Schizophrenia Group Research Articles

Integrated Analysis of Gut microbiome, Inflammation and Neuroimaging Features Supports the Role of Microbiome-Gut-Brain Crosstalk in Schizophrenia

Abstract Background and Hypothesis Gut microbiota has been implicated in the pathogenesis of schizophrenia (SZ) and relevant changes in the brain, but the underlying mechanism remains elusive. This study aims to investigate the microbiota-gut-brain crosstalk centered on peripheral inflammation in SZ patients. Study Design We recruited a cohort of 182 SZ patients and 120 healthy controls (HC). Multi-omics data, including fecal 16S rRNA, cytokine data, and neuroimaging data, were collected and synthesized for analysis. Multi-omics correlations and mediation analyses were utilized to determine the associations of gut microbiome with inflammatory cytokines and neuroimaging characteristics. Additionally, machine learning models for effective SZ diagnosis were separately generated based on gut microbial and neuroimaging data. Study Results Gut microbial dysbiosis, characterized by a decrease in butyrate-producing bacteria and an increase in pro-inflammatory bacteria, has been identified in SZ patients. These key microbial taxa were associated with increased inflammatory cytokines, potentially through mediating lipid metabolic pathways such as steroid biosynthesis and linoleic acid metabolism. Further analysis revealed altered microbial genera to be correlated with disrupted gray matter volume and regional homogeneity in SZ patients. Importantly, certain inflammatory cytokines mediated the relationship between the SZ-enriched genus Succinivibrio and aberrant activity of anterior cingulate cortex and left inferior temporal gyrus in the SZ group. Moreover, the classification model based on gut microbial data showed comparable efficacy to the model based on brain functional signatures in SZ diagnosis. Conclusions This study presents evidence for the dysregulated microbiota-gut-brain axis in SZ and emphasizes the central role of peripheral inflammation.

Serum metabolic profile evidence for relationship between schizophrenia and depression: An untargeted metabolomics.

Given the genetic and clinical overlap observed between schizophrenia and depression, the present study was to identify the similarities and differences in serum metabolic profiles between patients with schizophrenia and depression. Global metabolomics research methods based on UHPLC-QTOF-MS/MS were performed. A total of 113 and 118 differential metabolites were screened and identified in depression and schizophrenia groups, respectively, as compared to health control; among those, 94 differential metabolites were shared by both. Pathway analysis indicated arginine and proline metabolism, alanine, aspartate, and glutamate metabolism were two significant metabolic pathways both in depression and schizophrenia groups as compared with health control groups, respectively. Similarly, 77 differential metabolites were identified between depression and schizophrenia groups, in which, serum N-acetylglutamine and isovalerylglycine levels showed significant differences between patients with depression and schizophrenia with p values less than 0.001 and without significant outliers. Sphingolipid metabolism was identified as a significant metabolic pathway distinguishing between depression and schizophrenia groups based on pathway analysis. Conclusively, common alterations in arginine and proline metabolism, alanine, aspartate, and glutamate metabolism were observed in patients with schizophrenia and depression; whereas differences in serum N-acetylglutamine and isovalerylglycine levels as well as sphingolipid metabolism were discovered between the two categories of patients.

Application of optical coherence tomography in neurodegenerative diseases: a focus on Parkinson’s, Alzheimer’s, and Schizophrenia in Bulgarian patients

This study investigates retinal alterations in patients with Alzheimer’s disease (AD), Parkinson’s disease (PD), and schizophrenia (SZ) using Optical Coherence Tomography (OCT). The primary objective was to determine whether these neurodegenerative diseases manifest in measurable retinal changes and to assess the impact of disease duration, medication use, and cognitive decline on these alterations. A cross-sectional observational design was employed, including 132 patients and age- and gender-matched controls. OCT imaging was performed using the Topcon 3D OCT-1 Maestro 2, focusing on the retinal nerve fibre layer (RNFL), ganglion cell complex (GCC), and macular thickness. Significant retinal thinning was observed in the AD and PD groups, correlating with disease severity and cognitive decline, and was more pronounced with longer disease duration. In contrast, no significant retinal changes were identified in the SZ group. The study also explored the effects of different drug classes, revealing correlations between specific medications and retinal parameters, particularly in the AD and PD cohorts. To our knowledge, this is the first study of its kind conducted with Bulgarian patients. These findings suggest that OCT may serve as a non-invasive biomarker for neurodegeneration in AD and PD, though its utility in SZ remains limited. Future research should aim to standardize OCT protocols, further investigate the potential of retinal imaging in tracking neurodegenerative disease progression, and explore its integration with other neuroimaging techniques for a more comprehensive diagnostic and monitoring approach.

Comparative Analysis of Fecal Microbiota Between Adolescents with Early-Onset Psychosis and Adults with Schizophrenia.

Studies of the composition of the gut microbiome have consistently shown that psychiatric disorders such as schizophrenia are associated with gut dysbiosis. However, research focusing on adolescents with early-onset psychosis remains limited. This study aimed to characterize the microbial communities and their potential metabolic functions in these populations. We identified that genera Desulfovibrionaceae_Incertae_Sedis, Paraprevotella, and several genera from the Oscillospiraceae family were significantly more abundant in patients with schizophrenia compared to non-psychotic individuals, while Dorea showed decreased levels in schizophrenia patients. Furthermore, patients with early-onset psychosis demonstrated a significant reduction in Staphylococcus abundance. Additionally, we observed an increase in Prevotellaceae Leyella and Prevotellaceae Incertae Sedis in patients receiving atypical antipsychotic treatment, along with a rise in the genus Weissella among those treated with sertraline. Conversely, patients on valproate treatment exhibited decreased levels of Desulfovibrionaceae Incertae Sedis, while showing increased levels of Kandleria and Howardella. Functional prediction analysis using PICRUSt2 revealed significant differences in the expression of key enzymes associated with fatty acid metabolism. Gene orthology analysis identified 10 differentially expressed genes in the early-onset psychosis and schizophrenia groups. Our findings underscore the importance of considering dietary factors, pharmacological treatments, and microbial composition in understanding the gut-brain axis in psychiatric disorders.

Help-seeking from traditional healers in patients with severe mental illness and its relationship with internalized stigma.

Help-seeking from traditional healers (TH) is common in patients with severe mental illness. However, the differences between patients with schizophrenia and bipolar disorder are not well-known. Although internalized stigma is also common in patients with severe mental illness, its impact on help-seeking from TH is not studied. To investigate help-seeking from TH and the relationship between help-seeking from TH and internalized stigma in patients with schizophrenia and bipolar disorder. In this cross-sectional study, we collected information about help-seeking from TH and clinical characteristics by using a semi-structured interview form from 310 patients with schizophrenia and bipolar disorder in two sites with different socio-cultural backgrounds. We measured internalized stigma by using The Internalized Stigma of Mental Illness (ISMI) scale. We found that 47% of the patients visited TH in any phase of their illness, and 46% of them sought help from TH before their first contact with a psychiatrist. Those who grew up in rural areas, were less educated, who attempted suicide before, with resistance to treatment, and with a family member who also admitted to TH were more frequent among the help-seekers from TH. This group also had more hospitalizations and higher Clinical Global Impression scores. Internalized stigma was found to be higher in the schizophrenia group, and it was related to help-seeking from TH and delay in admission to psychiatric facilities. Our findings suggest that help-seeking from TH is common both in patients with schizophrenia and bipolar disorder, and it has socio-cultural, illness-related, and stigma-related predictors.

Adenosine Metabolism Pathway Alterations in Frontal Cortical Neurons in Schizophrenia.

Schizophrenia is a neuropsychiatric illness characterized by altered neurotransmission, in which adenosine, a modulator of glutamate and dopamine, plays a critical role that is relatively unexplored in the human brain. In the present study, postmortem human brain tissue from the anterior cingulate cortex (ACC) of individuals with schizophrenia (n = 20) and sex- and age-matched control subjects without psychiatric illness (n = 20) was obtained from the Bronx-Mount Sinai NIH Brain and Tissue Repository. Enriched populations of ACC pyramidal neurons were isolated using laser microdissection (LMD). The mRNA expression levels of six key adenosine pathway components-adenosine kinase (ADK), equilibrative nucleoside transporters 1 and 2 (ENT1 and ENT2), ectonucleoside triphosphate diphosphohydrolases 1 and 3 (ENTPD1 and ENTPD3), and ecto-5'-nucleotidase (NT5E)-were quantified using real-time PCR (qPCR) in neurons from these individuals. No significant mRNA expression differences were observed between the schizophrenia and control groups (p > 0.05). However, a significant sex difference was found in ADK mRNA expression, with higher levels in male compared with female subjects (Mann-Whitney U = 86; p < 0.05), a finding significantly driven by disease (t(17) = 3.289; p < 0.05). Correlation analyses also demonstrated significant associations (n = 12) between the expression of several adenosine pathway components (p < 0.05). In our dementia severity analysis, ENTPD1 mRNA expression was significantly higher in males in the "mild" clinical dementia rating (CDR) bin compared with males in the "none" CDR bin (F(2, 13) = 5.212; p < 0.05). Lastly, antipsychotic analysis revealed no significant impact on the expression of adenosine pathway components between medicated and non-medicated schizophrenia subjects (p > 0.05). The observed sex-specific variations and inter-component correlations highlight the value of investigating sex differences in disease and contribute to the molecular basis of schizophrenia's pathology.

Quality of life (QOL) of patients with schizophrenia and epilepsy attending an outpatient clinic in a tertiary care hospital in Sri Lanka

Background: Schizophrenia and epilepsy are chronic relapsing disorders, that share common disadvantages that affects QOL.Methods: A cross-sectional descriptive study was conducted on 68 patients with schizophrenia and 68 patients with epilepsy, presenting to psychiatry and neurology clinics of the Colombo South Teaching Hospital (CSTH). The validated Sinhala and Tamil version of the WHO QOL 100 was used to assess the QOL.Results: Schizophrenia group had poorer QOL in physical (p&lt;0.05), social (p&lt;0.01), independence (p&lt;0.05) and environmental (p&lt;0.05) domains, compared to epilepsy. Longer duration of illness (&gt; 5 years) was associated with poorer QOL in the independence (p&lt;0.05) and social domains (p&lt;0.05) and longer duration of untreated illness was associated with lower QOL in the physical (p&lt;0.01) and social domains (p&lt;0.01) in schizophrenia group.Conclusions: Patients with schizophrenia had poorer QOL compared to patients with epilepsy. Longer duration of untreated illness was associated with poorer QOL in both groups.

The effect of childhood trauma on moral cognition in patients with schizophrenia.

The aim of this study was to investigate whether a potential moral cognitive impairment (failure in understanding moral rules) exists in patients with schizophrenia (SCZ) and to explore the effect of childhood trauma (CT) on moral cognition in a group of patients with SCZ. A total of 99 patients with SCZ and 102 healthy controls (HCs) were included in this study. The Childhood Trauma Questionnaire-Short Form (CTQ) was administered to assess childhood trauma experiences in both groups, while the Moral Identity Measure (MIM) and the Moral Foundations Questionnaire (MFQ) were applied for a comparative evaluation of moral cognition across the two groups. The Positive and Negative Syndrome Scale (PANSS) was administered to assess the psychopathology. Patients with schizophrenia had significantly greater CTQ scores than HCs (42.77 ± 13.50 vs. 29.11 ± 4.25, t=9.697, p<0.001). The prevalence of childhood trauma (χ 2 = 58.452, p<0.001) and history of aggressive behaviors (χ 2 = 23.565, p=0.001) among patients with SCZ were greater than that among HCs. In addition, the scores of moral cognition (MIM: 61.82 ± 15.12 vs. 70.88 ± 8.87, p=0.001; MFQ: 87.24 ± 22.30 vs. 112.62 ± 23.42, p=0.045) in the SCZ group was lower than that in the HC group after controlling for the influence of CT covariates. The MFQ score was negatively correlated with the CTQ score, the emotional abuse (EA) score, the physical abuse (PA) score and the physical neglect (PN) score in SCZ patients. Among HCs, the MFQ score was positively correlated with the CTQ score, as well as with the dimensions of physical abuse (PA) and emotional Neglect (EN). Multiple linear regression analyses revealed that impaired moral cognition performance was significantly predicted by the CTQ score (beta=-0.235, p=0.034, 95% CI -0.743 to -0.031) in patients with SCZ but was significantly predicted by years of education (beta=-0.392, p<0.001, 95% CI -4.783 to -1.876), alcohol use (beta=0.210, p=0.023, 95% CI 2.191 to 29.399) and the CTQ score (beta=0.184, p=0.046, 95% CI 0.019 to 1.928) in HCs. CTQ moderated the effect of SCZ on MFQ (B = 0.516); Simple tests revealed that the group effect on the MFQ was B=12.306 at the lower level(-1SD) and B = 54.089 at the higher level(+1SD) of the CTQ scores. SCZ patients exhibit impaired moral cognition. The contribution of CT to the presence of moral cognitive impairments seems to be independent of psychopathology.

Altered sense of agency in schizophrenia: the aberrant effect of cardiac interoceptive signals.

Schizophrenia (SZ) is characterized by abnormalities in self-representation, including a disturbed sense of agency (SoA). The continuous processing of sensory information concerning the internal state of the body (interoception) is argued to be fundamental to neural representations of the self. We, therefore, tested if aberrant interoception underpins disturbances in SoA in SZ, focusing on cardiac interoceptive signaling. Forty-two SZ and 29 non-clinical participants (healthy controls; HC) performed an intentional binding task to measure SoA during concurrent heartbeat recording. The effect of cardiac interoceptive signals on SoA was measured by the difference in intentional binding effect during systole and diastole. This measure was standardized based on the overall intentional binding effect to control for non-cardiac factors, and then compared between SZ and HC. Our study revealed a significant difference between SZ and HC groups, with opposite effects of cardiac systole on SoA. Specifically, cardiac systole disrupted SoA in SZ, contrasting with the enhanced SoA in HC. Across the SZ group, the extent to which SoA was disrupted by cardiac systole correlated significantly with a clinical proxy for symptom instability, namely the number of hospital admissions for hallucinations and delusions. Furthermore, the disruption was particularly observed in patients with severe hallucinations. This study revealed a disturbance in the impact of cardiac interoceptive signals on an implicit index of SoA in schizophrenia. This supports the notion that pathophysiological disruption of the central integration of interoceptive information increases vulnerability to disturbances in self-representation and the associated expression of schizophrenic symptoms.

Dynamic brain entropy predicts risky decision-making across transdiagnostic dimensions of psychopathology

ObjectivesMaladaptive risky decision-making is a common pathological behavior among patients with various psychiatric disorders. Brain entropy, which measures the complexity of brain time series signals, provides a novel approach to assessing brain health. Despite its potential, the dynamics of brain entropy have seldom been explored. This study aimed to construct a dynamic model of brain entropy and examine its predictive value for risky decision-making in patients with mental disorders, utilizing resting-state functional magnetic resonance imaging (rs-fMRI). MethodsThis study analyzed the rs-fMRI data from a total of 198 subjects, including 48 patients with bipolar disorder (BD), 47 patients with schizophrenia (SZ), 40 patients with adult attention deficit hyperactivity disorder (ADHD), as well as 63 healthy controls (HC). Time series signals were extracted from 264 brain regions based on rs-fMRI. The traditional static entropy and dynamic entropy (coefficient of variation, CV; rate of change, Rate) were constructed, respectively. Support vector regression was employed to predict risky decision-making utilizing leave-one-out cross-validation within each group. ResultsOur findings showed that CV achieved the best performances in HC and BD groups (r = −0.58, MAE = 6.43, R2 = 0.32; r = −0.78, MAE = 12.10, R2 = 0.61), while the Rate achieved the best in SZ and ADHD groups (r = −0.69, MAE = 10.20, R2 = 0.47; r = −0.78, MAE = 7.63, R2 = 0.60). For the dynamic entropy, the feature selection threshold rather than the time window length and overlapping ratio influenced predictive performance. ConclusionsThese results suggest that dynamic brain entropy could be a more effective predictor of risky decision-making than traditional static brain entropy. Our findings offer a novel perspective on exploring brain signal complexity and can serve as a reference for interventions targeting risky decision-making behaviors, particularly in individuals with psychiatric diagnoses.

Expression level of myocardial enzymes in patients with schizophrenia: Predictive value in the occurrence of violence

BACKGROUND Schizophrenic patients are prone to violence, frequent recurrence, and difficult to predict. Emotional and behavioral abnormalities during the onset of the disease, resulting in active myocardial enzyme spectrum. AIM To explored the expression level of myocardial enzymes in patients with schizophrenia and its predictive value in the occurrence of violence. METHODS A total of 288 patients with schizophrenia in our hospital from February 2023 to January 2024 were selected as the research object, and 100 healthy people were selected as the control group. Participants’ information, clinical data, and laboratory examination data were collected. According to Modified Overt Aggression Scale score, patients were further divided into the violent (123 cases) and non-violent group (165 cases). RESULTS The comparative analysis revealed significant differences in serum myocardial enzyme levels between patients with schizophrenia and healthy individuals. In the schizophrenia group, the violent and non-violent groups also exhibited different levels of serum myocardial enzymes. The levels of myocardial enzymes in the non-violent group were lower than those in the violent group, and the patients in the latter also displayed aggressive behavior in the past. CONCLUSION Previous aggressive behavior and the level of myocardial enzymes are of great significance for the diagnosis and prognosis analysis of violent behavior in patients with schizophrenia. By detecting changes in these indicators, we can gain a more comprehensive understanding of a patient’s condition and treatment.

Divergent pattern of functional connectivity within the dorsal attention network differentiates schizophrenia and bipolar disorder patients.

Schizophrenia (SZ) and bipolar disorder (BD) share common clinical features, symptoms, and neurocognitive deficits, which results in common misdiagnosis. Recently, it has been suggested that alterations within brain networks associated with perceptual organization yield potential to distinguish SZ and BD individuals. The aim of our study was to evaluate whether functional connectivity (FC) of the dorsal attention network (DAN) may differentiate both conditions. The study involved 90 participants: 30 remitted SZ patients, 30 euthymic BD patients, and 30 healthy controls (HC). Resting state functional magnetic resonance imaging was used to compare the groups in terms of the FC within the core nodes of the DAN involving frontal eye fields (FEF) and intraparietal sulcus (IPS). BD patients presented weaker inter-hemispheric FC between right and left FEF than HC. While SZ did not differ from HC in terms of inter-FEF connectivity, they presented increased inter- and intra-hemispheric FC between FEF and IPS. When compared with BD, SZ patients showed increased FC between right FEF and other nodes of the network (bilateral IPS and left FEF). We have shown that altered resting state FC within DAN differentiates BD, SZ, and HC groups. Divergent pattern of FC within DAN, consisting of hypoconnectivity in BD and hyperconnectivity in SZ, might yield a candidate biomarker for differential diagnosis between both conditions. More highly powered studies are needed to confirm these possibilities.

Multisensory perceptual and causal inference is largely preserved in medicated post-acute individuals with schizophrenia.

Hallucinations and perceptual abnormalities in psychosis are thought to arise from imbalanced integration of prior information and sensory inputs. We combined psychophysics, Bayesian modeling, and electroencephalography (EEG) to investigate potential changes in perceptual and causal inference in response to audiovisual flash-beep sequences in medicated individuals with schizophrenia who exhibited limited psychotic symptoms. Seventeen participants with schizophrenia and 23 healthy controls reported either the number of flashes or the number of beeps of audiovisual sequences that varied in their audiovisual numeric disparity across trials. Both groups balanced sensory integration and segregation in line with Bayesian causal inference rather than resorting to simpler heuristics. Both also showed comparable weighting of prior information regarding the signals' causal structure, although the schizophrenia group slightly overweighted prior information about the number of flashes or beeps. At the neural level, both groups computed Bayesian causal inference through dynamic encoding of independent estimates of the flash and beep counts, followed by estimates that flexibly combine audiovisual inputs. Our results demonstrate that the core neurocomputational mechanisms for audiovisual perceptual and causal inference in number estimation tasks are largely preserved in our limited sample of medicated post-acute individuals with schizophrenia. Future research should explore whether these findings generalize to unmedicated patients with acute psychotic symptoms.

Hyperactivity and altered functional connectivity of the ventral striatum in schizophrenia compared with bipolar disorder: A resting state fMRI study

BackgroundSchizophrenia patients frequently present with structural and functional abnormalities of the ventral striatum (VS). Methodswe examined basal activation state and functional connectivity (FC) in four subregions of the bilateral ventral striatum: left inferior ventral striatum (VSi_L), left superior ventral striatum(VSs_L), right inferior ventral striatum(VSi_R), and right superior ventral striatum(VSs_R). Resting-state functional magnetic resonance images were obtained from 62 schizophrenia patients (SCH), 57 bipolar disorder (BD) patients, and 26 healthy controls (HCs). ResultsThe schizophrenia group exhibited greater fALFF in bilateral VS subregions compared to BD and HC groups as well as greater FC between the bilateral VSi and multiple brain regions, including the thalamus, putamen, posterior cingulate gyrus (PCC), frontal cortex and caudate. Moreover, the fALFF values of the bilateral ventral striatum were positively correlated with the severity of positive symptoms. We also found the functional connectivity between the bilateral inferior ventral striatum and some brain regions aforementioned were positively correlated with the severity of negative symptoms. ConclusionThese findings confirm a crucial contribution of ventral striatum dysfunction, especially of the bilateral VSi in schizophrenia. Functionally dissociated regions of the ventral striatum are differentially disturbed in schizophrenia.

Pre-stimulus EEG phase coherence predicts visual target detection failures in schizophrenia: A pilot study

Impaired visual target detection is a common finding in schizophrenia that is linked to poor functional outcomes. However, the neural mechanisms that contribute to this deficit remain unclear. Recent research in healthy samples has identified relationships between the phase of pre-stimulus electroencephalographic (EEG) activity in the alpha band (8-12 Hz) or theta band (4-7 Hz) and the likelihood of visual target detection with and without attentional cueing, but these effects have not yet been explored in schizophrenia. We performed a study to investigate such effects in schizophrenia (n = 19) and healthy participants (n = 14), using a visual target detection task with attentional cues. We found significant relationships between pre-stimulus EEG phase properties and visual target detection in both groups, but also clear differences in the effects as a function of frequency, group, and attentional cueing. Alpha-band phase effects were relatively uniform across groups and conditions. By contrast, theta-band phase effects showed differences by group and attentional condition which could be consistent with attentional hyperfocusing in the schizophrenia group. Thus, our results elucidate a novel neural mechanism that may help to explain known impairments affecting both visual target detection and attention in schizophrenia.

Is there a relationship between resting state connectivity within large-scale functional networks and implicit motor learning impairments in schizophrenia and bipolar disorder?

The aim of this exploratory study is to evaluate whether implicit motor learning impairments observed in schizophrenia (SZ) and bipolar disorder (BD) are associated with the resting state functional connectivity (rs-FC) within large-scale functional networks. The study involved 30 BD patients, 30 SZ patients and 30 healthy controls (HC). Implicit motor learning was evaluated with the use of serial reaction time task (SRTT). Prior to the training patients underwent resting state functional magnetic resonance imaging (rsfMRI) examination. We have measured rs-FC within salience network (SAN), default mode network (DMN), frontoparietal network (FPN), sensorimotor network (SMN), limbic network (LN) and visual network (VIN) and their associations with implicit motor learning indices. rs-FC within SAN, DMN, FPN, SMN, LN and VIN reveal no significant association with implicit motor learning indices. BD, SZ and HC groups did not differ in terms of rs-FC within abovementioned networks. We have shown that in the studied groups SRTT performance could not be predicted by rs-FC within the major large-scale functional networks, i.e., SMN, FPN, VIN, LN, SAN and DMN. The observation of the independence of implicit motor learning from the initial activity of these systems is important for proper understanding of neuronal underpinnings of this process and planning further neuroimaging research on this topic.

The novel schizophrenia subgroup “major neurocognitive psychosis” is validated as a distinct class through the analysis of immune-linked neurotoxicity biomarkers and neurocognitive deficits

BackgroundUsing machine learning methods based on neurocognitive deficits and neuroimmune biomarkers, two distinct classes were discovered within schizophrenia patient samples. Increased frequency of psychomotor retardation, formal thought disorders, mannerisms, psychosis, hostility, excitation, and negative symptoms defined the first subgroup, major neurocognitive psychosis (MNP). Cognitive deficits in executive functions and memory and diverse neuroimmune aberrations were other MNP features. Simple neurocognitive psychosis (SNP) was the less severe phenotype. AimsThe study comprised a sample of 40 healthy controls and 90 individuals diagnosed with schizophrenia, divided into MNP and SNP based on previously determined criteria. Soft Independent Modelling of Class Analogy (SIMCA) was performed using neurocognitive test results and measurements of serum M1 macrophage and T helper-17 cytokines as discriminatory/modelling variables. The model-to-model distances between controls and MNP + SNP and between MNP and SNP were computed, and the top discriminatory variables were established. ResultsA notable SIMCA distance of 146.1682 was observed between MNP + SNP and the control group. The top-3 discriminatory variables were lowered motor speed, an activated T helper-17 axis, and lowered working memory. This study successfully differentiated MNP from SNP yielding a SIMCA distance of 19.3. M1 macrophage activation, lowered verbal fluency, and executive functions were the prominent features of MNP versus SNP. DiscussionBased on neurocognitive assessments and the immune-linked neurotoxic M1 and T helper-17 profiles, we found that MNP and SNP are qualitatively distinct classes. Future biomarker research should focus on examining biomarkers specifically in the MNP and SNP subgroups, rather than in the schizophrenia group.

Ketamine-dependent patients with persistent psychosis have higher neurofilament light chain levels than patients with schizophrenia

ObjectivesKetamine can induce persisting psychosis in a subset of individuals who use it chronically and heavily. Previously, we found that the psychopathology and cognitive impairments in patients with ketamine dependence (KD) exhibiting persistent psychosis (KPP) bear resemblances with schizophrenia, albeit with less severity in those with no persistent psychosis (KNP). Furthermore, we also showed that patients with KD had higher blood levels of neurofilament light chain (NFL), a biomarker for neuroaxonal injury, compared to healthy controls. In this study, we aimed to investigate the differences in NFL levels between patients with KPP and KNP while comparing the levels of individuals with schizophrenia and healthy controls. MethodsWe enrolled 64 treatment-seeking ketamine-dependent patients (53 with KNP and 11 with KPP), 37 medication-free patients with schizophrenia, and 80 healthy controls. Blood NFL levels were measured by single molecule array immunoassay. ResultsNFL levels were highest in the KPP subgroup, followed by the KNP subgroup, and then the schizophrenia and control groups (mean ± SD: 24.5 ± 24.7, 12.9 ± 10.9, 9.2 ± 12.2, and 6.2 ± 2.2 pg/mL, respectively), with no significant difference observed between the schizophrenia and control groups. ConclusionsWe found that KD is associated with higher NFL levels compared to schizophrenia, with the KPP subgroup showing the most consistent alterations. The observation of accentuated neuroaxonal pathology in individuals with KPP implies that this clinical manifestation is associated with a specific neurobiological phenotype, despite prior evidence suggesting syndromal similarity between schizophrenia and KPP.

Unveiling altered connectivity between cognitive networks and cerebellum in schizophrenia

Cognitive functioning is a crucial aspect in schizophrenia (SZ), and when altered it has devastating effects on patients' quality of life and treatment outcomes. Several studies suggested that they could result from altered communication between the cortex and cerebellum. However, the neural correlates underlying these impairments have not been identified. In this study, we investigated resting state functional connectivity (rsFC) in SZ patients, by considering the interactions between cortical networks supporting cognition and cerebellum. In addition, we investigated the relationship between SZ patients' rsFC and their symptoms.We used fMRI data from 74 SZ patients and 74 matched healthy controls (HC) downloaded from the publicly available database SchizConnect. We implemented a seed-based connectivity approach to identify altered functional connections between specific cortical networks and cerebellum. We considered ten commonly studied resting state networks, whose functioning encompasses specific cognitive functions, and the cerebellum, whose involvement in supporting cognition has been recently identified. We then explored the relationship between altered rsFC values and Positive and Negative Syndrome Scale (PANSS) scores.The SZ group showed increased connectivity values compared with HC group for cortical networks involved in attentive processes, which were also linked to PANSS items describing attention and language-related processing. We also showed decreased connectivity between cerebellar regions, and increased connectivity between them and attentive networks, suggesting the contribution of cerebellum to attentive and affective deficits.In conclusion, our findings highlighted the link between negative symptoms in SZ and altered connectivity within the cerebellum and between the same and cortical networks supporting cognition.

Assessment of resting cerebral perfusion between methamphetamine-associated psychosis and schizophrenia through arterial spin labeling MRI.

The clinical manifestations of methamphetamine (METH)-associated psychosis (MAP) and acute paranoid schizophrenia (SCZ) are similar. This study aims to assess regional cerebral blood flow (rCBF) in individuals who use METH and in those with SCZ using the MRI arterial spin labeling (ASL) technique. We prospectively recruited 68 participants and divided them into four groups: MAP (N = 15), SCZ (N = 13), METH users with no psychosis (MNP; N = 22), and normal healthy controls (CRL; N = 18). We measured rCBF using an MRI three-dimensional pseudo-continuous ASL sequence. Clinical variables were assessed using the Positive and Negative Syndrome Scale (PANSS) and Brief Assessment of Cognition in Schizophrenia (BACS). Group-level rCBF differences were analyzed using a two-sample t-test. Decreased rCBF was found in the precuneus, premotor cortex, caudate nucleus, dorsolateral prefrontal cortex, and thalamus in the MNP group compared with the CRL group. The MAP group had significantly decreased rCBF in the precuneus, hippocampus, anterior insula, inferior temporal gyrus, inferior orbitofrontal gyrus, and superior occipital gyrus compared with the MNP group. Increased rCBF in the precuneus and premotor cortex was seen in the MAP group compared with the SCZ group. rCBF in the precuneus and premotor cortex significantly correlated negatively with the PANSS but correlated positively with BACS scores in the MAP and SCZ groups. METH exposure was associated with decreased rCBF in the precuneus and premotor cortex. Patients with MAP exhibited higher rCBF than those with SCZ, implying preserved insight and favorable outcomes. rCBF can therefore potentially serve as a diagnostic approach to differentiate patients with MAP from those with SCZ.