Motor abnormalities are frequently observed in schizophrenia and structural alterations of the motor system have been reported. The association of aberrant motor network function, however, has not ...been tested. We hypothesized that abnormal functional connectivity would be related to the degree of motor abnormalities in schizophrenia. In 90 subjects (46 patients) we obtained resting stated functional magnetic resonance imaging (fMRI) for 8 minutes 40 seconds at 3T. Participants further completed a motor battery on the scanning day. Regions of interest (ROI) were cortical motor areas, basal ganglia, thalamus and motor cerebellum. We computed ROI-to-ROI functional connectivity. Principal component analyses of motor behavioral data produced 4 factors (primary motor, catatonia and dyskinesia, coordination, and spontaneous motor activity). Motor factors were correlated with connectivity values. Schizophrenia was characterized by hyperconnectivity in 3 main areas: motor cortices to thalamus, motor cortices to cerebellum, and prefrontal cortex to the subthalamic nucleus. In patients, thalamocortical hyperconnectivity was linked to catatonia and dyskinesia, whereas aberrant connectivity between rostral anterior cingulate and caudate was linked to the primary motor factor. Likewise, connectivity between motor cortex and cerebellum correlated with spontaneous motor activity. Therefore, altered functional connectivity suggests a specific intrinsic and tonic neural abnormality in the motor system in schizophrenia. Furthermore, altered neural activity at rest was linked to motor abnormalities on the behavioral level. Thus, aberrant resting state connectivity may indicate a system out of balance, which produces characteristic behavioral alterations.
Several prominent theories of schizophrenia suggest that structural white matter pathologies may follow a developmental, maturational, and/or degenerative process. However, a lack of lifespan studies ...has precluded verification of these theories. Here, we analyze the largest sample of carefully harmonized diffusion MRI data to comprehensively characterize age-related white matter trajectories, as measured by fractional anisotropy (FA), across the course of schizophrenia. Our analysis comprises diffusion scans of 600 schizophrenia patients and 492 healthy controls at different illness stages and ages (14-65 years), which were gathered from 13 sites. We determined the pattern of age-related FA changes by cross-sectionally assessing the timing of the structural neuropathology associated with schizophrenia. Quadratic curves were used to model between-group FA differences across whole-brain white matter and fiber tracts at each age; fiber tracts were then clustered according to both the effect-sizes and pattern of lifespan white matter FA differences. In whole-brain white matter, FA was significantly lower across the lifespan (up to 7%; p < 0.0033) and reached peak maturation younger in patients (27 years) compared to controls (33 years). Additionally, three distinct patterns of neuropathology emerged when investigating white matter fiber tracts in patients: (1) developmental abnormalities in limbic fibers, (2) accelerated aging and abnormal maturation in long-range association fibers, (3) severe developmental abnormalities and accelerated aging in callosal fibers. Our findings strongly suggest that white matter in schizophrenia is affected across entire stages of the disease. Perhaps most strikingly, we show that white matter changes in schizophrenia involve dynamic interactions between neuropathological processes in a tract-specific manner.
Schizophrenia patients are severely impaired in nonverbal communication, including social perception and gesture production. However, the impact of nonverbal social perception on gestural behavior ...remains unknown, as is the contribution of negative symptoms, working memory, and abnormal motor behavior. Thus, the study tested whether poor nonverbal social perception was related to impaired gesture performance, gestural knowledge, or motor abnormalities. Forty-six patients with schizophrenia (80%), schizophreniform (15%), or schizoaffective disorder (5%) and 44 healthy controls matched for age, gender, and education were included. Participants completed 4 tasks on nonverbal communication including nonverbal social perception, gesture performance, gesture recognition, and tool use. In addition, they underwent comprehensive clinical and motor assessments. Patients presented impaired nonverbal communication in all tasks compared with controls. Furthermore, in contrast to controls, performance in patients was highly correlated between tasks, not explained by supramodal cognitive deficits such as working memory. Schizophrenia patients with impaired gesture performance also demonstrated poor nonverbal social perception, gestural knowledge, and tool use. Importantly, motor/frontal abnormalities negatively mediated the strong association between nonverbal social perception and gesture performance. The factors negative symptoms and antipsychotic dosage were unrelated to the nonverbal tasks. The study confirmed a generalized nonverbal communication deficit in schizophrenia. Specifically, the findings suggested that nonverbal social perception in schizophrenia has a relevant impact on gestural impairment beyond the negative influence of motor/frontal abnormalities.
Schizophrenia is characterized by social interaction deficits contributing to poor functional outcome. Hand gesture use is particularly impaired, linked to frontal lobe dysfunction and frontal grey ...matter deficits. The functional neural correlates of impaired gesturing are currently unclear. We therefore investigated aberrant brain activity during impaired gesturing in schizophrenia. We included 22 patients with schizophrenia and 25 healthy control participants matched for age, gender, and education level. We obtained functional magnetic resonance imaging data using an event-related paradigm to assess brain activation during gesture planning and execution. Group differences in whole brain effects were calculated using factorial designs. Gesture ratings were performed by a single rater, blind to diagnoses and clinical presentation. During gesture planning and execution both groups activated brain areas of the praxis network. However, patients had reduced dorsolateral prefrontal cortex (DLPFC) and increased inferior parietal lobe (IPL) activity. Performance accuracy was associated with IPL activity in patients. Furthermore, patients activated temporal poles, amygdala and hippocampus during gesture planning, which was associated with delusion severity. Finally, patients demonstrated increased dorsomedial prefrontal cortex activity during planning of novel gestures. We demonstrate less prefrontal, but more IPL and limbic activity during gesturing in schizophrenia. IPL activity was associated with performance accuracy, whereas limbic activity was linked to delusion severity. These findings may reflect impaired social action planning and a limbic interference with gestures in schizophrenia contributing to poor gesture performance and consequently poor social functioning in schizophrenia.
Schizophrenia patients present with a variety of impaired nonverbal communication skills. Performance of hand gestures is frequently impaired and associated with ratings of motor abnormalities. ...However, the impact of motor abnormalities to gesture performance remains unclear. To test the association between quantitative measures of motor behavior and qualitative ratings of gesture performance, we quantified movement parameters semi-automatically in videotaped recordings of gesture assessment. Thirty-one patients with schizophrenia (77.4%), schizophreniform (19.4%) or schizoaffective disorder (3.2%) and 32 healthy controls matched for age, gender and education underwent clinical assessment. Performance of the test of upper limb apraxia (TULIA) was video-taped in all subjects. The videos were analyzed with motion energy analysis software (MEA) to determine motion and time parameters.
Patients and controls differed significantly in quantitative gesture performance: patients required more movement and more time to complete the tasks. Differences increased in patients with qualitatively impaired gesture production ratings (p<0.01). Group differences were most pronounced in the pantomime domain, when gestures are performed following verbal instruction. In patients, ratings of motor abnormalities correlated with duration of movement, while behavioral disorganization correlated with the amount of movements during gesture performance.
Disorder related motor symptoms, aberrant action observation, planning and monitoring as well as internal clock abnormalities may explain the poor performance of hand gestures in schizophrenia. Quantitative video analysis offers a unique possibility to analyze movement patterns as a direct functional output of the motor system. In the future, it may assist monitoring, staging and prognosis in schizophrenia.
Up to 50% of patients with schizophrenia are suffering from motor abnormalities, which may contribute to decreased quality of life, impaired work capacity, and a reduced life expectancy by ...10–20 years. However, the effect of motor abnormalities on social and global functioning, as well as, functional capacity is not clear. We hypothesized, that the presence of motor abnormalities is associated with poorer functional outcomes in patients with schizophrenia.
We collected data on 5 different motor abnormalities in 156 patients suffering from schizophrenia spectrum disorders: parkinsonism, catatonia, dyskinesia, neurological soft signs and psychomotor slowing (PS). Additionally, we used three different scales to evaluate the functional outcomes in these patients: the Global Assessment of Functioning (GAF) and the Social and Occupational Functioning Assessment Scale (SOFAS) which use clinicians' judgment; and one using a performance-based measure of functional capacity, the brief version of the UCSD Performance-based Skills Assessment (UPSA-B).
Our analysis demonstrated that patients with catatonia (all F > 4.5; p < 0.035) and parkinsonism (all F > 4.9; p < 0.027) scored lower on GAF and SOFAS compared to patients without catatonia and parkinsonism. In contrast, no significant difference on functional outcomes between patients with dyskinesia versus without dyskinesia exist in our study. Furthermore, there are statistically significant negative correlations for parkinsonism and PS with GAF, SOFAS and UPSA-B (all tau are at least −0.152, p-value <0.036). We also found significant negative correlations between catatonia and both GAF & SOFAS (all tau are at least −0.203, p-value<0.001) and between NES and SOFAS (tau = −0.137, p-value = 0.033).
Here, we showed that four of the most common motor abnormalities observed in schizophrenia were associated with at least one of the patients' functional outcomes. The stronger the motor impairment was the worse the global and social functioning. Future studies need to test, whether amelioration of motor abnormalities is linked to improved community functioning.
•Motor abnormalities are one of the core symptoms in schizophrenia.•Different motor abnormalities distinctly impact functional outcomes.•The stronger the motor impairment is, the worse the global and social functioning.•Therapies targeting motor abnormalities' amelioration may improve functioning.
Psychiatric disorders share an excess of seasonal birth in winter and spring, suggesting an increase of neurodevelopmental risks. Evidence suggests season of birth can serve as a proxy of harmful ...environmental factors. Given that prenatal exposure of these factors may trigger pathologic processes in the neurodevelopment, they may consequently lead to brain volume alterations. Here we tested the effects of season of birth on gray matter volume in a transdiagnostic sample of patients with schizophrenia and depression compared to healthy controls (
n
= 192). We found a significant effect of season of birth on gray matter volume with reduced right hippocampal volume in summer-born compared to winter-born patients with depression. In addition, the volume of the right hippocampus was reduced independent from season of birth in schizophrenia. Our results support the potential impact of season of birth on hippocampal volume in depression.
White matter (WM) abnormalities are repeatedly demonstrated across the schizophrenia time-course. However, our understanding of how demographic and clinical variables interact, influence, or are ...dependent on WM pathologies is limited. The most well-known barriers to progress are heterogeneous findings due to small sample sizes and the confounding influence of age on WM. The present study leverages access to the harmonized diffusion magnetic-resonance-imaging data and standardized clinical data from 13 international sites (597 schizophrenia patients (SCZ)). Fractional anisotropy (FA) values for all major WM structures in patients were predicted based on FA models estimated from a healthy population (n = 492). We utilized the deviations between predicted and real FA values to answer three essential questions. (1) "Which clinical variables explain WM abnormalities?". (2) "Does the degree of WM abnormalities predict symptom severity?". (3) "Does sex influence any of those relationships?". Regression and mediator analyses revealed that a longer duration-of-illness is associated with more severe WM abnormalities in several tracts. In addition, they demonstrated that a higher antipsychotic medication dose is related to more severe corpus callosum abnormalities. A structural equation model revealed that patients with more WM abnormalities display higher symptom severity. Last, the results exhibited sex-specificity. Males showed a stronger association between duration-of-illness and WM abnormalities. Females presented a stronger association between WM abnormalities and symptom severity, with IQ impacting this relationship. Our findings provide clear evidence for the interaction of demographic, clinical, and behavioral variables with WM pathology in SCZ. Our results also point to the need for longitudinal studies, directly investigating the casualty and sex-specificity of these relationships, as well as the impact of cognitive resiliency on structure-function relationships.
Abstract The reward system in schizophrenia has been linked to the emergence of delusions on the one hand and to negative symptoms such as affective flattening on the other hand. Previous Diffusion ...Tensor Imaging (DTI) studies reported white matter microstructure alterations of regions related to the reward system. The present study aimed at extending these findings by specifically investigating connection pathways of the reward system in schizophrenia. Therefore, 24 patients with schizophrenia and 22 healthy controls matched for age and gender underwent DTI-scans. Using a probabilistic fiber tracking approach we bilaterally extracted pathways connecting the ventral tegmental area (VTA) with the nucleus accumbens (NAcc), the medial and lateral orbitofrontal cortices (mOFC, lOFC), the dorsolateral prefrontal cortex (dlPFC) and the amygdala; as well as pathways connecting NAcc with mOFC, lOFC, dlPFC and amygdala resulting in a total of 18 connections. Probability indices forming part of a bundle of interest (PIBI) were compared between groups using independent t-tests. In 6 connection pathways PIBI-values were increased in schizophrenia. In 3 of these pathways the spatial extension of connection pathways was decreased. In schizophrenia patients, there was a negative correlation of PIBI-values and PANSS negative scores in the left VTA–amygdala and in the left NAcc–mOFC connection. A sum score of delusions and hallucinations correlated positively with PIBI-values of the left amygdala–NAcc connection. Structural organization of specific segments of white matter pathways of the reward system in schizophrenia may contribute to the emergence of delusions and negative symptoms in schizophrenia.
The aim of our study was to investigate whether self-reported feeling of loneliness (FoL) and COVID-19-specific health anxiety were associated with the presence of depressive symptoms during the ...first coronavirus disease 2019 (COVID-19) wave. Questionnaires of 603 persons of the Swiss Multiple Sclerosis Registry (SMSR) were cross-sectionally analyzed using descriptive and multivariable regression methods. The survey response rate was 63.9%. Depressive symptoms were assessed by the Beck Depression Inventory-Fast Screen (BDI-FS). COVID-19-specific health anxiety and FoL were measured using two 5-item Likert scaled pertinent questions. High scoring FoL (2.52, 95% confidence interval (CI) (2.06-2.98)) and/or COVID-19 specific health anxiety (1.36, 95% CI (0.87-1.85)) were significantly associated with depressive symptoms. Further stratification analysis showed that the impact of FoL on depressive symptoms affected all age groups. However, it was more pronounced in younger PwMS, whereas an impact of COVID-19 specific health anxiety on depressive symptoms was particularly observed in middle-aged PwMS. FoL and COVID-19-specific health anxiety were age-dependently associated with depressive symptoms during the first COVID-19 wave in Switzerland. Our findings could guide physicians, health authorities, and self-help groups to better accompany PwMS in times of public health crises.
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