be stable over time.
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Project description:Neurological soft signs (NSS) are related to grey matter and functional brain abnormalities in schizophrenia. Studies in healthy subjects suggest, that NSS are also linked to white matter. However, the association between NSS and white matter abnormalities in schizophrenia remains to be elucidated. The present study investigated, if NSS are related to white matter alterations in patients with schizophrenia. The total sample included 42 healthy controls and 41 patients with schizophrenia. We used the Neurological Evaluation Scale (NES), and we acquired diffusion weighted magnetic resonance imaging to assess white matter on a voxel-wise between subject statistic. In patients with schizophrenia, linear associations between NES with fractional anisotropy (FA), radial, axial, and mean diffusivity were analyzed with tract-based spatial statistics while controlling for age, medication dose, the severity of the disease, and motion. The main pattern of results in patients showed a positive association of NES with all diffusion measures except FA in important motor pathways: the corticospinal tract, internal capsule, superior longitudinal fascicle, thalamocortical radiations and corpus callosum. In addition, exploratory tractography analysis revealed an association of the right aslant with NES in patients. These results suggest that specific white matter alterations, that is, increased diffusivity might contribute to NSS in patients with schizophrenia.
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Project description:Cerebellar dysfunction is associated with neurological soft signs (NSS), which is a promising endophenotype for schizophrenia spectrum disorders. However, the relationship between cerebellar-cerebral resting-state functional connectivity (rsFC) and NSS is largely unexplored. Moreover, both NSS and cerebellar-cerebral rsFC have been found to be correlated with negative symptoms of schizophrenia. Here, we investigated the correlations between NSS and cerebellar-cerebral rsFC, explored their relationship with negative symptoms in a main dataset, and validated the significant findings in a replication dataset. Both datasets comprised schizophrenia patients and healthy controls. In schizophrenia patients, we found positive correlations between NSS and rsFC of the cerebellum with the inferior frontal gyrus and the precuneus, and negative correlations between NSS and rsFC of the cerebellum with the inferior temporal gyrus. In healthy controls, NSS scores were positively correlated with rsFC of the cerebellum with the superior frontal gyrus and negatively correlated with rsFC between the cerebellum and the middle occipital gyrus. Cerebellar-prefrontal rsFC was also positively correlated with negative symptoms in schizophrenia patients. These findings were validated in the replication dataset. Our results suggest that the uncoupling of rsFC between the cerebellum and the cerebral cortex may underlie the expression of NSS in schizophrenia. NSS-related cerebellar-prefrontal rsFC may be a potential neural pathway for possible neural modulation to alleviate negative symptoms.
| S-EPMC8379549 | biostudies-literature
Project description:Neurological soft signs (NSSs) bear the promise for early detection of schizophrenia spectrum disorders. Nonetheless, the sensitivity and specificity of NSSs in the psychosis continuum remains a topic of controversy. It is also unknown how NSSs reveal neurodevelopmental abnormality in schizophrenia. We investigated the effect sizes of NSSs in differentiating individuals with schizophrenia spectrum disorders from individuals with other psychiatric conditions and from covariate-matched healthy subjects. We also investigated the partitioned age-related variations of NSSs in both schizophrenia and healthy individuals. NSSs were assessed by the abridged version of the Cambridge Neurological Inventory (CNI) in 3105 participants, consisting of healthy individuals (n=1577), unaffected first-degree relatives of schizophrenia patients (n= 155), individuals with schizotypal personality disorder (n= 256), schizophrenia patients (n= 738), and other psychiatric patients (n= 379). Exact matching and propensity score matching procedures were performed to control for covariates. Multiple regression was used to partition age-related variations. Individuals along the schizophrenia continuum showed elevated levels of NSSs, with moderate effect sizes, in contrast to other psychiatric patients who had minimal NSSs, as well as matched healthy controls. Furthermore, the age-and-NSS relationship in schizophrenia patients was represented by a flat but overall elevated pattern, in contrast to a U-shaped pattern in healthy individuals. In sum, NSSs capture a moderate portion of psychosis proneness with reasonable specificity. Lifespan profiling reveals an abnormal developmental trajectory of NSSs in schizophrenia patients, which supports the endophenotype hypothesis of NSSs by associating it with the neurodevelopmental model of schizophrenia.
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Project description:Schizophrenia is associated with widespread cortical and subcortical abnormalities. Studies examining cognitive deficits in schizophrenia have historically focused on cortical deficits; however, many subcortical areas also support cognition. We sought to determine whether deficits in subcortical gray matter are linked to neurocognitive dysfunction in patients with first-episode schizophrenia. This study included 170 patients with first-episode schizophrenia and 88 healthy controls. Clinical symptoms, neurocognitive function, and structural images were assessed. Subcortical volumes were recorded. Patients had significant deficits in all cognitive domains, including processing speed, attention, memory, executive function and social cognition. Patients also demonstrated significantly smaller volumes in the amygdala, hippocampus, thalamus, and total cortical gray matter than did controls after Bonferroni correction for multiple comparisons. Reasoning/problem solving was significantly and positively correlated with the volume of the amygdala and nucleus accumbens in patients. Positive symptoms of psychosis were positively correlated with the volume of the amygdala and nucleus accumbens. In addition, the dose of antipsychotic medication was positively correlated with the volume of the amygdala, nucleus accumbens, caudate, putamen, and pallidum. In conclusion, schizophrenia is associated with profound cognitive deficits. Our findings suggest that subcortical structures contribute to specific domains of cognitive dysfunction in first-episode schizophrenia.
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Project description:Extrapyramidal (EP) symptoms such as tremor, rigidity, and bradykinesia are common side effects of most antipsychotics, and may associate with impaired performance in neurocognitive testing. We studied EP symptoms in first-episode psychosis (FEP; n = 113). Cognitive testing and EP symptoms (three items of the Simpson-Angus Scale) were assessed at baseline and follow-up (mean follow-up time 12 months). Mild EP symptoms were present at treatment onset in 40% of the participants. EP symptoms were related with lower performance in neurocognitive testing at baseline and at follow-up, especially among those with nonaffective psychotic disorder, and especially in tasks requiring speed of processing. No associations between EP symptoms and social cognition were detected. In linear regression models, when positive and negative symptom levels and chlorpromazine equivalents were accounted for, baseline EP symptoms were associated with worse baseline global neurocognition and visuomotor performance. Baseline EP symptoms also longitudinally predicted global, verbal, and visuomotor cognition. However, there were no cross-sectional associations between EP symptoms and cognitive performance at follow-up. In sum, we found both cross-sectional and longitudinal associations between EP symptoms and neurocognitive task performance in the early course of psychosis. Those without EP symptoms at the start of treatment had higher baseline and follow-up neurocognitive performance. Even mild EP symptoms may represent early markers of long-term neurocognitive impairment.
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Project description:Subtle abnormalities in sensory integration, motor coordination and sequencing of complex motor acts or neurological soft signs (NSS) are characteristic phenomena in patients with schizophrenia at any stage of the illness. Previous MRI studies in schizophrenia found NSS to be associated with cortical, thalamic and cerebellar changes. Since these studies mainly focused on first-episode or recent onset schizophrenia, the cerebral correlates of NSS in chronic schizophrenia remained rather unclear. 49 middle-aged patients with chronic schizophrenia with a mean duration of illness of 20.3 ± 14.0 years and 29 healthy subjects matched for age and sex were included. NSS were examined on the Heidelberg Scale and correlated to grey matter (GM) by using whole brain high resolution magnetic resonance imaging (3 Tesla) with SPM12/CAT12 analyses. As expected, NSS in patients were significantly (p?0.001) elevated in contrast to healthy controls, a finding, which not only applied to NSS total score, but also to the respective subscales "motor coordination", "sensory integration", "complex motor tasks", "right/left and spatial orientation" and "hard signs". Within the patient group NSS total scores were significantly correlated to reduced GM in right lingual gyrus, left parahippocampal gyrus, left superior temporal gyrus, left thalamus (medial dorsal nucleus) and left posterior lobe of the cerebellum (declive). Respective negative associations could also be revealed for the subscales "motor coordination", "complex motor tasks" and "right/left and spatial orientation". These findings remained significant after FWE-correction for multiple comparisons and were confirmed when years of education, chlorpromazine-equivalents or variables indicating the severity of psychopathology were introduced as additional covariates. According to our results lingual, parahippocampal, superior temporal, inferior and middle frontal gyri, thalamus and cerebellum have to be considered as important sites of NSS in chronic schizophrenia. That these findings only applied for patients but not healthy controls may indicate a different pathogenesis of NSS.
| S-EPMC7176089 | biostudies-literature
Project description:The heritability of schizophrenia and most personality traits has been well established, but the role of personality in susceptibility to schizophrenia remains uncertain. The aim of this study was to test for an association between personality traits and Neurological Soft Signs (NSS), a well-known biological marker of schizophrenia, in non-psychotic relatives of patients with schizophrenia. For this purpose, we evaluated the NSS scale and personality measured by the Temperament and Character inventory (TCI-R) in three groups of subjects: 29 patients with schizophrenia, 24 unaffected relatives and 37 controls. The results showed that patients with schizophrenia were more asocial (higher harm avoidance and lower reward dependence), more perseverative (higher persistence), and more schizotypal (lower self-directedness and cooperativeness, higher self-transcendence). The unaffected relatives showed higher harm avoidance, lower self-directedness and cooperativeness than the healthy controls. Higher NSS scores and sub-scores were found in patients and non-psychotic relatives compared with the controls. Among all the patients, total NSS scores were positively correlated with harm avoidance but negatively correlated with novelty seeking and persistence. Total NSS were also correlated with low scores on self-directedness and cooperativeness, which are indicators of personality disorder. Our results show that susceptibility to NSS and to schizophrenia are both related to individual differences in the temperament and character features in non-psychotic relatives of patients with schizophrenia. High harm avoidance, low persistence, low self-directedness and low cooperativeness contribute to both the risk of NSS and schizophrenia. These findings highlight the value of using both assessments to study high risk populations.
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