Neurological Soft Signs Scores Research Articles

Neurological soft signs and olfactory dysfunction in patients with borderline personality disorder

BackgroundBorderline personality disorder (BPD) is a serious disorder with a lifetime prevalence of 2.7–5.9% and is thought to correlate with altered neuroplasticity. The aim of the present study is to investigate possible associations of BPD (−severity) and alterations in neurological soft signs (NSS) and olfactory function. MethodsFor the monocentric observational study, 39 female subjects with a BPD diagnosis and 19 female healthy control subjects were recruited. The groups were matched by age. Olfactory functions were examined using Sniffin’ Sticks. NSS were assessed by a standardized test with 50 items. ResultsBPD subjects have higher NSS scores in group comparison. By contrast, there are no alterations in the total score of olfactory function, while the BPD subjects scored higher in smell identification. Within the BPD group, the total NSS score was discovered to have a negative correlation with olfactory function. BPD subjects taking antipsychotics show more NSS than those without. We found no significant influence of posttraumatic stress disorder on the NSS or olfactory function. The BPD-severity correlates with NSS. LimitationsDue to the cross-sectional design, we did not have a follow up examination. The sample size was small, and all patients had psychiatric comorbidities. Additionally, we did not perform MRI to connect our findings with possible structural abnormalities. ConclusionsOur study confirmed altered NSS in BPD patients, whereas no impairment in the olfactory function was found. Further research is required to establish NSS and smell tests as clinical screening tools in BPD patients and to uncover the disorder's impact on neuroplasticity.

Neurological soft signs as trait markers of a subset of patients with obsessive-compulsive disorder with low insight and altered cognitive abilities

Neurological soft signs (NSS) are subtle motor control impairments that include involuntary movements and abnormalities of motor coordination, sensory integration and lateralization. They engage different brain networks, including the prefrontal networks that support the higher cognitive functions that are dysfunctional in obsessive-compulsive disorder (OCD). This study investigated the relationships between the presence of NSS and patients' severity of OCD symptoms, insight, and treatment resistance in a sample of 63 patients. Treatment-resistance was assessed considering all the treatments the patients received during the course of their disease. The four dimensions of OCD defined in the dimensional obsessive-compulsive scale were considered. Links between the patients’ cognitive abilities and NSS were assessed using tests targeting specifically the core components of executive functions.As expected, OCD patients displayed more NSS than individually matched control participants. In OCD patients, high NSS scores were associated with poor insight and lower cognitive abilities. Multiple regression analysis identified worse visuospatial working memory, attentional control, and verbal fluency as predictive factors of high NSS scores among cognitive functions. Unexpectedly, the patients displaying symptoms in the contamination/washing dimension displayed less NSS than the other patients. In contrast, neither the severity of OCD symptoms nor long-range treatment resistance was significantly related to patients’ NSS scores. Altogether, our findings suggest that high NSS scores may be a trait marker of a subset of OCD patients with low insight and particularly altered cognitive abilities who would not express the contamination/washing dimension of the pathology.

Predicting the Outcome of First Episode Psychosis Subjects by Assessing Dorsolateral Prefrontal Cortex Volume

Aim: Dorsolateral prefrontal cortex (DLPFC), Neurological Soft Signs (NSS) and Cognitive impairment have been described as predictors of outcome of First Episode Psychosis (FEP), therefore we aimed to find the predictors of clinical, social and functional outcome variables in a cohort of first episode non affective psychotic subjects. Subjects and Methods: A prospective follow up study was conducted from August 2018 to August 2020 in a tertiary care hospital of South India. A semi-structured questionnaire was given to all subjects for socio-demographic details. All subjects were assessed with Heidelberg scale, Bender Gestalt Test (BGT) and underwent MRI Brain 3D volumetric scan to examine NSS, cognitive impairment, and DLPFC volume at baseline respectively. Brief Psychiatric Rating Scale (BPRS) and Social and Occupational Functioning Assessment Scale scales (SOFAS) were administered at baseline, 1 month and at three month follow up. At 3 months, clinical and socio-functional outcome was defined by BPRS scores and SOFAS scores. Pearson’s correlation was found between DLPFC volume of all subjects, BPRS, BGT scores at baseline with BPRS and SOFAS at 3 months. To test the statistical significance of the comparison of mean values of all continuous clinical and demographic parameters between two groups of BPRS and SOFAS, Mann Whitney U test was used. Results: Smaller DLPFC volume predicted clinical, socio-functional outcome significantly. A significant moderate correlation was found between NSS and BPRS scores at baseline. Conclusion: Baseline right DLPFC volume can be an important predictor of clinical and socio-functional outcome in FEP.

A Study of Neurological Soft Signs and Cognition in Schizophrenia.

Neurological soft signs (NSS) are delicate neurological abnormalities that comprise deficits in motor coordination, problems with the sequencing of complex motor acts, and sensory integration difficulties. These are nonspecific with no specific localization in the brain. NSS are found in many patients with Schizophrenia. Cognitive dysfunctions are also present in more than two-thirds of patients with Schizophrenia. This study aims at assessing the NSS and its association with cognitive impairment in patients with Schizophrenia. A total of 100 Schizophrenia patients were included in the study. The Heidelberg scale was used for assessing the NSS. The Montreal Cognitive Assessment Scale(MoCA) for cognitive impairment, the Positive and Negative Syndrome Scale(PANSS) for Schizophrenia, and the Brief Psychiatric Rating Scale (BPRS) were used to assess the severity. Statistical analysis was performed by Pearson's Chi-square test, Kruskal-Wallis test, Wilcoxon rank testsand Spearman rank correlation along with mean and standard deviation. NSS were present in 68% (N=68) of the patients with motor coordination being maximally affected. Cognitive impairment was found in 73% (N=73) of patients with a MoCA score <26. Patients with predominant negative symptoms had higher NSS scores and lower MoCA scores. A "statistically significant" correlation was observed between cognitive impairment and NSS. Most patients with NSS and impaired cognition were in the "markedly ill" category of BPRS. A significant association was observed between cognitive deficits, negative symptoms, and NSS in Schizophrenia.NSS and cognitive dysfunctions are integral parts of Schizophrenia symptomdomains and need to be assessed as the negative symptoms and severity of illness are associated with NSS, especially problems with motor coordination and cognitive dysfunctions.

Neurological Soft Signs in Schizophrenia, a Picture of the Knowledge in the Last Decade: A Scoping Review.

(1) Background: Neurological Soft Signs (NSS) are subtle neurological abnormalities that are more common in schizophrenia patients than in healthy individuals and have been regularly observed in neuroleptic-naive first-episode patients, supporting the hypothesis that they are an intrinsic component of schizophrenia. (2) Methods: a review of articles published in the last ten years (from January 2013 to January 2023) was carried out on articles published in ScienceDirect and PubMed, by following the PRISMA Statement extension for scoping reviews (PRISMA-ScR), which evaluated the impact of NSS in correlation with the symptomatology, neuroleptic treatment, and the cerebral structural changes of patients with schizophrenia. (3) Results: thirty articles were included, among them twelve included MRI structural evaluation and four studies with a longitudinal design. (4) Conclusions: interest in researching NSS has increased in recent years, but questions remain about their origin and relationship to schizophrenia symptoms, thus this study aims to fill in information gaps in the hope that future research will help provide individualized treatment. It is suggested that NSS in schizophrenia might have an inherited genetic relationship pattern, thus being in line with a trait viewpoint. Most of the research revealed that schizophrenia patients had higher NSS scores than healthy controls, however, they were rather similar to their first-degree relatives, thus, also arguing in favor of a trait perspective. The greatest improvement in scores is seen in those with a remitting course, as shown by declining NSS ratings concurrent with symptomatology.

Neurological soft signs and brain morphology in people living with HIV

Neurological soft signs (NSS) are a common feature of severe psychiatric disorders such as schizophrenia but are also prevalent in organic brain diseases like HIV-associated neurocognitive disorder (HAND) or Alzheimer’s disease. While distinct associations between NSS, neurocognition, and cerebral regions were demonstrated in schizophrenia, these associations still have to be elucidated in HIV. Therefore, we investigated 36 persons with HIV of whom 16 were neurocognitively healthy and 20 were diagnosed with HAND. NSS were assessed using the Heidelberg scale. NSS scores were correlated with gray matter (GM) using whole brain voxel-based morphometry. Results showed significantly elevated NSS in the HAND group when compared to the neurocognitively healthy with respect to NSS total score and the subscores “orientation” and “complex motor tasks”. While the two groups showed only minor, non-significant GM differences, higher NSS scores (subscales “motor coordination”, “orientation”) were significantly correlated with GM reduction in the right insula and cerebellum (FWE-corrected). Our results corroborate elevated NSS in HIV+ patients with HAND in contrast to cognitively unimpaired patients. In addition, cerebral correlates of NSS with GM reductions in insula and cerebellum were revealed. Taken together, NSS in this patient group could be considered a marker of cerebral damage and neurocognitive deficits.

Dyslexia: Links with schizotypy and neurological soft signs.

Abnormalities in language processing, psychological distress, and subtle neurodevelopmental features called neurological soft signs (NSS) are expressed by people with dyslexia and those scoring highly on schizotypy. We investigated whether the expression of NSS, distress, and schizotypy predicted dyslexia status. Participants (N=96, 48 dyslexic) selected to be age and sex matched, completed the Schizotypal Personality Questionnaire, General Health Questionnaire, Neurological Evaluation Scale, and the National Adult Reading Test (NART; a measure of verbal intelligence). Dyslexia status was predicted by higher total NSS and disorganized schizotypy scores in the absence of NART. However, even with the inclusion of NART, disorganized schizotypy remained a significant predictor. The findings suggest that disorganized features of schizotypy could be a significant factor for those with dyslexia. Conversely, more attention needs to be given to developmental language disorders in those who score highly on schizotypy.

Neurological Soft Signs (NSS) in Census-Based, Decade-Adjusted Healthy Adults, 20 to >70 Years of Age.

Neurological soft signs (NSS) represent minor neurological features and have been widely studied in psychiatric disease. The assessment is easily performed. Quantity and quality may provide useful information concerning the disease course. Mostly, NSS scores differ significantly between patients and controls. However, literature does not give reference values. In this pilot study, we recruited 120 healthy women and men to build a cross-sectional, census-based sample of healthy individuals, aged 20 to >70 years, subdivided in 10-year blocks for a close approach to the human lifeline. Testing for NSS and neurocognitive functioning was performed following the exclusion of mental and severe physical illness. NSS scores increased significantly between ages 50+ and 60+, which was primarily accountable to motor signs. Gender and cognitive functioning were not related to changes of scores. Although the number of individuals is small, study results may lay a foundation for further validation of NSS in healthy individuals.

Neurological Soft Signs Are Associated With Altered Cerebellar-Cerebral Functional Connectivity in Schizophrenia.

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.

Neurological soft signs correlation with symptom severity in borderline personality disorder

BackgroundBorderline personality disorder (BPD) is a severe psychiatric disorder with multiple psychopathological domains; so studying the correlation of clinical or behavioral data with underlying structural and functional neurological findings in BPD is the focus of interest in recent years.The aim of our study was to compare the presence of neurological soft signs (NSS) in patients with borderline personality disorder with their presence in normal controls, and to correlate the severity of different symptoms of BPD with the presence of NSS through a case-control study which was conducted on 30 patients and 30 matching controls recruited from Al Kasr Al Ainy Hospital, Cairo University, Egypt. All subjects were assessed by the Borderline Personality Questionnaire, the Barratt Impulsivity Scale-11, the Brief Non-Suicidal Self-Injury Assessment tool, and the Cambridge Neurological Inventory.ResultsThe BPD group had significantly higher total NSS scores, primitive reflexes subscale score, and sensory integration subscale scores. There was also a positive correlation between NSS and overall severity of borderline symptoms.ConclusionsThe increased rates of NSS were associated with specific clinical symptoms in BPD including suicidality, self-harm, emptiness, and quasi-psychosis. Impulsivity was found to have the highest correlation with NSS.

Moving forward: distinct sensorimotor abnormalities predict clinical outcome after 6 months in patients with schizophrenia

Despite substantial efforts in the last decades, objective measures that can predict clinical outcome in patients with schizophrenia (SZ) after an acute psychotic episode are still lacking. Here, we introduced a comprehensive assessment of sensorimotor function to predict mid-term clinical outcome following an acute psychotic episode. This naturalistic follow-up of 43 patients with DSM-IV-TR diagnosis of SZ examined sensorimotor abnormalities (i.e. Neurological Soft Signs (NSS), parkinsonism, akathisia, catatonia and acute dyskinesia), psychopathology, cognition and psychosocial functioning using well-established instruments. A collection of statistical methods was used to examine the relationship between sensorimotor domain, psychopathology, cognition and psychosocial functioning. We also tested the clinical feasibility of this relationship when predicting clinical outcome after an acute psychotic episode. Longitudinal data were collected on 43 individuals after a follow-up period of >6 months. At follow-up, patients showed significantly reduced general symptom severity, as well as decreased levels of NSS, parkinsonism and catatonia. Further, NSS scores at baseline predicted PANSS negative scores and cognitive functioning at baseline. Finally, NSS scores at baseline predicted symptom change (reduction of PANSS positive and negative scores) at follow-up. In conclusion, our results suggest that NSS are significant predictors of poor clinical outcome in SZ at baseline and >6 months after an acute psychotic episode. These findings propose sensorimotor domain as state biomarker of SZ and support its predictive power with respect to treatment outcome.

P.213 Specific polygenic risk scores discriminate asymptomatic at-risk individuals according to their brain amyloid load

Despite substantial efforts in the last decades, objective measures that can predict clinical outcome in patients with schizophrenia (SZ) after an acute psychotic episode are still lacking. Here, we introduced a comprehensive assessment of sensorimotor function to predict mid-term clinical outcome following an acute psychotic episode. This naturalistic follow-up of 43 patients with DSM-IV-TR diagnosis of SZ examined sensorimotor abnormalities (i.e. Neurological Soft Signs (NSS), parkinsonism, akathisia, catatonia and acute dyskinesia), psychopathology, cognition and psychosocial functioning using well-established instruments. A collection of statistical methods was used to examine the relationship between sensorimotor domain, psychopathology, cognition and psychosocial functioning. We also tested the clinical feasibility of this relationship when predicting clinical outcome after an acute psychotic episode. Longitudinal data were collected on 43 individuals after a follow-up period of >6 months. At follow-up, patients showed significantly reduced general symptom severity, as well as decreased levels of NSS, parkinsonism and catatonia. Further, NSS scores at baseline predicted PANSS negative scores and cognitive functioning at baseline. Finally, NSS scores at baseline predicted symptom change (reduction of PANSS positive and negative scores) at follow-up. In conclusion, our results suggest that NSS are significant predictors of poor clinical outcome in SZ at baseline and >6 months after an acute psychotic episode. These findings propose sensorimotor domain as state biomarker of SZ and support its predictive power with respect to treatment outcome.

Associations between brain structural networks and neurological soft signs in healthy adults

Neurological soft signs (NSS), as minor neurological deficits, have been identified in several psychiatric disorders, especially in schizophrenia. However, it's unclear how the neuropathological processes of the disease affect NSS related brain morphological changes and whether it is confounded by the use of medication. As NSS also exist in healthy people, the potential confounding effects of psychopathology or medication will be excluded if NSS are investigated in healthy people. Therefore, we applied a novel multivariate approach, source-based morphometry (SBM), to study structural networks in relation to NSS in healthy adults based on structural magnetic resonance imaging (MRI) data. The Heidelberg Scale was applied to evaluate NSS. Using SBM, we constructed structural networks and investigated their associations with NSS in healthy adults. Six grey matter (GM) structural networks were identified. Sensory integration subscores were associated with the cerebellar component and the cortico-basal ganglia-thalamic component. Motor coordination subscores and total NSS scores were associated with the sensorimotor component. The present findings indicated that structural network abnormalities in cerebellar, subcortical and cortical sensorimotor areas contribute to NSS performance in healthy adults.

Neurological soft signs (NSS) and cognitive impairment in chronic schizophrenia

Recent studies indicate that neurological soft signs (NSS) in schizophrenia are associated with generalized cognitive impairments rather than changes in specific neuropsychological domains. However, the majority of studies solely included first-episode patients or patients with a remitting course and did not consider age, course, education or severity of global cognitive deficits as potential confounding variables. Therefore, we examined NSS with respect to cognitive deficits in chronic schizophrenia, i.e. patients who are particularly vulnerable to both, NSS and cognitive impairments.Eighty patients with chronic schizophrenia (43.36 ± 15a) and 60 healthy controls (47.52 ± 14.8a) matched for age, sex and years of education were examined on the Heidelberg NSS scale and a broad neuropsychological battery including short term, working, logical and autobiographic memory (AM), theory of mind (ToM), psychomotor speed and cognitive flexibility.When contrasted with the controls, patients showed significantly higher NSS scores and impairments in all neuropsychological domains but short-term memory. NSS were significantly associated with all neuropsychological domains considered but short-term memory and semantic AM. Except for episodic AM (which was significantly correlated with NSS in patients only) these correlations applied to both groups and were confirmed when age, years of education and severity of global cognitive deficits (Mini Mental State Examination) were controlled for.Results demonstrate that NSS reflect a rather wide range of cognitive impairments in schizophrenia, which also involves episodic AM and ToM. These associations were not accounted for by age, education or severity of global cognitive deficits and facilitate the clinical usage of NSS as a screening instrument.

Neurological soft signs and grey matter abnormalities in individuals with ultra-high risk for psychosis.

Neurological soft signs (NSSs), conventionally defined as subtle neurological abnormalities, are frequently found in individuals with schizophrenia. Many neuroimaging studies have also reported that NSSs are associated with grey matter changes in patients with schizophrenia at different stages of the illness. However, these findings may be confounded by the effect of antipsychotic medications, chronicity, and duration of untreated psychosis. Examining NSSs in individuals with ultra-high risk (UHR) for psychosis may help to identify the neuroanatomical substrates of NSSs related to the illness itself and to avoid these potential confounding effects. A sample of 21 individuals with UHR were included in the present study. NSSs were rated using the abridged version of the Cambridge Neurological Inventory. Grey matter volume was assessed using optimized voxel-based morphometry on images acquired by a high-resolution 3-T magnetic resonance imaging scanner. We found that higher NSS scores in individuals with UHR were associated with decreased grey matter volume at the superior and medial frontal cortex, the rectal cortex, the pre- and post-central cortex, the insula, the caudate, and the cerebellum. Our results suggest that these brain structural characteristics may represent the neuroanatomical substrate of NSSs in individuals with UHR. These findings contribute to the understanding of the intrinsic features of psychosis associated with NSSs and may provide insights into pre-schizophrenia pathophysiology.

Neurological soft signs as a marker of cognitive impairment severity in people living with HIV

HIV-associated neurocognitive disorders (HAND) include asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND) and HIV-associated dementia. Early recognition of HAND is crucial, and usually requires thorough neuropsychological testing. Neurological soft signs (NSS), i.e. minor motor and sensory changes, a common feature in severe psychiatric disorders, may facilitate early diagnosis. NSS were examined using the Heidelberg NSS Scale in 18 patients with ANI, 21 with MND, 28 HIV positive patients without HAND, and 39 healthy controls matched for age, gender, and education. The highest NSS scores were obtained in the MND patients (13.3 ± 10.0, p < 0.0001) followed by those with ANI (11.7 ± 10.6), the HIV positive subjects without neurocognitive deficits (8.0 ± 4.1) and the healthy controls (3.8 ± 3.2). This result was confirmed when age and years of school education were entered as covariates. No significant correlations between NSS and CD4 counts or any other clinical variables were found among the HIV positive groups. Our results demonstrate that NSS are frequently found in both ANI and MND but not HIV positive patients without neurocognitive deficits. NSS may facilitate the screening of HIV positive patients for ANI and MND as an easier and less expensive clinical tool.

F125. POOR OUTCOME SCHIZOPHRENIA (KRAEPELINIAN SUB-TYPE): SOCIAL COGNITIVE AND NEURODEVELOPMENTAL MARKERS

BackgroundPoor outcome schizophrenia represents a public health challenge and it asks questions about neurodevelopmental mechanisms by its own. The kraepelinian schizophrenia sub-type, defined by Keefe’s criteria (1987), refers to a very poor prognosis sub-group (severe dysfunction in self-care) on the basis of the longitudinal course of the illness. Studies on kraepelinian sub-group show differences with good outcome patients regarding pre-morbid functioning, negative and disorganized symptoms, impaired performance on specific social cognitive and motor deficits (visual-motor processing, abstraction/flexibility, fine motor dexterity) (Albus and al., 1996; Bralet and al., 2006). Neurological soft signs (NSS) refer to subtle neurological abnormalities comprising deficits in sensory integration, motor coordination and sequencing of complex motor acts. Previous studies showed that NSS scores are correlated to schizophrenia, specifically among patients with poor premorbid functioning and with severe negative and disorganization symptoms. NSS could be a neurodevelopmental marker interesting to detect patients with a risk of poor prognosis. Deficits in theory of mind is correlated with disorganization and poor prognosis. The aim of our study was to explore the association between NSS, Theory of Mind and kraepelinian sub-type in order to understand better the etiopathogenic mechanisms underlying the kraepelinian sub-type.MethodsIn 2016, we recruited 2 samples of 25 schizophrenic patients, kraepelinians and no-kraepelinians, matched on sex, ages (+/- 5 years) and duration of illness (+/- 5 years) from the psychiatric departments in Picardie area (France), according to DSM-IV-TR criteria and using Keefe’s criteria. Several socio-demographical, pharmacological, clinical, cognitive and NNS (with the 3 subscores, sensory integration, motor integration and motor coordination) (Krebs and al., 2000) were collected for each patient. To compare the 2 sub-groups we used bi-variate analysis and multivariate regression analysis (p< 0,05)ResultsResults showed a worse significant NSS score among kraepelinian patients: total score, sensory integration, motor integration, motor coordination, p< 0,0001; there was no link with treatment (equ mg/day chlorpromazine). As well kraepelinians show worse significantly performance at the eye gaze test p<0,001. Multivariate analysis showed that kraepelinian sub-type is more explained significantly by eyes-test, motor integration and disorganization dimensionDiscussionPoor prognosis schizophrenia refers to specific and complex neurodevelopmental mechanisms which could be markers of a poor outcome. We must confirm these results in a larger prospective cohort from UHR and first episode assessing some specific neurodevelopmental markers using NSS and cognitive assessment. As well some specific biological markers and genes implicating in neurodevelopment and glutamatergic system could be studied in these patients. Focusing on these specific markers could contribute to define innovating combinating therapeutic strategies (pharmacological, cognitive remediation and social skills) to avoid poor prognosis.

Neurological Soft Signs and Psychopathology in Chronic Schizophrenia: A Cross-Sectional Study in Three Age Groups.

As established in a wealth of studies subtle motor and sensory neurological abnormalities or neurological soft signs (NSS) are frequently found in patients with schizophrenia at any stage of their illness. However, the potential impact of chronicity and age on NSS was scarcely investigated. Therefore, we assessed NSS in 90 patients with subchronic (n = 22) or chronic (n = 68) schizophrenia and in 60 healthy controls who were assigned to three age groups (18–29, 30–49, and +50 years). NSS were measured on the Heidelberg Scale, psychopathological symptoms including apathy were rated on established instruments. As demonstrated by analysis of variance, NSS scores in patients were significantly (p < 0.05) increased relative to healthy controls. Significant age effects arose in all NSS subscores, with older subjects scoring well above the younger ones. These age effects were more pronounced in patients than controls, indicating that NSS in chronic schizophrenia exceed age-associated changes. Moreover, the NSS scores in patients were significantly associated with duration of illness, thought disturbance, positive symptoms, and apathy. These results were confirmed after age/duration of illness and years of education were partialed out and via regression analyses. Our findings conform to the hypothesis that NSS are associated with chronicity of the disorder as indicated by the correlations of NSS with both, duration of illness and apathy. The correlations between NSS and positive symptoms/thought disturbance correspond to the fluctuation of positive symptoms during the course of the disorder. The significantly more pronounced age effects on NSS in patients may either point to ongoing cerebral changes or to a greater susceptibility of patients toward physiological age effects, which may be mediated among other factors by a lower cognitive reserve.

Default Mode Network Aberrant Connectivity Associated with Neurological Soft Signs in Schizophrenia Patients and Unaffected Relatives.

Brain connectivity and neurological soft signs (NSS) are reportedly abnormal in schizophrenia and unaffected relatives, suggesting they might be useful neurobiological markers of the illness. NSS are discrete sensorimotor impairments thought to correspond to deviant brain development. Although NSS support the hypothesis that schizophrenia involves disruption in functional circuits involving several hetero modal association areas, little is known about the relationship between NSS and brain connectivity. We explored functional connectivity abnormalities of the default mode network (DMN) related to NSS in schizophrenia. A cross-sectional study was performed with 27 patients diagnosed with schizophrenia, 23 unaffected relatives who were unrelated to the schizophrenia subjects included in the study, and 35 healthy controls. Subjects underwent magnetic resonance imaging scans including a functional resting-state acquisition and NSS evaluation. Seed-to-voxel and independent component analyses were used to study brain connectivity. NSS scores were significantly different between groups, ranging from a higher to lower scores for patients, unaffected relatives, and healthy controls, respectively (analysis of variance effect of group F = 56.51, p < 0.001). The connectivity analysis revealed significant hyperconnectivity in the fusiform gyrus, insular and dorsolateral prefrontal cortices, inferior and middle frontal gyri, middle and superior temporal gyri, and posterior cingulate cortex [minimum p-family wise error (FWE) < 0.05 for all clusters] in patients with schizophrenia as compared with in controls. Also, unaffected relatives showed hyperconnectivity in relation to controls in the supramarginal association and dorsal posterior cingulate cortices (p-FWE < 0.05 for all clusters) in patients with schizophrenia as compared with in controls. Also, unaffected relatives showed hyperconnectivity in relation to controls in the supramarginal association and dorsal posterior cingulate cortices (p-FWE = 0.001) and in the anterior prefrontal cortex (42 voxels, p-FWE = 0.047). A negative correlation was found between left caudate connectivity and NSS [p-FWE = 0.044, cluster size (k) = 110 voxels]. These findings support the theory of widespread abnormal connectivity in schizophrenia, reinforcing DMN hyperconnectivity and NSS as neurobiological markers of schizophrenia. The results also indicate the caudate nucleus as the gateway to the motor consequences of abnormal DMN connectivity.

Neurological Soft Signs in Schizophrenia: An Update on the State- versus Trait-Perspective.

Neurological soft signs (NSS) represent minor neurological signs, which indicate non-specific cerebral dysfunction. In schizophrenia, their presence has been documented extensively across all stages of the disease. Until recently, NSS were considered an endophenotype or a trait phenomenon. During the past years, however, researchers report fluctuations of the NSS scores. To further clarify the question whether NSS exhibit state or trait components or both, studies that have investigated NSS longitudinally were reviewed. Studies which have assessed NSS longitudinally in adults suffering from schizophrenia, were searched for. The time frame was January 1966 to June 2017. Studies on teenagers were excluded because of interferences between brain maturation and pathology. Twenty-nine follow-up studies were identified. They included patients during different stages of their illness and mainly used established instruments for NSS assessment. Patients with a first episode or a remitting course predominantly show a decrease of NSS over time, whereas a worsening of NSS can be found in the chronically ill. It was shown that change of NSS total scores over time is predominantly caused by motor system subscales and to a lesser extent by sensory integration scales. With respect to medication, the majority of studies agree on a relationship between medication response and improvement of NSS while the type of antipsychotic does not seem to play a major role. Moreover, where information on side-effects is given, it does not favor a strong relationship with NSS. However, NSS seem to correlate with negative and cognitive symptoms. Studies manifest a conformity regarding the presence of NSS in schizophrenia patients on the one hand. On the other hand, fluctuations of NSS scores have been widely described in subgroups. Taken together results strongly support a state-trait dichotomy of NSS. Thus, the usage of NSS as an endophenotype has to be called into question.