Data-driven Neuroanatomical Subtypes in Various Stages of Schizophrenia: Linking cortical thickness, glutamate, and language functioning

The considerable variation in the spatial distribution of cortical thickness changes has been used to parse heterogeneity in schizophrenia. We aimed to recover a ‘cortical impoverishment’ subgroup with widespread cortical thinning. We applied hierarchical cluster analysis to cortical thickness data of three datasets in different stages of psychosis and studied the cognitive, functional, neurochemical, language and symptom profiles of the observed subgroups. Our consensus-based clustering procedure consistently produced a subgroup characterized by significantly lower cortical thickness. This ‘cortical impoverishment’ subgroup was associated with a higher symptom burden in a clinically stable sample and higher glutamate levels with language impairments in the first-episode sample. Overall, cortical thinning is more prevalent among patients, especially those with glutamate excess and speech dysfunctions in the early stages and higher residual symptom burden at later stages

Widespread cortical thinning, excessive glutamate and impaired linguistic functioning in schizophrenia: A cluster analytic approach

Introduction: Symptoms of schizophrenia are closely related to aberrant language comprehension and production. Macroscopic brain changes seen in some patients with schizophrenia are suspected to relate to impaired language production, but this is yet to be reliably characterized. Since heterogeneity in language dysfunctions, as well as brain structure, is suspected in schizophrenia, we aimed to first seek patient subgroups with different neurobiological signatures and then quantify linguistic indices that capture the symptoms of “negative formal thought disorder” (i.e., fluency, cohesion, and complexity of language production). Methods: Atlas-based cortical thickness values (obtained with a 7T MRI scanner) of 66 patients with first-episode psychosis and 36 healthy controls were analyzed with hierarchical clustering algorithms to produce neuroanatomical subtypes. We then examined the generated subtypes and investigated the quantitative differences in MRS-based glutamate levels [in the dorsal anterior cingulate cortex (dACC)] as well as in three aspects of language production features: fluency, syntactic complexity, and lexical cohesion. Results: Two neuroanatomical subtypes among patients were observed, one with near-normal cortical thickness patterns while the other with widespread cortical thinning. Compared to the subgroup of patients with relatively normal cortical thickness patterns, the subgroup with widespread cortical thinning was older, with higher glutamate concentration in dACC and produced speech with reduced mean length of T-units (complexity) and lower repeats of content words (lexical cohesion), despite being equally fluent (number of words). Conclusion: We characterized a patient subgroup with thinner cortex in first-episode psychosis. This subgroup, identifiable through macroscopic changes, is also distinguishable in terms of neurochemistry (frontal glutamate) and language behavior (complexity and cohesion of speech). This study supports the hypothesis that glutamate-mediated cortical thinning may contribute to a phenotype that is detectable using the tools of computational linguistics in schizophrenia

Synthesis of Isomerically Pure Multi-aniline C-60 Adducts with Cyclopentadienyl Addition Pattern

Unlike aliphatic amines, anilines cannot react directly with fullerenes to form isomerically pure fullerene multi-adducts. In the present work several anilino C-60 derivatives are prepared through BiCl3-mediated replacement reactions of C-60 derivatives that contain secondary amino addends. All new anilino C-60 derivatives have a cyclopentadienyl addition pattern and contain multiple anilino addends up to 5

Synthesis and Chemical Reactivity of Tetrahydro[60]fullerene Epoxides with Both Amino and Aryl Addends

Tetrahydro­[60]­fullerene epoxides C₆₀(O)­Ar_<i>n</i>(NR₂)_4–<i>n</i>, <i>n</i> = 1, 2, have been prepared by treating 1,4-adducts C₆₀(OH)­Ph and C₆₀(Tol)₂ with cyclic secondary amines. The epoxy moieties in these mixed tetrahydro[60]­fullerene epoxides were hydrolyzed into the corresponding diol derivatives, which were further oxidized into diketone open-cage fullerenes with a 10-membered orifice. A few other reactions also showed that the present tetrahydro[60]­fullerene epoxides with both amino and aryl addends exhibit improved chemical reactivity over the tetraamino[60]­fullerene epoxide without any aryl group

Pentafluorophenyl Transfer Reaction: Preparation of Pentafluorophenyl [60]Fullerene Adducts through Opening of Fullerene Epoxide Moiety with Trispentafluorophenylborane

Unlike the extensively studied perfluoroalkyl fullerene adducts, perfluorophenyl fullerene adducts are quite difficult to prepare by known methods. Trispentafluorophenylborane was found to react with fullerene epoxide to form the 1,2-perfluorophenylfullerenol. The method can be applied to both the simple epoxide C-60(O) and fullerene multiadducts containing an epoxide moiety. Single crystal X-ray structure analysis confirmed the addition of the pentafluorophenyl group

Data-driven Neurobiological Subtypes in Schizophrenia: A Scoping Review

Objective: To summarize evidence from studies that use unsupervised machine learning approaches to analyze neurobiological measurements in patients with schizophrenia spectrum disorders. Introduction: Neurobiological measurements obtained from patients often vary notably, complicating our ability to observe high effect-size differences in patients as a single group, compared to the unaffected, apparently healthy population. Research into the diagnosis, prognosis and treatment of schizophrenia could be better informed if this variation can be leverage to identify meaningful subgroups of patients. To tackle neurobiological heterogeneity, unsupervised machine learning approaches can be used to identify homogeneous bio-subtypes. However, the breadth and range of evidence are not yet comprehensively reviewed. Inclusion criteria: Studies met the following inclusion criteria: (1) studies that used unsupervised machine learning approaches or clustering methods (e.g., K-means, latent variable analysis) on neurobiological data to derive subgroups (2) studies conducted in patients diagnosed with schizophrenia spectrum disorders or other psychotic disorders as major sample of interest (3) studies published between 1946 and 2021. Methods: A scoping review was performed through searching PsycINFO, Medline, Embase, Scopus, and Web of Science electronic databases. Two reviewers independently screened and extracted the data on variables used, subtyping solutions as well as their strengths and implications

Synthesis and Chemical Reactivity of Tetrahydro[60]fullerene Epoxides with Both Amino and Aryl Addends

Tetrahydro­[60]­fullerene epoxides C₆₀(O)­Ar_<i>n</i>(NR₂)_4–<i>n</i>, <i>n</i> = 1, 2, have been prepared by treating 1,4-adducts C₆₀(OH)­Ph and C₆₀(Tol)₂ with cyclic secondary amines. The epoxy moieties in these mixed tetrahydro[60]­fullerene epoxides were hydrolyzed into the corresponding diol derivatives, which were further oxidized into diketone open-cage fullerenes with a 10-membered orifice. A few other reactions also showed that the present tetrahydro[60]­fullerene epoxides with both amino and aryl addends exhibit improved chemical reactivity over the tetraamino[60]­fullerene epoxide without any aryl group

Pentafluorophenyl Transfer Reaction: Preparation of Pentafluorophenyl [60]Fullerene Adducts through Opening of Fullerene Epoxide Moiety with Trispentafluorophenylborane

Unlike the extensively studied perfluoroalkyl fullerene adducts, perfluorophenyl fullerene adducts are quite difficult to prepare by known methods. Trispentafluorophenylborane was found to react with fullerene epoxide to form the 1,2-perfluorophenylfullerenol. The method can be applied to both the simple epoxide C₆₀(O) and fullerene multiadducts containing an epoxide moiety. Single crystal X-ray structure analysis confirmed the addition of the pentafluorophenyl group

Linguistic Profile Before, During and After the Onset of Psychosis: A Cluster Analysis

Background and hypothesis: “Oddities” in language and communication have historically been seen as a core feature of schizophrenia. The application of natural language processing (NLP) to speech samples can elucidate even the most subtle deviations in language. We aim to determine if speech-NLP based profiles that are distinctive of schizophrenia can be observed across the various clinical phases of psychosis. Design: Our sample consisted of 147 participants and included 39 healthy controls (HC), 72 were First-Episode Psychosis (FEP), 18 Chronic high-risk (CHR), 18 Schizophrenia (SZ). A structured task elicited 3 minutes of speech, which was then transformed into a quantitative measure on 12 linguistic variables (lexical, syntactic, semantic). Cluster analysis that leveraged healthy variations was then applied to determine linguistic subgroups. Results: We observed a three-cluster solution. The largest cluster, included most HC and the majority of patients, indicating a ‘Typical Linguistic Profile (TLP)’. One of the clusters had notably high semantic similarity in word choices with less perceptual words, lower cohesion and analytical structure; this cluster was almost entirely composed of patients in early stages of psychosis (EPP - Early Phase Profile). A second atypical cluster had more patients with established schizophrenia (SPP - Stable Phase Profile), with more perceptual but less cognitive/emotional word classes, simpler syntactic structure, and a lack of sufficient reference to prior information (reduced givenness). Conclusion: These findings provide insight into the differences in language at different stages of psychosis and their relevance to disease trajectories. Both EPP and SPP experienced detectable speech deviations and variations in disease burden