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.

Patterns of co-altered brain structure and function underlying neurological soft signs in schizophrenia spectrum disorders.

Neurological soft signs (NSS) comprise a broad range of subtle neurological deficits and are considered to represent external markers of sensorimotor dysfunction frequently found in mental disorders of presumed neurodevelopmental origin. Although NSS frequently occur in schizophrenia spectrum disorders (SSD), specific patterns of co-altered brain structure and function underlying NSS in SSD have not been investigated so far. It is unclear whether gray matter volume (GMV) alterations or aberrant brain activity or a combination of both, are associated with NSS in SSD. Here, 37 right-handed SSD patients and 37 matched healthy controls underwent motor assessment and magnetic resonance imaging (MRI) at 3 T. NSS were examined on the Heidelberg NSS scale. We used a multivariate data fusion technique for multimodal MRI data-multiset canonical correlation and joint independent component analysis (mCCA + jICA)-to investigate co-altered patterns of GMV and intrinsic neural fluctuations (INF) in SSD patients exhibiting NSS. The mCCA + jICA model indicated two joint group-discriminating components (temporoparietal/cortical sensorimotor and frontocerebellar/frontoparietal networks) and one modality-specific group-discriminating component (p < .05, FDR corrected). NSS motor score was associated with joint frontocerebellar/frontoparietal networks in SSD patients. This study highlights complex neural pathomechanisms underlying NSS in SSD suggesting aberrant structure and function, predominantly in cortical and cerebellar systems that critically subserve sensorimotor dynamics and psychomotor organization.

Differential contributions of brainstem structures to neurological soft signs in first- and multiple-episode schizophrenia spectrum disorders.

Neurological soft signs (NSS) are frequently found in patients with schizophrenia spectrum disorders (SSD) at any stage of the disease. Brainstem structures are crucial for motor control, integration of sensory input and coordination of automatic motor actions. It is unclear whether disease duration has an impact on NSS/brainstem volume relationships. We tested the hypothesis that volumes of brainstem structures differ between first-episode psychosis (FEP) and multiple-episodes psychosis (MEP) patients with SSD, and that alterations of these structures are associated with NSS. T1-weighted structural MRI data at 3 T were obtained from 92 right-handed SSD patients (27 FEP and 65 MEP). FreeSurfer vers. 6.0 was used for segmentation of brainstem structures including the medulla oblongata, pons, superior cerebellar pedunculus (SCP), and midbrain. Multiple regression analyses were used to describe the relationship between brainstem structures and distinct NSS subdomains. In FEP, pons volume had a significant effect on NSS total score (p = 0.001, Bonferroni corr.). Further, medulla oblongata (p = 0.001, Bonferroni corr.) and pons (p = 0.001, Bonferroni corr.) volumes had a significant effect on NSS motor coordination score. In MEP, significant associations between brainstem structures and NSS levels were not found. The present data support the notion that brainstem structures play an important role in the expression of NSS in SSD individuals with FEP, in contrast to individuals with MEP. Our study also emphasizes the need of better characterizing episode-specific brainstem correlates of NSS in SSD.

Cortical Contributions to Distinct Symptom Dimensions of Catatonia.

Catatonia is a central aspect of schizophrenia spectrum disorders (SSD) and most likely associated with abnormalities in affective, motor, and sensorimotor brain regions. However, contributions of different cortical features to the pathophysiology of catatonia in SSD are poorly understood. Here, T1-weighted structural magnetic resonance imaging data at 3 T were obtained from 56 right-handed patients with SSD. Using FreeSurfer version 6.0, we calculated cortical thickness, area, and local gyrification index (LGI). Catatonic symptoms were examined on the Northoff catatonia rating scale (NCRS). Patients with catatonia (NCRS total score ≥3; n = 25) showed reduced surface area in the parietal and medial orbitofrontal gyrus and LGI in the temporal gyrus (P < .05, corrected for cluster-wise probability [CWP]) as well as hypergyrification in rostral cingulate and medial orbitofrontal gyrus when compared with patients without catatonia (n = 22; P < .05, corrected for CWP). Following a dimensional approach, a negative association between NCRS motor and behavior scores and cortical thickness in superior frontal, insular, and precentral cortex was found (34 patients with at least 1 motor and at least 1 other affective or behavioral symptom; P < .05, corrected for CWP). Positive associations were found between NCRS motor and behavior scores and surface area and LGI in superior frontal, posterior cingulate, precentral, and pericalcarine gyrus (P < .05, corrected for CWP). The data support the notion that cortical features of distinct evolutionary and genetic origin differently contribute to catatonia in SSD. Catatonia in SSD may be essentially driven by cortex variations in frontoparietal regions including regions implicated in the coordination and goal-orientation of behavior.