Parkinsonism, Psychomotor Slowing, Negative and Depressive Symptoms in Schizophrenia Spectrum and Mood Disorders: Exploring Their Intricate Nexus Using a Network Analytic Approach.

BACKGROUND AND HYPOTHESIS: Parkinsonism, psychomotor slowing, negative and depressive symptoms show evident phenomenological similarities across different mental disorders. However, the extent to which they interact with each other is currently unclear. Here, we hypothesized that parkinsonism is an independent motor abnormality showing limited associations with psychomotor slowing, negative and depressive symptoms in schizophrenia spectrum (SSD), and mood disorders (MOD). STUDY DESIGN: We applied network analysis and community detection methods to examine the interplay and centrality (expected influence [EI] and strength) between parkinsonism, psychomotor slowing, negative and depressive symptoms in 245 SSD and 99 MOD patients. Parkinsonism was assessed with the Simpson-Angus Scale (SAS). We used the Positive and Negative Syndrome Scale (PANSS) to examine psychomotor slowing (item #G7), negative symptoms (PANSS-N), and depressive symptoms (item #G6). STUDY RESULTS: In SSD and MOD, PANSS item #G7 and PANSS-N showed the largest EI and strength as measures of centrality. Parkinsonism had small or no influence on psychomotor slowing, negative and depressive symptoms in SSD and MOD. In SSD and MOD, exploratory graph analysis identified one community, but parkinsonism showed a small influence on its occurrence. Network Comparison Test yielded no significant differences between the SSD and MOD networks (global strength p value: .396 and omnibus tests p value: .574). CONCLUSIONS: The relationships between the individual domains followed a similar pattern in both SSD and MOD highlighting their transdiagnostic relevance. Despite evident phenomenological similarities, our results suggested that parkinsonism is more independent of negative and depressive symptoms than psychomotor slowing in both SSD and MOD.

Deciphering the interplay between psychopathological symptoms, sensorimotor, cognitive and global functioning: a transdiagnostic network analysis.

BACKGROUND: Understanding the relationship between psychopathology and major domains of human neurobehavioral functioning may identify new transdiagnostic treatment targets. However, studies examining the interrelationship between psychopathological symptoms, sensorimotor, cognitive, and global functioning in a transdiagnostic sample are lacking. We hypothesized a close relationship between sensorimotor and cognitive functioning in a transdiagnostic patient sample. METHODS: We applied network analysis and community detection methods to examine the interplay and centrality [expected influence (EI) and strength] between psychopathological symptoms, sensorimotor, cognitive, and global functioning in a transdiagnostic sample consisting of 174 schizophrenia spectrum (SSD) and 38 mood disorder (MOD) patients. All patients (n = 212) were examined with the Positive and Negative Syndrome Scale (PANSS), the Heidelberg Neurological Soft Signs Scale (NSS), the Global Assessment of Functioning (GAF), and the Brief Cognitive Assessment Tool for Schizophrenia consisted of trail making test B (TMT-B), category fluency (CF) and digit symbol substitution test (DSST). RESULTS: NSS showed closer connections with TMT-B, CF, and DSST than with GAF and PANSS. DSST, PANSS general, and NSS motor coordination scores showed the highest EI. Sensory integration, DSST, and CF showed the highest strength. CONCLUSIONS: The close connection between sensorimotor and cognitive impairment as well as the high centrality of sensorimotor symptoms suggests that both domains share aspects of SSD and MOD pathophysiology. But, because the majority of the study population was diagnosed with SSD, the question as to whether sensorimotor symptoms are really a transdiagnostic therapeutic target needs to be examined in future studies including more balanced diagnostic groups.

Distribution and frequency of clinical criteria and rating scales for diagnosis and assessment of catatonia in different study types.

BACKGROUND: A comprehensive assessment of catatonic symptoms is decisive for diagnosis, neuronal correlates, and evaluation of treatment response and prognosis of catatonia. Studies conducted so far used different cut-off criteria and clinical rating scales to assess catatonia. Therefore, the main aim of this study was to examine the frequency and distribution of diagnostic criteria and clinical rating scales for assessing catatonia that were used in scientific studies so far. METHODS: We conducted a systematic review using PubMed searching for articles using catatonia rating scales/criteria published from January 1st 1952 (introduction of catatonic schizophrenia to first edition of the Diagnostic and Statistical Manual of Mental Disorders [DSM]) up to December 5th, 2022. RESULTS: 1928 articles were considered for analysis. 1762 (91,39 %) studies used one and 166 (8,61 %) used ≥2 definitions of catatonia. However, 979 (50,7 %) articles did not report any systematic assessment of catatonia. As for clinical criteria, DSM criteria were used by the majority of studies (n = 290; 14.0 %), followed by International Classification of Diseases (ICD) criteria (n = 61; 2.9 %). The Bush-Francis Catatonia Rating Scale (BFCRS) was found to be by far the most frequently utilized scale (n = 464; 22.4 % in the respective years), followed by Northoff Catatonia Rating Scale (NCRS) (n = 31; 1.5 % in the respective years). CONCLUSION: DSM and ICD criteria as well as BFCRS and NCRS were most frequently utilized and can therefore be recommended as valid instruments for the assessment of catatonia symptomatology.

Microstructural white matter biomarkers of symptom severity and therapy outcome in catatonia: Rationale, study design and preliminary clinical data of the whiteCAT study.

The number of magnetic resonance imaging (MRI) studies on neuronal correlates of catatonia has dramatically increased in the last 10 years, but conclusive findings on white matter (WM) tracts alterations underlying catatonic symptoms are still lacking. Therefore, we conduct an interdisciplinary longitudinal MRI study (whiteCAT) with two main objectives: First, we aim to enroll 100 psychiatric patients with and 50 psychiatric patients without catatonia according to ICD-11 who will undergo a deep phenotyping approach with an extensive battery of demographic, psychopathological, psychometric, neuropsychological, instrumental and diffusion MRI assessments at baseline and 12 weeks follow-up. So far, 28 catatonia patients and 40 patients with schizophrenia or other primary psychotic disorders or mood disorders without catatonia have been studied cross-sectionally. 49 out of 68 patients have completed longitudinal assessment, so far. Second, we seek to develop and implement a new method for semi-automatic fiber tract delineation using active learning. By training supportive machine learning algorithms on the fly that are custom tailored to the respective analysis pipeline used to obtain the tractogram as well as the WM tract of interest, we plan to streamline and speed up this tedious and error-prone task while at the same time increasing reproducibility and robustness of the extraction process. The goal is to develop robust neuroimaging biomarkers of symptom severity and therapy outcome based on WM tracts underlying catatonia. If our MRI study is successful, it will be the largest longitudinal study to date that has investigated WM tracts in catatonia patients.

Extension, translation and preliminary validation of the Northoff Scale for Subjective Experience in Catatonia (NSSC).

BACKGROUND: In the last two decades, much neuroscientific research has been done on the pathomechanisms of catatonia. However, catatonic symptoms have mainly been assessed with clinical rating scales based on observer ratings. Although catatonia is often associated with strong affective reactions, the subjective domain of catatonia has simply been neglected in scientific research. METHODS: The main objective of this study was to modify, extend and translate the original German version of the Northoff Scale for Subjective Experience in Catatonia (NSSC) and to examine its preliminary validity and reliability. Data were collected from 28 patients diagnosed with catatonia associated with another mental disorder (6A40) according to ICD-11. Descriptive statistics, correlation coefficients, internal consistency and principal component analysis were employed to address preliminary validity and reliability of the NSSC. RESULTS: NSSC showed high internal consistency (Cronbach's alpha = 0.92). NSSC total scores were significantly associated with Northoff Catatonia Rating Scale (r = 0.50, p < .01) and Bush Francis Catatonia Rating Scale (r = 0.41, p < .05) thus supporting its concurrent validity. There was no significant association between NSSC total score and Positive and Negative Symptoms Scale total (r = 0.26, p = .09), Brief Psychiatric Rating Scale (r = 0.29, p = .07) and GAF (r = 0.03, p = .43) scores. CONCLUSION: The extended version of the NSSC consists of 26 items and was developed to assess the subjective experience of catatonia patients. Preliminary validation of the NSSC revealed good psychometric properties. NSSC is a useful tool for everyday clinical work to assess the subjective experience of catatonia patients.

[German version of the Northoff scale for subjective experience in catatonia (NSSC-dv) : A validated instrument for examination of the subjective experience in catatonia]. / Deutsche Version der Northoff Skala für subjektives Erleben bei Katatonie (NSSC-dv) : Ein validiertes Messinstrument zur Erfassung des subjektiven Erlebens bei Katatonie.

Patients with catatonia often show serious motor, affective and behavioral symptoms, behind which the subjective experience often remains hidden. Therefore, this study disseminates our own systematic empirical investigation of the subjective experience of catatonia patients to a German-speaking audience of clinicians and researchers. Based on current evidence and the clinical experience of the authors, the self-report questionnaire Northoff Scale for Subjective Experience in Catatonia (NSSC) was modified, extended and validated and now consists of 26 items capturing the subjective experience of catatonia in its clinical diversity. A total of 46 patients with catatonia according to the International Classification of Diseases (11th revision, ICD-11) were asked about their subjective experience during the acute phase of the disease using the NSSC. The NSSC showed high internal consistency (Cronbach's alpha = 0.91). The NSSC total score was significantly associated with the Northoff Catatonia Rating Scale (NCRS; r = 0.46; p < 0.05), the total score of the Positive and Negative Syndrome Scale (PANSS; r = 0.30; p < 0.05), the Brief Psychiatric Rating Scale (BPRS; r = 0.33; p < 0.05), and Trait Anxiety (STAI; r = 0.64; p < 0.01), supporting its validity. Preliminary validation of the NSSC revealed good psychometric properties. The NSSC is a useful instrument for routine clinical use to assess the subjective experience of patients with catatonia in order to provide tailored psychotherapeutic interventions.

Psychomotor slowing in schizophrenia is associated with cortical thinning of primary motor cortex: A three cohort structural magnetic resonance imaging study.

Psychomotor slowing (PS) is characterized by slowed movements and lower activity levels. PS is frequently observed in schizophrenia (SZ) and distressing because it impairs performance of everyday tasks and social activities. Studying brain topography contributing to PS in SZ can help to understand the underlying neurobiological mechanisms as well as help to develop more effective treatments that specifically target affected brain areas. Here, we conducted structural magnetic resonance imaging (sMRI) of three independent cohorts of right-handed SZ patients (SZ#1: n = 72, SZ#2: n = 37, SZ#3: n = 25) and age, gender and education matched healthy controls (HC) (HC#1: n = 40, HC#2: n = 37, HC#3: n = 38). PS severity in the three SZ cohorts was determined using the Positive and Negative Syndrome Scale (PANSS) item #G7 (motor retardation) and Trail-Making-Test B (TMT-B). FreeSurfer v7.2 was used for automated parcellation and segmentation of cortical and subcortical regions. SZ#1 patients showed reduced cortical thickness in right precentral gyrus (M1; p = 0.04; Benjamini-Hochberg [BH] corr.). In SZ#1, cortical thinning in right M1 was associated with PANSS item #G7 (p = 0.04; BH corr.) and TMT-B performance (p = 0.002; BH corr.). In SZ#1, we found a significant correlation between PANSS item #G7 and TMT-B (p = 0.005, ρ=0.326). In conclusion, PANSS G#7 and TMT-B might have a surrogate value for predicting PS in SZ. Cortical thinning of M1 rather than alterations of subcortical structures may point towards cortical pathomechanism underlying PS in SZ.

Structure/function interrelationships and illness insight in patients with schizophrenia: a multimodal MRI data fusion study.

Illness insight in schizophrenia (SZ) has an important impact on treatment outcome, integration into society and can vary over the course of the disorder. To deal with and treat reduced or absent illness insight, we need to better understand its functional and structural correlates. Previous studies showed regionally abnormal brain volume in brain areas related to cognitive control and self-reference. However, little is known about associations between illness insight and structural and functional network strength in patients with SZ. This study employed a cross-sectional design to examine structural and functional differences between patients with SZ (n = 74) and healthy controls (n = 47) using structural and resting-state functional magnetic resonance imaging (MRI). Voxel-based morphometry was performed on structural data, and the amplitude of low frequency fluctuations (ALFF) was calculated for functional data. To investigate abnormal structure/function interrelationships and their association with illness insight, we used parallel independent component analysis (pICA). Significant group (SZ vs. HC) differences were detected in distinct structural and functional networks, predominantly comprising frontoparietal, temporal and cerebellar regions. Significant associations were found between illness insight and two distinct structural networks comprising frontoparietal (pre- and postcentral gyrus, inferior parietal lobule, thalamus, and precuneus) and posterior cortical regions (cuneus, precuneus, lingual, posterior cingulate, and middle occipital gyrus). Finally, we found a significant relationship between illness insight and functional network comprising temporal regions (superior temporal gyrus). This study suggests that aberrant structural and functional integrity of neural systems subserving cognitive control, memory and self-reference are tightly coupled to illness insight in SZ.

Structural alterations of amygdala and hypothalamus contribute to catatonia.

At present, current diagnostic criteria and systems neglect affective symptom expression in catatonia. This potentially serious omission could explain why putative contributions of limbic system structures, such as amygdala, hippocampus or hypothalamus, to catatonia in schizophrenia spectrum disorders (SSD) have been scarcely investigated so far. To determine whether topographical alterations of the amygdala, hippocampus and hypothalamus contribute to catatonia in SSD patients, we conducted structural magnetic resonance imaging (MRI) of SSD patients with (SSD-Cat, n = 30) and without (SSD-nonCat, n = 28) catatonia as defined by a Northoff Catatonia Rating Scale (NCRS) total score of ≥3 and =0, respectively, in comparison with healthy controls (n = 20). FreeSurfer v7.2 was used for automated segmentation of the amygdala and its 9 nuclei, hippocampus and its 21 subfields and hypothalamus and its associated 5 subunits. SSD-Cat had significantly smaller anterior inferior hypothalamus, cortical nucleus of amygdala, and hippocampal fimbria volumes when compared to SSD-nonCat. SSD-Cat had significantly smaller amygdala, hippocampus and hypothalamus whole and subunit volumes when compared to healthy controls. In SSD-Cat according to DSM-IV-TR (n = 44), we identified positive correlations between Brief Psychiatric Rating Scale (BPRS) item #2 (reflecting anxiety) and respective amygdala nuclei as well as negative correlation between NCRS behavioral score and hippocampus subiculum head. The lower volumes of respective limbic structures involved in affect regulation may point towards central affective pathomechanisms in catatonia.

Cortical morphology and illness insight in patients with schizophrenia.

Insight into illness in schizophrenia (SZ) patients has a major impact on treatment adherence and outcome. Previous studies have linked distinct deviations of brain structure to illness insight, specifically in frontoparietal and subcortical regions. Some of these abnormalities are thought to reflect aberrant cortical development. In this study, we used cross-sectional data to examine associations between illness insight and two cortical surface markers that are known to follow distinct neurodevelopmental trajectories, i.e. cortical gyrification (CG) and thickness (CT). CG and CT was investigated in SZ patients (n = 82) and healthy controls (HC, n = 48) using 3 T structural magnetic resonance imaging. Illness insight in SZ patients was measured using the OSSTI scale, an instrument that provides information on two distinct dimensions of illness insight, i.e. treatment adherence (OSSTI-A) and identification of disease-related symptoms (OSSTI-I). CT and CG were computed using the Computational Anatomy Toolbox (CAT12). Whole-brain and regions-of-interest (ROI)-based analyses were performed. SZ patients showed higher CG in anterior cingulate, superior frontal and temporal gyrus and reduced CG in insular and superior frontal cortex when compared to HC. SZ patients showed decreased CT in pre- and paracentral, occipital, cingulate, frontoparietal and temporal regions. Illness insight in SZ patients was significantly associated with both CG and CT in the left inferior parietal lobule (OSSTI-A) and the right precentral gyrus (CG/OSSTI-A, CT/OSSTI-I). The data support a multi-parametric neuronal model with both pre- and postnatal brain developmental factors having an impact on illness insight in patients with SZ.

Characterizing the sensorimotor domain in schizophrenia spectrum disorders.

The rapidly evolving field of sensorimotor neuroscience reflects the scientific and clinical relevance of sensorimotor abnormalities as an intrinsic component of the disease process, e.g., in patients with schizophrenia spectrum disorders (SSD). Despite previous efforts, however, prevalence rates and relationships between different categories of sensorimotor abnormalities in SSD patients are still subject of ongoing debate. In this study, we examined five different categories of the sensorimotor domain (Neurological soft signs (NSS), parkinsonism, catatonia, akathisia, and tardive dyskinesia) according to well-established clinical ratings scales and the respective cut-off criteria in a sample of 131 SSD patients. We used a collection of statistical methods to better understand prevalence, overlap and heterogeneity, as well as psychopathological and cognitive correlates of sensorimotor abnormalities. 97.7% of the SSD patients considered by this study exhibited at least one categorically defined sensorimotor abnormality that tended to co-vary within three different sensorimotor subgroups (moderate, hyperkinetic and hypokinetic). Finally, hyperkinetic and hypokinetic groups differed significantly in their neurocognitive performance compared with the moderate group. The results suggest different patterns of clinical overlap, highlight the relationship between sensorimotor and cognitive domain and provide clues for further neurobiological studies.

Intrinsic neural network dynamics in catatonia.

Catatonia is a transnosologic psychomotor syndrome with high prevalence in schizophrenia spectrum disorders (SSD). There is mounting neuroimaging evidence that catatonia is associated with aberrant frontoparietal, thalamic and cerebellar regions. Large-scale brain network dynamics in catatonia have not been investigated so far. In this study, resting-state fMRI data from 58 right-handed SSD patients were considered. Catatonic symptoms were examined on the Northoff Catatonia Rating Scale (NCRS). Group spatial independent component analysis was carried out with a multiple analysis of covariance (MANCOVA) approach to estimate and test the underlying intrinsic components (ICs) in SSD patients with (NCRS total score ≥ 3; n = 30) and without (NCRS total score = 0; n = 28) catatonia. Functional network connectivity (FNC) during rest was calculated between pairs of ICs and transient changes in connectivity were estimated using sliding windowing and clustering (to capture both static and dynamic FNC). Catatonic patients showed increased static FNC in cerebellar networks along with decreased low frequency oscillations in basal ganglia (BG) networks. Catatonic patients had reduced state changes and dwelled more in a state characterized by high within-network correlation of the sensorimotor, visual, and default-mode network with respect to noncatatonic patients. Finally, in catatonic patients according to DSM-IV-TR (n = 44), there was a significant correlation between increased within FNC in cortico-striatal state and NCRS motor scores. The data support a neuromechanistic model of catatonia that emphasizes a key role of disrupted sensorimotor network control during distinct functional states.

Progress in sensorimotor neuroscience of schizophrenia spectrum disorders: Lessons learned and future directions.

The number of neuroimaging studies on movement disorders, sensorimotor, and psychomotor functioning in schizophrenia spectrum disorders (SSD) has steadily increased over the last two decades. Accelerated by the addition of the "sensorimotor domain" to the Research Domain Criteria (RDoC) framework in January 2019, neuroscience research on the role of sensorimotor dysfunction in SSD has gained greater scientific and clinical relevance. To draw attention to recent rapid progress in the field, we performed a triennial systematic review (PubMed search from January 1st, 2018 through December 31st, 2020), in which we highlight recent neuroimaging findings and discuss methodological pitfalls as well as challenges for future research. The identified magnetic resonance imaging (MRI) studies suggest that sensorimotor abnormalities in SSD are related to cerebello-thalamo-cortico-cerebellar network dysfunction. Longitudinal and interventional studies highlight the translational potential of the sensorimotor domain as putative biomarkers for treatment response and as targets for non-invasive neurostimulation techniques in SSD.

[The sensorimotor domain in the research domain criteria system: progress and perspectives]. / Die sensomotorische Domäne im Research-Domain-Criteria-System: Fortschritte und Perspektiven.

Over the past three decades research interest in hypokinetic, hyperkinetic, sensorimotor and psychomotor abnormalities in mental disorders has steadily increased. This development has led to an increasing number of scientific initiatives that have not only highlighted the clinical need for early detection of extrapyramidal motor symptoms, tardive dyskinesia and catatonia but also provided numerous neurobiological findings and clinically relevant results based on the pathology of the sensorimotor system in patients with mental disorders. In view of these developments in January 2019 the National Institute of Mental Health (NIMH) research domain criteria (RDoC) initiative introduced a sixth domain called the sensorimotor domain to address deficits in the sensorimotor system and associated behavioral abnormalities. To draw attention to the rapid progress just since the introduction of the sensorimotor domain, a 2-year (1 January 2019-18 February 2021) systematic review is presented highlighting recent neuroimaging findings and discussing challenges for future research. In summary, aberrant sensorimotor processing in mental disorders is associated with dysfunction of the cerebello-thalamo-motor cortex network, which interacts with (social)cognitive and affective systems. Initial longitudinal and interventional studies highlight the translational potential of the sensorimotor domain.

Structural alterations in brainstem, basal ganglia and thalamus associated with parkinsonism in schizophrenia spectrum disorders.

The relative roles of brainstem, thalamus and striatum in parkinsonism in schizophrenia spectrum disorder (SSD) patients are largely unknown. To determine whether topographical alterations of the brainstem, thalamus and striatum contribute to parkinsonism in SSD patients, we conducted structural magnetic resonance imaging (MRI) of SSD patients with (SSD-P, n = 35) and without (SSD-nonP, n = 64) parkinsonism, as defined by a Simpson and Angus Scale (SAS) total score of ≥ 4 and < 4, respectively, in comparison with healthy controls (n = 20). FreeSurfer v6.0 was used for segmentation of four brainstem regions (medulla oblongata, pons, superior cerebellar peduncle and midbrain), caudate nucleus, putamen and thalamus. Patients with parkinsonism had significantly smaller medulla oblongata (p = 0.01, false discovery rate (FDR)-corrected) and putamen (p = 0.02, FDR-corrected) volumes when compared to patients without parkinsonism. Across the entire patient sample (n = 99), significant negative correlations were identified between (a) medulla oblongata volumes and both SAS total (p = 0.034) and glabella-salivation (p = 0.007) scores, and (b) thalamic volumes and both SAS total (p = 0.033) and glabella-salivation (p = 0.007) scores. These results indicate that brainstem and thalamic structures as well as basal ganglia-based motor circuits play a crucial role in the pathogenesis of parkinsonism in SSD.

White matter microstructure alterations in cortico-striatal networks are associated with parkinsonism in schizophrenia spectrum disorders.

The specific role of white matter (WM) microstructure in parkinsonism among patients with schizophrenia spectrum disorders (SSD) is largely unknown. To determine whether topographical alterations of WM microstructure contribute to parkinsonism in SSD patients, we examined healthy controls (HC, n=16) and SSD patients with and without parkinsonism, as defined by Simpson-Angus Scale total score of ≥4 (SSD-P, n=33) or <4 (SSD-nonP, n=62). We used whole brain tract-based spatial statistics (TBSS), tractometry (along tract statistics using TractSeg) and graph analytics (clustering coefficient (CCO), local betweenness centrality (BC)) to provide a framework of specific WM microstructural changes underlying parkinsonism in SSD. Using these methods, post hoc analyses showed (a) decreased fractional anisotrophy (FA), as measured via tractometry, in the corpus callosum, corticospinal tract and striato-fronto-orbital tract, and (b) increased CCO, as derived by graph analytics, in the left orbitofrontal cortex (OFC) and left superior frontal gyrus (SFG), in SSD-P patients when compared to SSD-nonP patients. Increased CCO in the left OFC and SFG was associated with SAS scores. These findings indicate the prominence of OFC alterations and aberrant connectivity with fronto-parietal regions and striatum in the pathogenesis of parkinsonism in SSD. This study further supports the notion of altered "bottom-up modulation" between basal ganglia and fronto-parietal regions in the pathobiology of parkinsonism, which may reflect an interaction between movement disorder intrinsic to SSD and antipsychotic drug-induced sensorimotor dysfunction.

Synthesis and Characterisation of Nanocomposite Mo-Fe-B Thin Films Deposited by Magnetron Sputtering.

Several ternary phases are known in the Mo-Fe-B system. Previous ab initio calculations have predicted that they should exhibit a tempting mix of mechanical and magnetic properties. In this study, we have deposited Mo-Fe-B films with a Fe-content varying from 0-37 at.% using non-reactive DC (direct current) magnetron sputtering. The phase composition, microstructure, and mechanical properties were investigated using X-ray diffraction, scanning transmission electron microscopy, and nanoindentation measurements. Films deposited at 300 °C and with >7 at.% Fe are nanocomposites consisting of two amorphous phases: a metal-rich phase and a metal-deficient phase. Hardness and elastic modulus were reduced with increasing Fe-content from ~29 to ~19 GPa and ~526 to ~353 GPa, respectively. These values result in H3/E2 ratios of 0.089-0.052 GPa, thereby indicating brittle behaviour of the films. Also, no indication of crystalline ternary phases was observed at temperatures up to 600 °C, suggesting that higher temperatures are required for such films to form.

A neurodevelopmental signature of parkinsonism in schizophrenia.

While sensorimotor abnormalities in schizophrenia (SZ) are of increasing scientific interest, little is known about structural changes and their developmental origins that may underlie parkinsonism. This multimodal magnetic resonance imaging (MRI) study examined healthy controls (HC, n = 20) and SZ patients with (SZ-P, n = 38) and without (SZ-nonP, n = 35) parkinsonism, as defined by Simpson-Angus Scale total scores of ≥4 or ≤1, respectively. Using the Computational Anatomy Toolbox (CAT12), voxel- and surface-based morphometry were applied to investigate cortical and subcortical gray matter volume (GMV) and three cortical surface markers of distinct neurodevelopmental origin: cortical thickness (CTh), complexity of cortical folding (CCF) and sulcus depth. In a subgroup of patients (29 SZ-nonP, 25 SZ-P), resting-state fMRI data were also analyzed using a regions-of-interest approach based on fractional amplitude of low frequency fluctuations (fALFF). SZ-P patients showed increased CCF in the left supplementary motor cortex (SMC) and decreased left postcentral sulcus (PCS) depth compared to SZ-nonP patients (p < 0.05, FWE-corrected at cluster level). In SMC, CCF was associated negatively with activity, which also differed significantly between the patient groups and between patients and HC. In regression models, severity of parkinsonism was associated negatively with left middle frontal CCF and left anterior cingulate CTh. These data provide novel insights into altered trajectories of cortical development in SZ patients with parkinsonism. These cortical surface changes involve the sensorimotor system, suggesting abnormal neurodevelopmental processes tightly coupled with cortical activity and subcortical morphology that convey increased risk for sensorimotor abnormalities in SZ.

Generative network models of altered structural brain connectivity in schizophrenia.

Alterations in the structural connectome of schizophrenia patients have been widely characterized, but the mechanisms remain largely unknown. Generative network models have recently been introduced as a tool to test the biological underpinnings of altered brain network formation. We evaluated different generative network models in healthy controls (n=152), schizophrenia patients (n=66), and their unaffected first-degree relatives (n=32), and we identified spatial and topological factors contributing to network formation. We further investigated how these factors relate to cognition and to polygenic risk for schizophrenia. Our data show that among the four tested classes of generative network models, structural brain networks were optimally accounted for by a two-factor model combining spatial constraints and topological neighborhood structure. The same wiring model explained brain network formation across study groups. However, relatives and schizophrenia patients exhibited significantly lower spatial constraints and lower topological facilitation compared to healthy controls. Further exploratory analyses point to potential associations of the model parameter reflecting spatial constraints with the polygenic risk for schizophrenia and cognitive performance. Our results identify spatial constraints and local topological structure as two interrelated mechanisms contributing to regular brain network formation as well as altered connectomes in schizophrenia and healthy individuals at familial risk for schizophrenia. On an exploratory level, our data further point to the potential relevance of spatial constraints for the genetic risk for schizophrenia and general cognitive functioning, thereby encouraging future studies in following up on these observations to gain further insights into the biological basis and behavioral relevance of model parameters.