Non-deficit Schizophrenia Patients Research Articles

Altered patterns of dynamic functional connectivity of brain networks in deficit and non-deficit schizophrenia.

This study aims to investigate the altered patterns of dynamic functional network connectivity (dFNC) between deficit schizophrenia (DS) and non-deficit schizophrenia (NDS), and further explore the associations with cognitive impairments. 70 DS, 91 NDS, and 120 matched healthy controls (HCs) were enrolled. The independent component analysis was used to segment the whole brain. The fMRI brain atlas was used to identify functional networks, and the dynamic functional connectivity (FC) of each network was detected. Correlation analysis was used to explore the associations between altered dFNC and cognitive functions. Four dynamic states were identified. Compared to NDS, DS showed increased FC between sensorimotor network and default mode network in state 1 and decreased FC within auditory network in state 4. Additionally, DS had a longer mean dwell time of state 2 and a shorter one in state 3 compared to NDS. Correlation analysis showed that fraction time and mean dwell time of states were correlated with cognitive impairments in DS. This study demonstrates the distinctive altered patterns of dFNC between DS and NDS patients. The associations with impaired cognition provide specific neuroimaging evidence for the pathogenesis of DS.

Convergent and divergent genes expression profiles associated with brain-wide functional connectome dysfunction in deficit and non-deficit schizophrenia.

Deficit schizophrenia (DS) is a subtype of schizophrenia characterized by the primary and persistent negative symptoms. Previous studies have identified differences in brain functions between DS and non-deficit schizophrenia (NDS) patients. However, the genetic regulation features underlying these abnormal changes are still unknown. This study aimed to detect the altered patterns of functional connectivity (FC) in DS and NDS and investigate the gene expression profiles underlying these abnormal FC. The study recruited 82 DS patients, 96 NDS patients, and 124 healthy controls (CN). Voxel-based unbiased brain-wide association study was performed to reveal altered patterns of FC in DS and NDS patients. Machine learning techniques were used to access the utility of altered FC for diseases diagnosis. Weighted gene co-expression network analysis (WGCNA) was employed to explore the associations between altered FC and gene expression of 6 donated brains. Enrichment analysis was conducted to identify the genetic profiles, and the spatio-temporal expression patterns of the key genes were further explored. Comparing to CN, 23 and 20 brain regions with altered FC were identified in DS and NDS patients. The altered FC among these regions showed significant correlations with the SDS scores and exhibited high efficiency in disease classification. WGCNA revealed associations between DS/NDS-related gene expression and altered FC. Additionally, 22 overlapped genes, including 12 positive regulation genes and 10 negative regulation genes, were found between NDS and DS. Enrichment analyses demonstrated relationships between identified genes and significant pathways related to cellular response, neuro regulation, receptor binding, and channel activity. Spatial and temporal gene expression profiles of SCN1B showed the lowest expression at the initiation of embryonic development, while DPYSL3 exhibited rapid increased in the fetal. The present study revealed different altered patterns of FC in DS and NDS patients and highlighted the potential value of FC in disease classification. The associations between gene expression and neuroimaging provided insights into specific and common genetic regulation underlying these brain functional changes in DS and NDS, suggesting a potential genetic-imaging pathogenesis of schizophrenia.

Cognitive Dysfunctions Measured with the MCCB in Deficit and Non-Deficit Schizophrenia

This study compared cognitive domains between deficit schizophrenia (DS) and non-deficit schizophrenia (NDS) patients and healthy controls (HC), analyzing relationships between psychopathological dimensions and cognitive domains. A total of 29 DS patients, 45 NDS patients, and 39 HC subjects participated. Cognitive domains were measured using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Battery. Psychopathological symptoms were evaluated with the Positive and Negative Syndrome Scale. Clinical groups performed poorer than HC groups in regards to speed of processing, attention/vigilance, working memory, verbal and visual learning and memory, reasoning and problem solving, and social cognition. DS patients scored poorer than NDS patients in terms of all cognitive domains and the overall score, except for reasoning and problem solving. Positive, negative, disorganization, and resistance symptoms were related to cognitive functions only in NDS patients. Our findings suggest that the MCCB battery is sensitive to detecting cognitive dysfunctions in both deficit and non-deficit schizophrenia.

Executive Functions and Psychopathology Dimensions in Deficit and Non-Deficit Schizophrenia

This study: (a) compared executive functions between deficit (DS) and non-deficit schizophrenia (NDS) patients and healthy controls (HC), controlling premorbid IQ and level of education; (b) compared executive functions in DS and NDS patients, controlling premorbid IQ and psychopathological symptoms; and (c) estimated relationships between clinical factors, psychopathological symptoms, and executive functions using structural equation modelling. Participants were 29 DS patients, 44 NDS patients, and 39 HC. Executive functions were measured with the Mazes Subtest, Spatial Span Subtest, Letter Number Span Test, Color Trail Test, and Berg Card Sorting Test. Psychopathological symptoms were evaluated with the Positive and Negative Syndrome Scale, Brief Negative Symptom Scale, and Self-evaluation of Negative Symptoms. Compared to HC, both clinical groups performed poorer on cognitive flexibility, DS patients on verbal working memory, and NDS patients on planning. DS and NDS patients did not differ in executive functions, except planning, after controlling premorbid IQ and negative psychopathological symptoms. In DS patients, exacerbation had an effect on verbal working memory and cognitive planning; in NDS patients, positive symptoms had an effect on cognitive flexibility. Both DS and NDS patients presented deficits, affecting the former to a greater extent. Nonetheless, clinical variables appeared to significantly affect these deficits.

Differences in inflammatory marker profiles and cognitive functioning between deficit and nondeficit schizophrenia.

Deficit schizophrenia (DS) patient is a homogenous subtype of schizophrenia that includes primary and enduring negative symptoms. This study aimed to compare the differences in cognitive functioning and plasma levels of C-reactive protein (CRP) and inflammatory cytokines among DS patients, nondeficit schizophrenia (NDS) patients, and healthy controls (HCs). A total of 141 schizophrenia patients and 67 HCs were included in this study. The schizophrenia patients were divided into DS (N= 51) and NDS (N=90) groups based on the Proxy for the Deficit Syndrome Scale (PDS). The Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were used to evaluate the clinical symptoms and cognitive performances, respectively. The plasma level of CRP, IL-1β, Il-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, TNF-α, and IFN-γ were measured using enzyme-linked immunosorbent assays (ELISAs). Our results showed that DS patients had the worst cognitive performance, especially in the immediate memory, attention, and language dimensions, compared to the NDS and HC groups. Compared to the HCs group, DS patients had higher levels of CRP, IL-1β, IL-6, IL-8, IFN-γ, and total proinflammatory cytokines, and NDS patients had higher levels of IL-1β, IFN-γ, and proinflammatory cytokines. We also found that CRP levels were significantly increased in DS patients compared to NDS patients. Moreover, stepwise logistic regression analysis revealed that CRP is an independent risk factor for DS. Sex stratification analysis showed significant differences in almost all cytokines in female samples but not in male samples. The significant differences in cognitive performance and inflammatory components among groups suggest that deficit syndrome is an independent endophenotype of schizophrenia patients with unique immune-inflammatory features, but may have sex characteristics.

Serum BDNF levels, glycolipid metabolism in deficit schizophrenia: A case-control study.

Few studies have compared serum BDNF and glycolipid profiles in patients with deficit schizophrenia (DS) and non-deficit schizophrenia (NDS). We aimed to compare BDNF and glycolipid profiles between DS and NDS patients and healthy controls, and to investigate the relationship between BDNF, glycolipid profiles in DS and NDS patients. A total of 591 patients with chronic schizophrenia (SZ) and 238 healthy controls participated in this study. According to Proxy for the Deficit Syndrome Scale, SZ patients were divided into DS (n=158) and NDS (n=273) patients. Psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Serum BDNF levels were measured using enzyme-linked immunosorbent assay (ELISA). BDNF levels were significantly lower in SZ patients than those in healthy controls (7.81±2.98ng/ml vs. 11.96±2.29ng/ml, P<0.01). Furthermore, BDNF levels were lower in DS group than those in NDS group (P=0.007, OR=0.846, 95% CI=0.750-0.955). Lower triglyceride levels were also an independent predictor for DS patients (P=0.007, OR=0.846, 95% CI=0.750-0.955). Serum BDNF levels were negatively associated with the severity of deficit syndrome in SZ patients (β=-1.151, t= -2.559, P=0.011). In DS group, triglycerides were associated with PANSS negative subscore (β=-0.262, t= -2.994, P=0.003) and depressive factor subscore (β=0.282, t= 2.146, P=0.035). Serum BDNF and triglycerides may be informative biomarkers of DS in SZ patients. The differences in glycolipid metabolism patterns between DS and NDS patients indicate that deficit syndrome is an independent endophenotype of SZ patients.

Psychopathology and Integrity of the Superior Longitudinal Fasciculus in Deficit and Nondeficit Schizophrenia.

The superior longitudinal fasciculus (SLF) is a white matter bundle that connects the frontal areas with the parietal areas. As part of the visuospatial attentional network, it may be involved in the development of schizophrenia. Deficit syndrome (DS) is characterized by primary and enduring negative symptoms. The present study assessed SLF integrity in DS and nondeficit schizophrenia (NDS) patients and examined possible relationships between it and psychopathology. Twenty-six DS patients, 42 NDS patients, and 36 healthy controls (HC) underwent psychiatric evaluation and diffusion tensor imaging (DTI). After post-processing, fractional anisotropy (FA) values within the SLF were analyzed. Psychopathology was assessed with the Positive and Negative Syndrome Scale, Brief Negative Symptom Scale, and Self-evaluation of Negative Symptoms. The PANSS proxy for the deficit syndrome was used to diagnose DS. NDS patients had lower FA values than HC. DS patients had greater negative symptoms than NDS patients. After differentiating clinical groups and HC, we found no significant correlations between DTI measures and psychopathological dimensions. These results suggest that changes in SLF integrity are related to schizophrenia, and frontoparietal dysconnection plays a role in its etiopathogenesis. We confirmed that DS patients have greater negative psychopathology than NDS patients. These results are preliminary; further studies are needed.

Eye movement characteristics in male patients with deficit and non-deficit schizophrenia and their relationships with psychiatric symptoms and cognitive function

BackgroundThe cognitive impairment pattern of deficit schizophrenia (DS) is centered on an impaired attention function. Previous studies have suggested that the exploratory eye movement (EEM) tests reflect attention deficits in patients with schizophrenia. However, no study has investigated the characteristics of eye movement in DS in the Chinese Han population. This study aimed to investigate the pattern of eye movement characteristics in DS patients and to examine whether eye movement characteristic is associated with serious negative symptoms and cognitive decline in this schizophrenia subtype.MethodsA total of 86 male patients [37 DS and 49 non-deficit schizophrenia (NDS)] and 80 healthy controls (HC) participated in this study. Clinical symptoms were assessed using the Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS). Cognitive function was assessed using the Mattis Dementia Rating Scale (MDRS-2). Eye movement data of subjects were collected using an eye movement tracking analyzer.ResultsThere were significant differences in the overall eye movement data and cognitive test scores among the three groups (all P < 0.001). Both DS and NDS schizophrenia subgroups showed more severe eye movement and cognitive impairment compared with the control group. The number of eye fixations (NEF), total of eye scanning length (TESL), and cognitive function in DS patients were significantly lower than those in NDS patients. The discriminant analysis (D score) was higher than that of the control group (P < 0.001). In the DS group, the inattention factor of SANS was negatively correlated with the attention factor (r = − 0.545, P = 0.001) and structure factor of cognitive (r = − 0.389, P = 0.023), the affective flattening factor of SANS was negatively correlated with TESL (r = − 0.353, P = 0.041) and initiation/retention factor of cognitive (r = − 0.376,P = 0.028). TESL was found to positively correlate with the MDRS-2 total score (r = 0.427, P = 0.012), attention factor (r = 0.354, P = 0.040), and memory factor (r = 0.349, P = 0.043) in the DS group, whereas the mean of eye scanning length (MESL) positively correlated with cognitive impairments in the NDS group. The negative symptoms showed no significant correlation with cognition in the NDS group.ConclusionsTotal of eye scanning length may be a characteristic eye movement symptom in DS patients, which is associated with serious negative symptoms and cognitive impairment in this schizophrenia subtype.

Aberrant large-scale brain modules in deficit and non-deficit schizophrenia

ObjectiveSchizophrenia is a heterogenous psychiatric disease, and deficit schizophrenia (DS) is a clinical subgroup with primary and enduring negative symptoms. Although previous neuroimaging studies have identified functional connectome alterations in schizophrenia, the modular organizations in DS and nondeficit schizophrenia (NDS) remain poorly understood. Therefore, this study aimed to investigate the modular-level alterations in DS patients compared with the NDS and healthy control (HC) groups. MethodsA previously collected dataset was re-analyzed, in which 74 chronic male schizophrenia patients (33 DS and 41 NDS) and 40 HC underwent resting-state functional magnetic resonance imaging with eyes closed in a Siemens 3 T scanner (scanning duration = 8 min). Modular- (intramodule and intermodule connectivity) and nodal- [normalized within-module degree (Zi) and participation coefficient (PCi)] level graph theory properties were computed and compared among the three groups. Receiver operating characteristic curve (ROC) analyses were performed to examine the classification ability of these measures, and partial correlations were conducted between network measures and symptom severity. Validation analyses on head motion, network sparsity, and parcellation scheme were also performed. ResultsBoth schizophrenia subgroups showed decreased intramodule connectivity in salience network (SN), somatosensory-motor network (SMN), and visual network (VN), and increased intermodule connectivity in SMN-default mode network (DMN) and SMN-frontoparietal network (FPN). Compared with NDS patients, DS patients showed weaker intramodule connectivity in SN and stronger intermodule connectivity in SMN-FPN and SMN-VN. At the nodal level, the schizophrenia-related alterations were distributed in SN, SMN, VN, and DMN, and 7 DS-specific nodal alterations were identified. Intramodule connectivity of SN, intermodule connectivity of SMN-VN, and Zi of left precuneus successfully distinguished the three groups. Partial correlational analyses revealed that these measures were related to negative symptoms, general psychiatric symptoms, and neurocognitive function. ConclusionOur findings suggest that functional connectomes, especially SN, SMN, and VN, may capture the distinct and common disruptions of DS and NDS. These findings may help to understand the neuropathology of negative symptoms of schizophrenia and inform targets for treating different schizophrenia subtypes.

Altered Functional Connectivity of the Nucleus Accumbens Network Between Deficit and Non-deficit Schizophrenia.

Deficit schizophrenia (DS), which is marked by stable negative symptoms, is regarded as a homogeneous subgroup of schizophrenia. While DS patients have structurally altered nucleus accumbens (NAcc) compared to non-deficit schizophrenia (NDS) patients and healthy individuals, the investigation of NAcc functional connectivity (FC) with negative symptoms and neurocognition could provide insights into the pathophysiology of schizophrenia. 58 DS, 93 NDS, and 113 healthy controls (HCs) underwent resting-state functional magnetic resonance (rsfMRI). The right and left NAcc were respectively used as seed points to construct the functional NAcc network in whole-brain FC analysis. ANCOVA compared the differences in NAcc network FC and partial correlation analysis explored the relationships between altered FC of NAcc, negative symptoms and neurocognition. Compared to HCs, both DS and NDS patients showed decreased FC between the left NAcc (LNAcc) and bilateral middle cingulate gyrus, and between the right NAcc (RNAcc) and right middle frontal gyrus (RMFG), as well as increased FC between bilateral NAcc and bilateral lingual gyrus. Moreover, the FC between the LNAcc and bilateral calcarine gyrus (CAL) was lower in the DS group compared to NDS patients. Correlation analysis indicated that FC value of LNAcc-CAL was negatively correlated to negative symptoms. Furthermore, aberrant FC values within the NAcc network were correlated with severity of clinical symptoms and neurocognitive impairments in DS and NDS patients. This study demonstrated abnormal patterns of FC in the NAcc network between DS and NDS. The presence of altered LNAcc-CAL FC might be involved in the pathogenesis of negative symptoms in schizophrenia.

White Matter Integrity of the Corpus Callosum and Psychopathological Dimensions in Deficit and Non-Deficit Schizophrenia Patients.

Deficit syndrome (DS) is a subtype of schizophrenia characterized by primary persistent negative symptoms. The corpus callosum (CC) appears to be related to psychopathology in schizophrenia. This study assessed white matter integrity in the CC using diffusion tensor imaging (DTI) in deficit and non-deficit schizophrenia (NDS) patients. We also investigated the psychopathological dimensions of schizophrenia and their relationship to CC integrity. Fifteen DS patients, 40 NDS patients, and 30 healthy controls (HC) underwent psychiatric evaluation and neuroimaging. We divided the CC into five regions and assessed their fractional anisotropy (FA) and mean diffusivity (MD). Psychopathology was assessed with the Positive and Negative Syndrome Scale. DS patients had lower FA than NDS patients and HC, and higher MD in Region 5 of the CC than did HC. NDS patients had higher MD in Region 4 of the CC. The patient groups differed in terms of negative symptoms. After differentiating clinical groups and HC, no significant correlations were observed between DTI measures and psychopathological symptoms. Our results suggest that DS and NDS are characterized by minor impairments of the posterior CC. We confirmed that DS patients have greater negative psychopathology than NDS patients. Our results are preliminary, and further studies are needed.

Serum C-Reactive Protein in Patients with Deficit Schizophrenia and the Relationship with Cognitive Function.

BackgroundSerum levels of C-reactive protein (CRP) were measured in patients with deficit schizophrenia (DS) to confirm the association between CRP level and cognitive performance and to determine whether CRP was a new biological indicator with the potential clinical applications in DS patients.MethodsThree independent samples [41 DS and 50 non-deficit schizophrenia (NDS) and 30 sex- and age-matched healthy controls (HCs)] were recruited in our study. Serum CRP levels were measured by immunofluorescence. The Positive and Negative Syndrome Scale (PANSS) and alternative forms of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were also assessed. And the relationships between serum CRP levels and both PANSS and RBANS scores were finally analyzed.ResultsThe results of serum CRP level were showed significantly different among the three groups and increased from the HCs to NDS patients to DS patients. There were also significant differences in the cognitive subdomain analyses among the three groups. Serum CRP levels were found positively correlated with total and negative PANSS scores, and showed negatively correlated with overall cognitive test scores in the DS samples.ConclusionSerum C-reactive protein levels and their association with cognitive performance were different between deficit schizophrenia and non-deficit schizophrenia samples, and higher serum CRP level was associated with worse cognitive performance in the DS patients. The results indicated that CRP could be a potential biomarker, and DS could be a distinct subset of schizophrenia.

Association between DRD2 and ANKK1 polymorphisms with the deficit syndrome in schizophrenia

BackgroundThe clinical course of schizophrenia varies among patients and is difficult to predict. Some patient populations present persistent negative symptoms, referred to as the deficit syndrome. Compared to relatives of non-deficit schizophrenia patients, family members of this patient population are at an increased risk of developing schizophrenia. Therefore, the aim of this study was to search for genetic underpinnings of the deficit syndrome in schizophrenia.MethodsThree SNPs, i.e., rs1799732 and rs6276 located within DRD2, and rs1800497 within ANKK1, were identified in the DNA samples of 198 schizophrenia probands, including 103 patients with deficit (DS) and 95 patients with non-deficit schizophrenia (NDS). Results: No significant differences concerning any of the analyzed polymorphisms were found between DS and NDS patients. However, significant links were observed between family history of schizophrenia and the deficit syndrome, G/G genotype and rs6276 G allele. In a separate analysis, we identified significant differences in frequencies of rs6276 G allele between DS and NDS patients with family history of schizophrenia. No significant associations were found between DRD2 and ANKK1 SNPs and the age of onset or schizophrenia symptom severity.ConclusionsThe results of our preliminary study fail to provide evidence of associations between DRD2 and ANKK1 polymorphisms with the deficit syndrome or schizophrenia symptom severity, but suggest potential links between rs6276 in DRD2 and the deficit syndrome in patients with hereditary susceptibility to schizophrenia. However, further studies are necessary to confirm this observation.

Cerebral white matter changes in deficit and non-deficit subtypes of schizophrenia.

The considerable clinical heterogeneity in schizophrenia makes elucidation of its neurobiology challenging. Subtyping the disorder is one way to reduce this heterogeneity and deficit status is one such categorization based on the prominence of negative symptoms. We aimed to utilize diffusion tensor imaging (DTI) to identify unique white matter cerebral changes in deficit schizophrenia (DS) compared with non-deficit schizophrenia (NDS) and healthy controls (HC) in an Asian sample. A total of 289 subjects (111 HC, 133 NDS and 45 DS) underwent DTI and completed rating scales which assessed the severity of psychopathology, psychosocial functioning and premorbid intelligence.We found that DS patients had fractional anisotropy (FA) reductions in the Body of the Corpus Callosum (BCC) and right Posterior Thalamic Radiation (PTR) regions relative to HCs, and FA reductions in the right PTR relative to NDS patients. NDS patients had FA reductions of the BCC and right PTR relative to HCs. Binomial logistic regression analyses revealed that FA reductions of the right PTR FA was an independent predictor of deficit status. The identified brain white matter changes especially in the PTR relate to deficits of cognitive control and emotional awareness, which may underlie psychopathology associated with deficit status like inattention and affective blunting. These potential biomarkers of DS warrant further examination to determine their utility for monitoring illness progression and intervention response in schizophrenia.

Altered Patterns of the Fractional Amplitude of Low-Frequency Fluctuation and Functional Connectivity Between Deficit and Non-Deficit Schizophrenia

Objective: A limited number of studies have previously reported on the regional activity [amplitude of low-frequency fluctuation (ALFF)] and functional integration [functional connectivity (FC)] of the whole brain in deficit schizophrenia (DS). The present study investigates the resting-state characteristics of the fractional ALFF (fALFF) and the FC in both DS and non-deficit schizophrenia (NDS) patients, and further explores their correlations with neurocognitive features. Methods: Demographic, resting-state functional magnetic resonance imaging (MRI), and neurocognitive data were collected from 33 DS and 41 NDS male patients, as well as in 40 male healthy controls (HCs). The voxel-wise fALFF was measured to evaluate regional cerebral function. Regions with differences in fALFF between DS and NDS patients were used as seed points in whole-brain FC analysis. Partial correlation analysis was conducted to examine associations between the fALFF or the FC of altered regions and neurocognitive assessments. Results: Both patient groups showed decreased fALFF in the sensorimotor area, visual cortex, and frontoparietal pathway, but increased fALFF in the precuneus and middle cingulate gyrus when compared with the HCs. Moreover, the NDS group demonstrated higher fALFF than HCs in the left thalamus, caudate, and hippocampus. Compared with the NDS group, the fALFF of the visual cortex was specifically increased, but that of the bilateral insula, the anterior cingulate gyrus (ACG), and the regions extended to the frontotemporal cortex was decreased in the DS group. Numerous abnormal FCs of nerve pathways were found between the two patient groups, mainly concentrated in the frontooccipital, frontotemporal, insula-visual cortex, as well as the temporooccipital pathway. Correlation analysis indicated that, in the DS group, the FC value between the left insula and the visual cortex was positively correlated with cognitive flexibility. In the NDS group, the fALFF of the right insula was negatively correlated with speech fluency, and the FC value between the ACG and the visual cortex was positively correlated with visual spatial memory. Conclusion: The present study demonstrates different altered patterns of fALFF and FC between male patients with DS and NDS. The specific altered regions of the salience network (SN) associated with impaired neurocognition in male DS patients suggest novel insights into the pathogenesis of cognitive impairment in schizophrenia.

Serum BDNF and GDNF in Chinese male patients with deficit schizophrenia and their relationships with neurocognitive dysfunction

BackgroundTo measure the serum levels of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) in deficit schizophrenia (DS), in order to examine the association between these two neurotrophic factors (NFs) and cognitive performance.MethodsA total of 109 male patients [51 DS and 58 non-deficit schizophrenia (NDS)] with schizophrenia and 40 sex and age matched healthy controls (HC) participated in this study. Processing speed, attention, executive function, and working memory of all subjects were assessed by means of a battery of classical neuropsychological tests. Serum BDNF and GDNF levels were measured simultaneously using a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA).ResultsThere were significant differences in the overall cognitive test scores between three groups (all p < 0.001). Serum BDNF levels were significantly lower in patients (DS and NDS) than in HC (p < 0.001). Furthermore, BDNF levels were lower in the DS compared to the NDS group, although not significantly. However, there was no difference in the GDNF levels between patients (DS and NDS) and HC. GDNF levels were positively correlated with scores of Stroop words only (r = 0.311, p = 0.033), Stroop colors only (r = 0.356, p = 0.014) and Stroop interference (r = 0.348, p = 0.016) in DS group.ConclusionSerum BDNF may be an unsuitable biomarker for DS, despite a significant decrease in schizophrenia patients. The different neurocognitive performance between the DS and NDS patients indicates that DS may be a separate clinical entity of schizophrenia. Finally, higher serum GDNF levels are associated with better cognitive performance in DS patients, indicating a possible neuroprotective function in DS.

Breakdown of the Paracellular Tight and Adherens Junctions in the Gut and Blood Brain Barrier and Damage to the Vascular Barrier in Patients with Deficit Schizophrenia.

Deficit schizophrenia is characterized by leaky intestinal tight and adherens junctions and bacterial translocation. Here we examine whether (deficit) schizophrenia is accompanied by leaky paracellular, transcellular, and vascular barriers in the gut and blood-brain barriers. We measured IgA responses to occludin, claudin-5, E-cadherin, and β-catenin (paracellular pathway, PARA); talin, actin, vinculin, and epithelial intermediate filament (transcellular pathway, TRANS); and plasmalemma vesicle-associated protein (PLVAP, vascular pathway) in 78 schizophrenia patients and 40 controls. IgA responses to claudin-5, E-cadherin, and β-catenin, the sum of the four PARA proteins, and the ratio PARA/TRANS were significantly higher in deficit schizophrenia patients than in nondeficit schizophrenia patients and controls. A large part of the variance in PHEMN (psychosis, hostility, excitation, mannerism, and negative) symptoms, psychomotor retardation, formal thought disorders, verbal fluency, word list memory, word list recall, and executive functions was explained by the PARA/TRANS ratio coupled with plasma IgA responses to Gram-negative bacteria, IgM to malondialdehyde, CCL-11 (eotaxin), IgA levels of the ratio of noxious to more protective tryptophan catabolites (NOX/PRO TRYCATs), and a plasma immune activation index. Moreover, IgA levels to Gram-negative bacteria were significantly associated with IgA to E-cadherin, β-catenin, and PLVAP, while IgA levels to claudin-5 were significantly predicted by IgA to E-cadherin, NOX/PRO TRYCAT ratio, Gram-negative bacteria, and CCL11. The phenomenology of the deficit syndrome is to a large extent explained by the cumulative effects of lowered natural IgM, breakdown of the paracellular and vascular pathways, increased bacterial translocation, peripheral immune-inflammatory responses, and indices of BBB breakdown.

Aberrant cerebellar neural activity and cerebro-cerebellar functional connectivity involving executive dysfunction in schizophrenia with primary negative symptoms.

Deficit schizophrenia (DS) is a distinct subtype of schizophrenia characterized by primary and enduring negative symptoms. More severe executive dysfunctions were observed in DS patients, however, the associated neuroimaging characteristics, especially cerebellar functional anomalies in DS, remain largely unknown. We employed resting-state functional and structural MRI data of 106 male participants, including data from 29 DS patients, 39 non-deficit schizophrenia (NDS) patients and 38 healthy controls (HCs). Z-standardized fractional amplitude of low-frequency fluctuation (zfALFF) values were calculated in order to examine spontaneous regional brain activity. Cerebro-cerebellar functional connectivity and changes in the volume of gray matter in the cerebellum were also examined. Relative to the HCs, both DS and NDS patients exhibited decreased zfALFF in the bilateral cerebellar lobules VIII and IX. The zfALFF in the left Crus II was lower in DS patients compared to NDS patients. No significant difference was observed in the volume of cerebellar gray matter among the three groups. Compared with NDS patients, cerebro-cerebellar functional connectivity analysis revealed increased connectivity in the left orbital medial frontal cortex and right putamen regions in DS patients. Reduced zfALFF in the left Crus II in the DS group was significantly positively correlated with Stroop Color and Word scores, while negatively correlated with Trail-Making Test part B scores. The increased functional connectivity in the right putamen in DS patients was significantly positively correlated with Animal Naming Test and semantic Verbal Fluency Test scores. These results highlight cerebellar functional abnormality in DS patients and provide insight into the pathophysiological mechanism of executive dysfunction.

DNA Methylation and Gene Expression of Matrix Metalloproteinase 9 Gene in Deficit and Non-deficit Schizophrenia.

The biological pathology of deficit schizophrenia (DS) remains unclear. Matrix metalloproteinase 9 (MMP9) might be associated with neural plasticity and glutamate regulation, involved in schizophrenia pathogenesis. This study explores gene expression and DNA methylation of MMP9 in peripheral blood mononuclear cells (PBMCs) and their relationship with clinical symptoms in DS and non-deficit schizophrenia (NDS). Pyrosequencing was used to determine DNA methylation at CpG sites in exon 4 and exon 5 of MMP9 in 51 DS patients, 53 NDS patients and 50 healthy subjects (HC). RT-qPCR was used to detect MMP9 expression. Clinical symptoms were assessed by BPRS, SANS and SAPS scales. MMP9 expression in PBMCs was significantly higher in DS than NDS and HC subjects. Compared to NDS patients, DS patients had significantly lower DNA methylation at individual CpG sites in exon 4 and exon 5 of MMP9. Correlation analysis showed that DNA methylation in exon 4 was negatively correlated with gene expression in DS group. Positive correlation was found between MMP9 expression and negative symptoms in total schizophrenic patients. The social amotivation factor of SANS and negative syndrome of BPRS was negatively correlated with DNA methylation of CpG5-1 in DS patients but not in NDS patients. DS patients showed a specific abnormality of peripheral MMP9 expression and DNA methylation, indicating a pathological mechanism underlying DS as a specific subgroup of schizophrenia.

Convergent and divergent altered patterns of default mode network in deficit and non-deficit schizophrenia

ObjectivePrevious studies suggested likely mechanisms underlying the dysfunction of the default mode network (DMN) in schizophrenia. However, altered patterns of the intrinsic activity of the DMN in both deficit schizophrenia (DS) and non-deficit schizophrenia (NDS) patients, as well as the neurocognitive relationships among them, remain unknown. This study explores the resting-state characteristics of the DMN activity in both DS and NDS patients, and further investigates correlations with neurocognitive features. MethodsDemographic, resting-state functional MRI, and neurocognitive data were collected in 37 DS and 38 NDS patients, as well as in 38 matched healthy control subjects (HCs). Independent component analysis was conducted to investigate the characteristics of DMN activity and to further distinguish between common and specific altered regions. In addition, partial correlation analysis was conducted to examine associations between the activity of altered regions and neurocognitive assessments. ResultsOverlapping altered brain activity was observed in both DS and NDS patients in the left middle frontal gyrus (MFG), the left angular gyrus (ANG), and the calcarine sulcus (CAL) region. Furthermore, compared to HCs, DS patients showed less activity in the right inferior temporal gyrus, the right para-hippocampal gyrus / hippocampus (PHP / HIP), and the left precuneus (PCUN), while they showed increased activity in the posterior cingulate cortex (PCC). Notably, NDS patients showed less activity in the bilateral middle occipital gyrus. Correlation analysis indicated that, in the DS group, both Trail Making Test (TMT)-B and spatial processing scores were positively associated with the activities of the left PCUN and the right PHP / HIP, while the Stroop color scores were negatively associated with PCC activity. In the NDS group, the TMT-B scores were associated with activities of the left MFG and CAL regions, while the scores of the Wechsler adult intelligence scale (Chinese revision) were negatively associated with CAL region activity. ConclusionThe present study demonstrates convergent and divergent altered patterns of the DMN in both DS and NDS patients. Importantly, the specific altered regions of the DMN in DS patients may be associated with extensive deficient neurocognition, indicating novel insights into the pathogenesis of cognitive impairment in schizophrenia.