Severity Of Neurological Soft Signs Research Articles

A preliminary study on similarities and dissimilarities of Neurological Soft Signs in schizophrenic and obsessive-compulsive disorders suggests a common maldevelopmental model.

Neurological Soft Signs (NSS) represent minor neurological signs related to non-specific cerebral alterations. They have been documented in many psychiatric disorders including schizophrenia (SCZ) and obsessive-compulsive disorder (OCD). Aim of this study was to determine and compare the incidence and severity of NSS in patients with SCZ, in patients with OCD, and healthy control subjects (HCs). Using the Neurological Evaluation Scale (NES), this study investigated NSS in 15 SCZ patients, 14 OCD patients, and 15 HCs. PANSS and Y-BOCS were used to evaluate clinical picture in both groups. Patients with SCZ showed significantly higher scores compared to HCs in the NES total and each of the three NES subscales (Integrative Sensory Function, Motor Coordination, and Sequencing of Complex Motor Acts). Patients with OCD also showed significantly higher scores compared to HCs in the NES total, Motor Coordination and Sequencing of Complex Motor Acts, but not in Integrative Sensory Function. No significant differences emerged in the NES total and the various subscales scores between the two patients' groups. Our results seem to confirm the presence of NSS in both SCZ and OCD. The different types of NSS presented by the two patients' groups versus HCs further supports the findings of widespread cerebral alterations in SCZ, on the other hand, with a preferential involvement of prefrontal and frontal cortex in OCD.

Investigation of structural brain correlates of neurological soft signs in individuals at ultra-high risk for psychosis.

Increased severity of neurological soft signs (NSS) in schizophrenia have been associated with abnormal brain morphology in cerebello-thalamo-cortical structures, but it is unclear whether similar structures underlie NSS prior to the onset of psychosis. The present study investigated the relationship between severity of NSS and grey matter volume (GMV) in individuals at ultra-high risk for psychosis (UHR) stratified for later conversion to psychosis. Structural T1-weighted MRI scans were obtained from 56 antipsychotic-naïve UHR individuals and 35 healthy controls (HC). The UHR individuals had follow-up data (mean follow-up: 5.2years) to ascertain clinical outcome. Using whole-brain voxel-based morphometry, the relationship between NSS and GMV at baseline was assessed in UHR, HC, as well as individuals who later transitioned (UHR-P, n = 25) and did not transition (UHR-NP, n = 31) to psychosis. NSS total and subscale scores except motor coordination were significantly higher in UHR compared to HC. Higher signs were also found in UHR-P, but not UHR-NP. Total NSS was not associated with GMV in the whole sample or in each group. However, in UHR-P individuals, greater deficits in sensory integration was associated with lower GMV in the left cerebellum, right insula, and right middle frontal gyrus. In conclusion, NSS are present in UHR individuals, particularly those who later transitioned to a psychotic disorder. While these signs show little overall variation with GMV, the association of sensory integration deficits with lower GMV in UHR-P suggests that certain brain areas may be implicated in the development of specific neurological abnormalities in the psychosis prodrome.

S187. EXPLORING NEURODEVELOPMENTAL AND FAMILIAL ORIGINS OF NEUROLOGICAL SOFT SIGNS IN SCHIZOPHRENIA

BackgroundThe neurodevelopmental hypothesis is the most widely regarded framework for understanding the development of schizophrenia. One of the most commonly cited pieces of evidence for this theory is the presence of neurological soft signs (NSS) in individuals prior to the onset of psychosis. Increased NSS is also reported in unaffected individuals with a family history of schizophrenia, suggesting that NSS may also have a familial component. Although much research has implicated reduced grey matter volume (GMV) in association with these signs, a subcomponent of volume, known as gyrification, has been poorly researched. Given that gyrification develops predominantly in prenatal life it may be particularly susceptible to a neurodevelopmental abnormality. The aims of this study were to investigate the neurodevelopmental and familial underpinnings of NSS in schizophrenia. Specifically, we examined the brain structural correlates, at both the level of GMV and gyrification, of NSS in individuals with schizophrenia, their unaffected relatives and healthy controls. We aimed to determine whether gyrification better predicted NSS severity than GMV, and whether the relationship between brain structure and NSS were present in a step-wise manner across the diagnostic groups.MethodsThe sample consisted of individuals with schizophrenia (N=66), their unaffected relatives (N=27) and healthy controls (N=53). NSS was assessed with the Neurological Evaluation Scale (NES), and GMV and gyrification were extracted from MRI using the FreeSurfer imaging suite. A series of analysis of covariance were used to compare NES scores and brain measures between the groups. Separate linear regression analyses were used to assess whether whole-brain GMV and gyrification predicted NES above a covariate-only model. Moderation analyses were used to assess whether the relationship between NES and brain structure were different between the diagnostic groups. Error control was achieved with a false discovery rate of 5%.ResultsNES was significantly higher in schizophrenia patients than relatives (p<.0001), who were in turn significantly higher than controls (p=.034). With the groups combined, lower GMV (p<.0001), as well as lower gyrification (p=.004), predicted higher NES above a covariate-only model. GMV predicted greater variance in NSS in comparison to gyrification, explaining an additional 20.3% of the variance in NES, in comparison to the additional 5.5% of variance in NES explained by gyrification. Diagnostic group moderated the association between GMV and NES (p=.019), but not between gyrification and NES (p=.245). Follow-up tests revealed that lower GMV was associated with higher NES in schizophrenia (t=-4.5, p<.0001) and relatives (t=-2.5, p=.015) but not controls (t=-1.9, p=.055).DiscussionOur findings indicate that NSS is heritable, being present in patients with established schizophrenia, and to a lesser extent, in unaffected relatives. Consistent with previous research, we revealed that GMV predicted NSS severity, suggesting that abnormalities in volume may underlie these signs. We additionally found that gyrification predicted, although to a lesser extent than volume, NSS severity, providing some support for schizophrenia being of possible neurodevelopmental origin. Evidence for an association between volume and NSS in relatives, whom are not confounded by illness-related factors such as medication and symptom severity, indicates a familial contribution to the neural underpinnings of NSS. Together, our study suggests that there may be various aetiological pathways underlying soft signs across the schizophrenia diathesis, some that may be of familial or neurodevelopmental origin.

Neurological soft signs in schizophrenia spectrum disorders are not confounded by current antipsychotic dosage

Neurological soft signs (NSS) have garnered increasing attention in psychiatric research on motor abnormalities in schizophrenia spectrum disorders (SSD). However, it remains unclear whether the assessment of NSS severity could have been confounded by current antipsychotic dosage. In this study, we recruited 105 patients with SSD that underwent a comprehensive motor assessment evaluating NSS and extrapyramidal motor symptoms (EPMS) by means of standardized instruments. Current antipsychotic dosage equivalence estimates were determined by the classical mean dose method (doses equivalent to 1 mg/d olanzapine). We used multiple regression analyses to describe the relationship between NSS, EPMS and antipsychotic medication. In line with our expectations, current antipsychotic dosage had no significant effects on NSS total score (p = 0.27), abnormal involuntary movements (p = 0.17), akathisia (p = 0.32) and parkinsonism (p = 0.26). Further, NSS total score had a significant effect on akathisia (p = 0.003) and parkinsonism (p = 0.0001, Bonferroni corr.), but only marginal effect on abnormal involuntary movements (p = 0.08). Our results support the notion that NSS are not significantly modulated by current antipsychotic dosage in SSD. The associations between NSS, akathisia and parkinsonism, as revealed by this study, support the genuine rather than medication-dependent origin of particular motor abnormalities in SSD.

Clinical evaluation of functional capacity in treatment resistant schizophrenia patients: Comparison and differences with non-resistant schizophrenia patients

Treatment resistant schizophrenia (TRS) is defined by poor or non-response to conventional antipsychotic agents. Functional capacity is defined as the baseline potential of a patient to function in the community, irrespective of actual achievements gained, and has never been studied in TRS. Here, we screened 182 patients with psychotic symptoms and separated them in TRS (n = 28) and non-TRS (n = 32) ones, to evaluate whether they exhibited differential extents and predictive clinical variables of functional capacity. Functional capacity was measured by the UCSD Performance-Based Skills Assessment (UPSA). Psychotic symptoms by PANSS, social functioning by PSP and SLOF, clinical severity of the illness, cognitive functioning, and neurological soft signs (NSS) were assessed. TRS patients had non-significant lower UPSA scores compared to non-TRS (t-test: p > 0.05). In TRS, UPSA score correlated with multiple clinical variables. The highest effect sizes were observed for PANSS negative score (r = −0.67, p < 0.005); SLOF Area1 score (r = 0.66, p < 0.005); NSS severity (r = −0.61, p < 0.005). Multivariate analysis showed that main predictors of UPSA score in TRS patients were PANSS negative score, education years, NSS, Problem Solving performances, and PSP score (F = 11.12, R2 = 0.75, p < 0.0005). These variables were not predictive of UPSA score in non-TRS patients. Hierarchical analysis found that variance in UPSA score mainly depended on negative symptoms, NSS, and problem solving (F = 15.21, R2 = 0.65, p < 0.0005). Path analysis individuated two separate paths to UPSA score. These results delineate a limited and independent group of candidate predictors to be putatively accounted for therapeutic interventions to improve functional capacity, and possibly social functioning, in TRS patients.

A qualititative study of neurological soft signs in obsessive compulsive disorder and effect of comorbid psychotic spectrum disorders and familiality on its expression in Indian population.

Obsessive Compulsive Disorder (OCD) is one of the most common psychiatric disorders, with lifetime prevalence of 2%-3% and is known to lie on a spectrum continuous with Schizophrenia and other affective psychosis. Neurological Soft Signs (NSS) have been reported to be higher in both Schizophrenia and affective psychosis, like bipolar disorder, and their first degree relatives but in OCD, the results have been inconsistent. It remains unclear if NSS occur at even higher rates in individuals who have a co-morbidity for OCD and either schizophrenia or bipolar disorder, as it might be expected if a broader neurodevelopmental hit underlies the pathophysiology of both OCD and these disorders. To assess and compare NSS in patients of OCD, OCD with Psychotic spectrum disorders (OCD-PSD), first degree relatives of OCD (FDR of OCD) and healthy controls. 90 subjects each were recruited in four groups- OCD, OCD-PSD, FDR of OCD and healthy controls, as per the pre-defined inclusion and exclusion criteria for each group. Diagnosis was made as per ICD-10 criteria and Cambridge Neurological Inventory, Part-2 was applied. This study found statistically significant difference between the severity of NSS among these groups. There was also a significant difference in presence of NSS in OCD with PSD group and OCD group. A greater abnormality of NSS in FDR of OCD compared to healthy controls was found. This difference in proportions and severity of NSS between groups points towards an underlying common neurobiological and etiopathological underpinning between OCD with and without comorbid PSDs and their first degree relatives.

Neurological soft signs in patients with schizophrenia: current knowledge and future perspectives in the post-genomics era

Neurological soft signs (NSS), minor and subtle neurological abnormalities in sensory integration and motor performance that are not part of a properly defined neurological syndrome, have been consistently observed in patients with schizophrenia. The prevalence estimates of NSS in patients with schizophrenia have been reported to be higher than in healthy subjects. Current evidence suggests that NSS are an integral part of the disease and cannot be fully explained by the exposure to antipsychotic medication, as they are already present in treatment-naive patients. NSS have been associated with cardinal features of the disorder such as cognitive impairment, psychopathological severity, or functional outcome. The increased prevalence of NSS and/or related motor precursors has been described at different stages of development (infancy, childhood, adolescence) in those subjects who later developed schizophrenia. Evidence from family and twin studies indicates that genetic factors play an important role in the emergence of NSS, and some authors have already suggested that such neurological anomalies are suitable endophenotypes for schizophrenia. Some genetic association studies based on a candidate gene approach have already reported the association of genetic variants with the severity of NSS. This non-systematic review describes the potential relevance of NSS 1) in the understanding of schizophrenia as a neurodevelopmental disorder, 2) as outcome predictors, 3) as biological markers during several stages of development, and 4) as a candidate (endo)phenotype for genetic analyses. Likewise, the possibilities afforded by the advances in high-throughput techniques in genomic analysis are also discussed. Keywords: genome-wide association studies; motor function; sensory integration; endophenotype (Published: 8 July 2016) Citation: Translational Developmental Psychiatry 2016, 4 : 30071 - http://dx.doi.org/10.3402/tdp.v4.30071

Neurological soft signs in adolescents with borderline personality traits

Objective. This study investigated the prevalence and severity of neurological soft signs (NSS), and their relationships with borderline personality (BP) traits in adolescents. Methods. Eighty-nine adolescents with BP traits (BP-trait group), and 89 adolescents without traits of any personality disorder (control group), were recruited in China. BP traits were diagnosed by the BPD subscale of the Personality Diagnostic Questionnaire for the DSM-IV (PDQ-4+). The soft sign subscales of the Cambridge Neurological Inventory were administered to all participants. The group differences in prevalence of soft signs and in NSS scores were analyzed, as well as the associations between the NSS scale and borderline personality traits. Results. Five soft signs were significantly more frequent in adolescents with BP traits. A total of 59.6% of adolescents with BP traits exhibited at least 1 NSS, whereas only 34.8% of adolescents without BP traits did (p < 0.01). A total of 42.7% of adolescents in the BP-trait group exhibited at least 2 NSS, while only 16.9% of adolescents without BP traits did (p < 0.001). Moreover, adolescents with BP traits showed more sensory integration, disinhibition, total neurological soft signs, left-side soft signs, and right-side soft signs, than adolescents without BP traits. Sensory integration and disinhibition were positively associated with BP traits. Conclusion. These findings suggest that adolescents with BP traits may have a nonfocal abnormality of the central nervous system.

Correlation of neurological soft signs and neurocognitive performance in first episode psychosis

Neurological soft signs and neurocognitive impairments are commonly observed in first episode psychosis but the correlation of these factors remains controversial. Here, we evaluated 30 patients with remitted first episode psychosis and 30 healthy controls for the presence and severity of neurological soft signs (using the Neurological Evaluation Scale - NES) and for neurocognitive impairments (using seven subtests of the Cambridge Neuropsychological Test Automated Battery - CANTAB). NES score was higher in patients compared to controls. Neurocognitive impairment was evident in patients in the following domains: working memory, spatial recognition memory, attention set shifting, planning and inhibition. The NES revealed significant correlations with spatial working memory performance and Intra-Extra Dimensional Set Shifting (as a component of executive function). These correlations were observed both in patients and in controls. Planning and inhibition showed correlation with the total NES score and the sequencing of complex motor acts in both groups. In addition, spatial span and spatial recognition memory showed significant correlation with total NES score and the sequencing of complex motor acts in controls. The correlation between sequencing of complex motor acts and specific domains of neurocognitive tasks suggests that similar neuroanatomical substrates might be implicated in these processes.

Neurological Soft Signs and Brainstem Morphology in First-Episode Schizophrenia

Background: Minor motor and sensory deficits or neurological soft signs (NSS) have frequently been reported in patients with schizophrenia at any stage of their illness. NSS have been demonstrated to correlate with neuroanatomical abnormalities in various brain regions. Despite its important role in the integration and coordination of automatic motor actions, the brainstem has so far rather been ignored in previous neuroimaging studies on NSS in schizophrenia. Method: We investigated 21 right-handed first-episode schizophrenia patients using high-resolution magnetic resonance imaging at 3 T. The severity of NSS was measured with the Heidelberg Scale. Associations between NSS and both brainstem volume and shape changes were examined. Results: Higher NSS scores were significantly associated with structural alterations in the brainstem. According to volume measurements higher NSS scores correlated with global changes of the brainstem. Using shape analyses these associations referred to regionally specific morphometric alterations predominantly in the midbrain and pons. Conclusion: The findings suggest that brainstem morphometric alterations are associated with the severity of NSS in patients with first-episode schizophrenia. They further indicate the involvement of the brainstem in the pathogenesis of schizophrenia.

Less Cognitive and Neurological Deficits in Schizophrenia Patients Carrying Risk Variant in ZNF804A

Background: The rs1344706 single nucleotide polymorphism in the ZNF804A gene is a common variant with strong evidence for association with schizophrenia. Recent studies show an association of rs1344706 with cognitive functioning, and there is some evidence suggesting that the risk allele may increase susceptibility for a subtype of schizophrenia with relatively spared cognition. Methods: We tested the effect of rs1344706 genotype in 89 schizophrenia patients on 3 basic cognitive domains (working memory, processing speed and attention) shown to be severely impaired in schizophrenia. Also we investigated the effect of rs1344706 on the severity of neurological soft signs, subtle impairments in motor and sensory functions highly frequent in schizophrenia patients. Neurological soft signs and cognitive deficits are central features of schizophrenia and are tightly linked with clinical, social and functional outcome. Results: Our results show an association of higher rs1344706 risk allele load with improved performance on processing speed and with fewer neurological soft signs. Conclusions: Together with other studies, our findings suggest that ZNF804A is associated with a subtype of schizophrenia with better cognitive and neurological functioning. Discovery of the specific pathways through which ZNF804A is exerting this effect may lead to better prevention, diagnosis and treatment for a specific group of schizophrenia patients.

Neurological soft signs in obsessive–compulsive disorder: The effect of co-morbid psychosis and evidence for familiality

Patients with obsessive-compulsive disorder (OCD) have increased rates of neurological soft signs (NSS) when compared to healthy controls. However, previous findings have been confounded by the presence of co-morbidity with disorders themselves associated with increased NSS, such as schizophrenia. Moreover, it remains unclear whether NSS in OCD reflect a vulnerability to this disorder. This study aimed to examine: 1) the severity of NSS in patients with OCD alone, in patients with OCD and co-morbid psychosis (schizophrenia or bipolar disorders), and in healthy controls; and b) whether unaffected first-degree relatives of patients with OCD also demonstrate a higher prevalence rate of NSS than healthy controls. NSS were assessed with the Cambridge Neurological Inventory (CNI) in 100 patients with OCD, 38 patients with OCD and psychosis (22 with bipolar disorders and 16 with schizophrenia), and 101 healthy controls. Forty-seven unaffected first-degree relatives of patients with OCD only were also administered the CNI. Patients with OCD showed significantly higher scores in motor coordination and total NSS than controls, and patients with OCD co-morbid with psychosis also showed significantly higher scores in motor coordination and total NSS than controls. Although there were no differences in NSS between patients with OCD only and OCD and psychosis as a whole, patients with OCD co-morbid with schizophrenia showed significantly higher scores in motor coordination than patients with OCD, patients with OCD and bipolar disorder, and healthy controls. Unaffected first-degree relatives only showed a higher prevalence rate than healthy controls in specific motor coordination signs, such as Opposition and Extinction. These findings suggest that patients with OCD exhibit more NSS than healthy controls, and that motor coordination signs may be even more extensive when OCD is co-morbid with psychosis. Some of these abnormalities may be indicative of a vulnerability to these disorders, as indicated by their presence in un-affected first-degree relatives.

The reduction of superoxide dismutase activity is associated with the severity of neurological soft signs in patients with schizophrenia

This study aimed to explore the relationship between antioxidant enzyme activities and neurological soft signs (NSS) in a sample of patients with schizophrenia. Sixty clinically stable patients with schizophrenia treated mostly by first-generation antipsychotics and 30 matched healthy controls were recruited. NSS were assessed in two groups by a standardized neurological examination (Krebs et al., 2000). The red blood cell (RBC) antioxidant activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were measured by spectrophotometry. RBC activities of all enzymes studied: SOD, GSH-Px and CAT, were significantly lower in the patients compared to control group. All NSS scores were significantly higher in the patients compared to healthy controls' scores. In the patients, a negative correlation was found between RBC SOD activity and NSS total score and motor coordination and motor integration sub-scores. The association between low SOD activity as a marker of oxidative stress and NSS in schizophrenic patients suggests a common pathological process of these abnormalities.

Brain morphology and neurological soft signs in adolescents with first-episode psychosis

Adolescents with first-episode psychosis have increased severity of neurological soft signs when compared with controls, but it is unclear whether increased severity of neurological soft signs is an expression of specific structural brain deficits. To examine whether increased severity of neurological soft signs was associated with decreased brain volumes in adolescents with first-episode psychosis. Brain scans were obtained for 70 adolescents (less than 18 years of age) with first-episode psychosis (duration of positive symptoms less than 6 months). Volumes were assessed using voxel-based morphometry and through segmentation of anatomical structures. Increased severity of sensory integration neurological soft signs correlated with smaller right and left thalamus volume, whereas increased severity of sequencing of complex motor acts neurological soft signs correlated with smaller right caudate volume. Neurological soft signs may be an easy-to-assess marker of region-specific structural brain deficits in adolescents with first-episode psychosis.

Neurological outcomes in children with and without amalgam-related mercury exposure: Seven years of longitudinal observations in a randomized trial

Although large-scale, randomized trials involving children have been completed and their results demonstrate an absence of neurobehavioral effects from clinical exposure to mercury amalgam, neurological findings from such studies have not been reported. The authors conducted a randomized, prospective trial examining the safety of dental amalgam in which 507 children aged 8 through 12 years were assigned to treatment with either amalgam or resin-based composite. During seven years of follow-up, the authors performed annual clinical neurological examinations, including an evaluation of neurological hard signs (NHSs), presence of tremor and neurological soft signs (NSSs). The authors found no significant differences between treatment groups in any of the neurological measures. Groups did not differ with respect to the presence or absence of NHSs or tremor, nor the presence or absence or severity of NSSs at any point. As expected, NSS severity scores diminished with increasing age. Even at the levels of amalgam exposure in this study (a mean of 7.7-10.7 amalgam surfaces per subject across the seven years of follow-up), the authors conclude that exposure to mercury from dental amalgam does not adversely affect neurological status. The current evidence is that potential neurobehavioral or neurological effects from dental amalgam mercury exposure in children are inconsequential.

Neurological soft signs and their relationship to 1-year outcome in first-episode schizophrenia

Objectives To examine the relationship between the severity of neurological soft signs at onset and at the 1-year follow-up of patients with schizophrenia, and to investigate temporal stability of neurological soft signs within 1 year from the onset of the first episode schizophrenia. Methods The study included 92 first-episode male schizophrenic patients. Neurological soft signs were assessed on the Neurological Evaluation Scale (NES) during index hospitalization and at a 1-year follow-up. The patients were divided into remitters and non-remitters according to their psychiatric status assessed at the 1-year follow-up, using the Positive and Negative Syndrome Scale (PANSS). Results A trend for a lower score for the NES item “others” in late remitters versus non-remitters at baseline was found during index hospitalization. At the 1-year follow-up, the overall severity of the neurological soft signs was statistically significantly higher in non-remitters than in remitters. Within 1 year after index hospitalization, a significant reduction of neurological soft signs, with the exception of sensory integration, occurred in remitters. Within 1 year after index hospitalization, the non-remitters reported a significant reduction of the overall NES score. Conclusion These findings in a population of patients with first episode schizophrenia are in accord with the findings of previous studies which found an association between neurological soft signs, treatment response and outcome. This association may characterize a subgroup of patients with a poor course of illness and outcome. Neurological soft signs might be regarded as one of the indicators of treatment outcome in patients suffering from their first episode of schizophrenia.

Deficit of Executive Functions in Schizophrenia: Relationship to Neurological Soft Signs and Psychopathology

Cognitive deficits and neurological soft signs (NSS) have frequently been reported in schizophrenic patients and they both appear related to prominent negative symptoms. The aim of the present study was to examine the relationship between deficit of executive functioning, assessed by the Wisconsin Card Sorting Test (WCST), NSS and psychopathological dimensions of schizophrenia in order to address the issue of whether a typology of schizophrenic patients may be identifiable by clinical, neurological and neuropsychological features. A sample of 26 male schizophrenic patients was divided, on the basis of the performance on the WCST, into two subgroups (‘good performers’ and ‘poor performers’) that were compared for the prevalence and severity of NSS, assessed by the Neurological Evaluation Scale (NES), and for the psychopathological features, assessed using the Positive and Negative Syndrome Scale (PANSS). To test for between-group differences, ANOVA was conducted. The ‘poor performers’ group showed greater severity of NSS: significant differences emerged for the NES total score and for the ‘sequencing of complex motor acts’ score. However, no significant differences between the groups emerged for any PANSS score. These findings seem to indicate that a common neurobiological abnormality could underlie cognitive deficits, especially concerning executive functioning, and subtle neurological abnormalities often present in schizophrenia, but they appear to deny that such dysfunctional correlates of schizophrenia are related to a prominent negative symptomatology.