Impairment In Schizophrenia Patients Research Articles

Association between angiotensin-converting enzyme gene insertion/deletion polymorphism and cognition impairment in patients with schizophrenia.

Several lines of evidence indicate that an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene (ACE) gene may be involved in the pathogenesis of schizophrenia and cognitive impairment. However, the relationship between ACE I/D polymorphism and cognitive impairment in patients with schizophrenia remains unclear. The aim of this study was to examine whether ACE gene I/D polymorphism contributed to cognitive impairment in Chinese patients with schizophrenia, and whether the association between clinical symptoms and cognitive impairment depended on different ACE genotypes. The ACE I/D polymorphism was genotyped in 928 schizophrenia patients and 325 healthy controls using a case-control design. The severity of psychopathological symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). Cognitive functioning was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). There were significant differences in genotype and allele frequencies of the ACE I/D polymorphism between patients and healthy controls (both P < 0.01). After controlling for demographic characteristics, patients who are homozygous carriers of D and I performed worse on the RBANS attention index than heterozygous carriers (P = 0.009). In addition, attention index score was negatively correlated with PANSS negative symptom score in patients of all genotypes (all P < 0.05), and positively correlated with positive symptom score only in the I/I genotype (P = 0.005). These findings suggest that ACE I/D gene variants play a role in susceptibility to schizophrenia, specific cognitive impairment and the association between clinical symptoms and cognitive impairment in schizophrenia patients.

Correlation Between Cortical Thickness Abnormalities of the Olfactory Sulcus and Olfactory Identification Disorder and Persistent Auditory Verbal Hallucinations in Chinese Patients With Chronic Schizophrenia.

Persistent auditory verbal hallucinations (pAVHs) and olfactory identification impairment are common in schizophrenia (SCZ), but the neuroimaging mechanisms underlying both pAVHs and olfactory identification impairment are unclear. This study aimed to investigate whether pAVHs and olfactory identification impairment in SCZ patients are associated with changes in cortical thickness. In this study, cortical thickness was investigated in 78 SCZ patients with pAVHs (pAVH group), 58 SCZ patients without AVHs (non-AVH group), and 83 healthy controls (HC group) using 3T magnetic resonance imaging. The severity of pAVHs was assessed by the Auditory Hallucination Rating Scale. Olfactory identification deficits were assessed using the Odor Stick Identification Test for Japanese (OSIT-J). In addition, the relationship between the severity of pAVHs and olfactory identification disorder and cortical thickness abnormalities was determined. Significant reductions in cortical thickness were observed in the right medial orbital sulcus (olfactory sulcus) and right orbital sulcus (H-shaped sulcus) in the pAVH group compared to both the non-AVH and HC groups (P < .003, Bonferroni correction). Furthermore, the severity of pAVHs was found to be negatively correlated with the reduction in cortical thickness in the olfactory sulcus and H-shaped sulcus. Additionally, a decrease in cortical thickness in the olfactory sulcus showed a positive correlation with the OSIT-J scores (P < .05, false discovery rate correction). Cortical thickness abnormalities in the olfactory sulcus may be a common neuroimaging mechanism for pAVHs and olfactory identification deficits in SCZ patients.

Altered mitochondrial lymphocyte in overweight schizophrenia patients treated with atypical antipsychotics and its association with cognitive function.

Increasing evidence indicated that schizophrenia and obesity are associated with altered mitochondrial and immune function. In this study, we investigated the levels of CRP (C-reactive protein) and mitochondrial lymphocytes in chronically treated schizophrenia patients with atypical antipsychotic medications and further explored the relationship between mitochondrial lymphocyte and weight gain as well as cognitive function in these patients. We evaluated the mitochondrial lymphocyte count of 97 patients (53 overweight, 44 non-overweight) and 100 healthy controls using mitochondrial fluorescence staining and flow cytometry (NovoCyte, Agilent Technologies, US). The serum CRP was measured by high-sensitivity enzyme-linked immunosorbent assay (ELISA). Clinical symptoms and cognitive function of the patients were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The results showed that mitochondrial lymphocyte counts of CD3+ T, CD3+CD4+ T, and CD3+CD8+ T cells in schizophrenia patients were higher than in the control group (p < 0.05). Additionally, overweight patients had significantly higher mitochondrial lymphocyte counts of CD3+ T and CD3+CD4+ T cells compared to schizophrenia patients with normal weight. Stratified analysis by gender revealed that there was a statistically significant difference in CD3+CD4+ mitochondrial lymphocyte count in male patients (p = 0.014) and a marginal trend toward significance in female patients (p = 0.058). Furthermore, the mitochondrial lymphocyte counts of CD3+ T and CD3+CD4+ T cells, as well as CRP levels, were positively correlated with BMI in schizophrenia patients, but the mitochondrial lymphocyte counts of CD3+CD4+ T cells were negatively correlated with the language scale in the RBANS. Our study results provide evidence for the association between altered mitochondrial T lymphocyte and weight gain as well as cognitive impairment in schizophrenia patients treated with atypical antipsychotic medications.

Aberrant hyperfocusing in schizophrenia indicated by elevated theta phase-gamma amplitude coupling

ObjectiveWe aimed to investigate electroencephalographic (EEG) markers of aberrant hyperfocusing, a novel framework of impaired selective attention, in schizophrenia patients by using theta phase-gamma amplitude coupling (TGC). MethodsFifty-four schizophrenia patients and 73 healthy controls (HCs) underwent EEG recording during an auditory oddball paradigm. For the standard and target conditions, TGC was calculated using the source signals from 25 brain regions of interest (ROIs) related to attention networks and sensory processing; TGC values were then compared across groups and conditions using two-way analysis of covariance. Correlations of altered TGC with performance on the Trail Making Test Parts A and B (TMT-A/B), were explored. ResultsCompared to HCs, schizophrenia patients showed elevated TGC in the left inferior frontal gyrus (IFG) and superior temporal gyrus in the standard condition but not in the target condition. Correlation analyses revealed that the TGC in the left IFG was positively correlated with the TMT-A/B completion times. ConclusionsAberrant hyperfocusing, as reflected by elevated TGC in attention-related brain regions, was related to behavioral performance on the TMT-A/B in schizophrenia patients. SignificanceThis study suggests that TGC is a electrophysiological marker for aberrant hyperfocusing of attentional processes that may result in cognitive impairments in schizophrenia patients.

FMRI fluctuations within the language network are correlated with severity of hallucinatory symptoms in schizophrenia

Although schizophrenia (SZ) represents a complex multiform psychiatric disorder, one of its most striking symptoms are auditory verbal hallucinations (AVH). While the neurophysiological origin of this pervasive symptom has been extensively studied, there is so far no consensus conclusion on the neural correlates of the vulnerability to hallucinate. With a network-based fMRI approach, following the hypothesis of altered hemispheric dominance (Crow, 1997), we expected that LN alterations might result in self-other distinction impairments in SZ patients, and lead to the distressing subjective experiences of hearing voices. We used the independent component analysis of resting-state fMRI data, to first analyze LN connectivity in three groups of participants: SZ patients with and without hallucinations (AVH/D+ and AVH/D–, respectively), and a matched healthy control (HC) group. Then, we assessed the fMRI fluctuations using additional analyses based on fractional Amplitude of Low Frequency-Fluctuations (fALFF), both at the network- and region of interest (ROI)-level. Specific LN nodes were recruited in the right hemisphere (insula and Broca homologous area) for AVH/D+ , but not for HC and AVH/D–, consistent with a left hemisphere deficit in AVH patients. The fALFF analysis at the ROI level showed a negative correlation between fALFF Slow-4 and P1 Delusions PANSS subscale and a positive correlation between the fALFF Slow-5 and P3 Hallucination PANSS subscale for AVH/D+ only. These effects were not a consequence of structural differences between groups, as morphometric analysis did not evidence any group differences. Given the role of language as an emerging property resulting from the integration of many high-level cognitive processes and the underlying cortical areas, our results suggest that LN features from fMRI connectivity and fluctuations can be a marker of neurophysiological features characterizing SZ patients depending on their vulnerability to hallucinate.

Metformin improves cognitive impairment in patients with schizophrenia: associated with enhanced functional connectivity of dorsolateral prefrontal cortex

Cognitive impairment is a core feature of schizophrenia, which is aggravated by antipsychotics-induced metabolic disturbance and lacks effective pharmacologic treatments in clinical practice. Our previous study demonstrated the efficiency of metformin in alleviating metabolic disturbance following antipsychotic administration. Here we report that metformin could ameliorate cognitive impairment and improve functional connectivity (FC) in prefrontal regions. This is an open-labeled, evaluator-blinded study. Clinically stable patients with schizophrenia were randomly assigned to receive antipsychotics plus metformin (N = 48) or antipsychotics alone (N = 24) for 24 weeks. The improvement in cognition was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Its association with metabolic measurements, and voxel-wise whole-brain FC with dorsolateral prefrontal cortex (DLPFC) subregions as seeds were evaluated. When compared to the antipsychotics alone group, the addition of metformin resulted in significantly greater improvements in the MCCB composite score, speed of processing, working memory, verbal learning, and visual learning. A significant time × group interaction effect of increased FC between DLPFC and the anterior cingulate cortex (ACC)/middle cingulate cortex (MCC), and between DLPFC subregions were observed after metformin treatment, which was positively correlated with MCCB cognitive performance. Furthermore, the FC between left DLPFC A9/46d to right ACC/MCC significantly mediated metformin-induced speed of processing improvement; the FC between left A46 to right ACC significantly mediated metformin-induced verbal learning improvement. Collectively, these findings demonstrate that metformin can improve cognitive impairments in schizophrenia patients and is partly related to the FC changes in the DLPFC. Trial Registration: The trial was registered with ClinicalTrials.gov (NCT03271866). The full trial protocol is provided in Supplementary Material.

10 Hz repetitive transcranial magnetic stimulation (rTMS) may improve cognitive function: An exploratory study of schizophrenia patients with auditory hallucinations

ObjectivesCognitive impairment in schizophrenia patients with auditory hallucinations is more prominent compared to those without. Our study aimed to investigate the cognitive improvement effects of 10 Hz repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) in schizophrenia with auditory hallucinations. MethodsA total of 60 schizophrenic patients with auditory hallucinations in this study were randomly assigned to sham or active group. Both groups received 10 Hz or sham rTMS targeted in left DLPFC for 20 sessions. The Positive and Negative Syndrome Scale (PANSS), the Auditory Hallucination Rating Scale (AHRS), the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and the Udvalg for Kliniske Under-sogelser (UKU) side effect scale were used to measure psychiatric symptoms, auditory hallucinations, cognition, and side reaction, respectively. ResultsOur results indicated that the active group experienced greater improvements in RBANS-total score (P = 0.043) and immediate memory subscale score (P = 0.001). Additionally, the PANSS-total score, negative and positive subscale score were obviously lower in the active group compared to the sham group (all P < 0.050). Furthermore, our study found that the improvement of RBANS-total score was positively associated with the decline of positive factor score, and the improvement of language score in RBANS was positively associated with the reduction in PANSS-total scale, negative and positive subscale score in the real stimulation group (all P < 0.050). ConclusionOur results demonstrated that a four-week intervention of 10 Hz rTMS over the left DLPFC can improve cognition (particularly immediate memory) among schizophrenia patients with auditory hallucinations. Future studies with larger sample size are needful to verify our preliminary findings.

The validity of a therapeutic invigoration task in avolitional schizophrenia outpatients.

Avolition is associated with much morbidity and functional impairment in schizophrenia patients. Vigor may be taken as, in part, the inverse of avolition, but it has not been investigated as a therapeutic pursuit before. To this end, a therapeutic invigoration task was developed drawing on cognitive-behavioral and guided imagery therapies. This study investigated the validity and reliability of a therapeutic invigoration task in avolitional residual phase schizophrenia outpatients. In a proof-of-concept quasi-experimental one-group sequentially repeated pretest/posttest study design, patients (n = 76) participated in a structured invigoration task that was repeated after 1 month (n = 70). Patients' vigor during the preceding 7 days measured on the Vigor Assessment Scale increased highly significantly in anticipation of the subsequent 7 days on both occasions with respectively very large (Cohen's δ with Hedges' correction [δ] = 1.46) and large (δ = 1.04) effect sizes. The anticipated vigor after the first occasion was partially consummated during the subsequent month in that vigor during the 7 days preceding the second occasion was lower than participants had anticipated but still significantly higher than at baseline (p < 0.001; δ = 0.70). Repeating the task a month later, together with homework, had a cumulative effect as indicated by a very large effect size (δ = 1.61). Results suggest that the invigoration task did what it was supposed do, and did so consistently, in patients with avolitional residual schizophrenia. These results warrant a subsequent randomized controlled trial to establish the efficacy of the invigoration task.

Sex difference in association between tardive dyskinesia and cognitive deficits in patients with chronic schizophrenia.

Tardive dyskinesia (TD), a side effect due to long-term use of antipsychotic medication, is associated with cognitive impairment. Several studies have found sex differences in cognitive impairment in schizophrenia patients, while whether there are sex differences in cognitive performance in schizophrenia patients with TD has not been reported. A total of 496 schizophrenia inpatients and 362 healthy controls were recruited for this study. We used the Positive and Negative Syndrome Scale (PANSS) to assess patients' psychopathological symptoms and the Abnormal Involuntary Movement Scale (AIMS) to assess the severity of TD. Cognitive function was measured in 313 of these inpatients and 310 of healthy controls using the Repeatable Battery for Assessment of Neuropsychological Status (RBANS). Patients with schizophrenia performed worse in all cognitive domains than healthy controls(all p<0.001). Compared to patients without TD, patients with TD had higher PANSS total, PANSS negative symptom subscale and AIMS scores (all p<0.001), while RBANS total, visuospatial/constructional and attention subscale scores were significantly lower (all p<0.05). In addition, the visuospatial/constructional and attention indices remained significantly lower in male patients with TD than those without TD (both p<0.05), but these results were not observed in female patients. Moreover, visuospatial/constructional and attention indices were negatively correlated with total AIMS scores only in male patients (both p<0.05). Our results suggest that there may be sex differences in cognitive impairment in schizophrenia patients with comorbid TD, indicating that female gender may have a protective effect on cognitive impairment in schizophrenia patients caused by TD.

Abnormalities of Regional Brain Activity in Patients With Schizophrenia: A Longitudinal Resting-State fMRI Study.

Evidence from functional and structural research suggests that abnormal brain activity plays an important role in the pathophysiology of schizophrenia (SZ). However, limited studies have focused on post-treatment changes, and current conclusions are inconsistent. We recruited 104 SZ patients to have resting-state functional magnetic resonance imaging scans at baseline and 8 weeks of treatment with second-generation antipsychotics, along with baseline scanning of 86 healthy controls (HCs) for comparison purposes. Individual regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF), and degree centrality values were calculated to evaluate the functional activity. The Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery were applied to measure psychiatric symptoms and cognitive impairment in SZ patients. Compared with HCs at baseline, SZ patients had higher ALFF and ReHo values in the bilateral inferior temporal gyrus, inferior frontal gyrus, and lower ALFF and ReHo values in fusiform gyrus and precuneus. Following 8 weeks of treatment, ReHo was increased in right medial region of the superior frontal gyrus (SFGmed) and decreased in the left middle occipital gyrus and the left postcentral gyrus. Meanwhile, ReHo of the right SFGmed was increased after treatment in the response group (the reduction rate of PANSS ≥50%). Enhanced ALFF in the dorsolateral of SFG correlated with improvement in depressive factor score. These findings provide novel evidence for the abnormal functional activity hypothesis of SZ, suggesting that abnormality of right SFGmed can be used as a biomarker of treatment response in SZ.

Alcohol related cognitive impairments in schizophrenia patients : A case-control study

IntroductionCognitive impairment is a well-recognized key feature of schizophrenia. However, these cognitive impairments may be worsened by alcohol consumption. Up to 80% of patients with alcohol use disorders (AUD) display cognitive impairments. Screening for those impairments with a full neuropsychological assessment may be difficult. The Brief Evaluation Alcohol-Related Neuropsychological Impairments (BEARNI) is a specific tool for screening those impairments easy to implement in in clinical practice (Ritz et al. Alcoholism: Clinical and Experimental Research 2015; 39, 2249-60). To our knowledge, no previous studies have assessed the alcohol-related cognitive impairments using the BEARNI test in schizophrenia patients.ObjectivesThe objective of the study was to compare BEARNI mean scores between a group of schizophrenia patients with alcohol use disorders and a group of schizophrenia patients without alcohol use disorder.Methods39 patients with schizophrenia and AUD (SCZ/AUD +) (82% males, mean age 44.9 ± 11.0 years-old) and 49 patients with schizophrenia without AUD (SCZ/AUD-) (65% males, mean age 42.6 ± 11.4 years-old) consecutively included in the study, were assessed using the BEARNI test. All patients met DSM-5 criteria for schizophrenia and AUD. Demographic and clinical variables were also collected, using the Alcohol Use Disorders Identification Test (AUDIT) and the Positive and Negative Syndrome Scale (PANSS). The primary endpoint of the study was the difference in BEARNI cognitive mean scores between the SCZ/AUD+ and SCZ/AUD- groups.ResultsThere was no difference between the two groups regarding demographic variables or PANSS mean scores (59.1 ± 12.8 vs 58.1 ± 14.0; t=-0.3; p=0.7). The AUDIT mean score was higher in the group of patients SCZ/AUD+ (20.6 ± 7.8 vs 1.6 ± 1.5; t=-14.7; p&lt;0.0001). Total BEARNI and cognitive BEARNI mean scores were significantly lower in the group of patients SCZ/AUD+ compared to the group of patients SCZ/AUD- (10.6 ± 4.8 vs 12.6 ± 5.2; t=1.8, p=0.03 and 8.1 ± 3.9 vs 9.8 ± 3.6 t=2.0, p=0.04, respectively). The mean subscores of delayed verbal memory, alphabetical ordination, and alternating verbal fluency subtests were also significantly lower in the group of patients SCZ/+ group (respectively 1,0 ± 0.9 vs 1.6 ± 1.2, t= 2.5, p=0.01; 2,1 ± 1.2 vs 2.5 ± 1.1, t= 1.6, p=0.04; 3.3 ±1.5 vs 3.8 ± 1.5, t= 1.8, p=0.03).ConclusionsThe present study found cognitive impairments using BEARNI test in schizophrenia patients with AUD compared to their counterparts without AUD. Screening alcohol related cognitive impairments using BEARNI could be easier in patients in schizophrenia patients with AUD than usual neurocognitive assessmentsDisclosure of InterestNone Declared

Cognitive Rehabilitation in Schizophrenia-Associated Cognitive Impairment: A Review

Patients suffering from schizophrenia often experience cognitive disturbances. Cognitive rehabilitation-computerized or non-computerized-is widely known as an alternative way to enhance cognitive functioning in patients with schizophrenia. The aim of the present review was to examine the role of cognitive rehabilitation (both computerized and non-computerized) for the alleviation of cognitive impairment in schizophrenia patients. Fourteen relative studies were examined and included in the present review. The results revealed that both computerized and non-computerized cognitive rehabilitation could enhance cognitive functioning and more specifically memory, attention, executive functioning, processing speed and in a few cases, even non-cognitive impairments, such as other schizophrenia symptoms. The present results support the efficacy of cognitive rehabilitation in schizophrenia patients, regardless of whether it is computerized or non-computerized. As the randomized control trials (RCTs) are limited in number, there is urgent need for more RCTs and longitudinal studies combining different kinds of interventions, as well as systematic reviews and meta-analyses, in order to further investigate and confirm the current results.

Protective Effects of Shi-Zhen-An-Shen Decoction on the Cognitive Impairment in MK801-Induced Schizophrenia Model.

Cognitive dysfunction is a core feature of schizophrenia that strongly correlates to the patients' difficulties in independent living and occupational functioning. Synaptic dysfunction may result in cognitive and behavioral changes similar to what have been identified in schizophrenia. Shi-Zhen-An-Shen Decoction (SZASD) is the empirical formula of traditional Chinese medicine adopted in treating psychiatric symptoms, especially the cognitive impairment in schizophrenia patients, with proven efficacy in the long term of clinical practice in Beijing Anding Hospital, Capital Medical University. However, the mechanisms of SZASD on the cognitive improvement in schizophrenia is still unclear. Here, we aim to investigate the underlying mechanisms of the impact of SZASD on the cognitive impairment in MK801-induced schizophrenia-like rats. Six rat groups (n = 12 per group) were subjected to different treatments for 14 days. All the six groups were injected intraperitoneally with a given volume of 0.9% saline and MK801 (0.2 mg/kg) for consecutive 14 days for modelling. And the rats in the SZASD-treated groups and the clozapine-treated group were given SZASD (low, middle, and high doses) or clozapine, respectively, by intragastric administration. Then, we performed behavioral tests after the treatments, and the rats were sacrificed on the 19th day for biological analysis. Behavioral tests indicated that SZASD mitigated the aberrant motor activity and improved schizophrenia-like rats' spatial reference memory and sensory gating ability. Furthermore, SZASD significantly increased the expressions of PSD95, BDNF, and synapsin I in the hippocampus of MK801-induced schizophrenia-like rats. Our findings suggest that SZASD may ameliorate cognitive impairment by restoring the levels of synaptic proteins in the hippocampus.

Alterations of cerebellar white matter integrity and associations with cognitive impairments in schizophrenia.

“Cognitive dysmetria” theory of schizophrenia (SZ) has highlighted that the cerebellum plays a critical role in understanding the pathogenesis and cognitive impairment in SZ. Despite some studies have reported the structural disruption of the cerebellum in SZ using whole brain approach, specific focus on the voxel-wise changes of cerebellar WM microstructure and its associations with cognition impairments in SZ were less investigated. To further explore the voxel-wise structural disruption of the cerebellum in SZ, the present study comprehensively examined volume and diffusion features of cerebellar white matter in SZ at the voxel level (42 SZ vs. 52 controls) and correlated the observed alterations with the cognitive impairments measured by MATRICS Consensus Cognitive Battery. Combing voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) methods, we found, compared to healthy controls (HCs), SZ patients did not show significant alteration in voxel-level cerebellar white matter (WM) volume and tract-wise and skeletonized DTI features. In voxel-wise DTI features of cerebellar peduncles, compared to HCs, SZ patients showed decreased fractional anisotropy and increased radial diffusivity mainly located in left middle cerebellar peduncles (MCP) and inferior cerebellar peduncles (ICP). Interestingly, these alterations were correlated with overall composite and different cognitive domain (including processing speed, working memory, and attention vigilance) in HCs but not in SZ patients. The present findings suggested that the voxel-wise WM integrity analysis might be a more sensitive way to investigate the cerebellar structural abnormalities in SZ patients. Correlation results suggested that inferior and MCP may be a crucial neurobiological substrate of cognition impairments in SZ, thus adding the evidence for taking the cerebellum as a novel therapeutic target for cognitive impairments in SZ patients.

The inconsistent mediating effect of catechol O methyl transferase Val158Met polymorphism on the sex difference of cognitive impairment in schizophrenia patients.

ObjectiveSchizophrenia is a multifaceted mental disorder characterized by heterogeneous positive/negative symptoms and cognitive deficits. Sex differences have been reported in various aspects of the disease. However, the underlying genetic reasons remain unelucidated. Recent studies show that the influence of COMT Val158Met (rs4680) variation is sexually dimorphic. Thus, this study aims to explore whether there is an effect of the interaction between COMT Val158Met (rs4680) polymorphism and sex on patients’ clinical characteristics and cognitive function.Materials and methodsWe recruited 367 in patients with chronic schizophrenia (246 males and 121 females) and 419 healthy controls (172 males and 247 females). The cognitive performance was assessed by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and the COMT Val158Met (rs4680) polymorphism is genotyped. The psychopathological symptoms of the patients were assessed by the Positive and Negative Syndrome Scale (PANSS).ResultsWe find that male patients had a significantly higher proportion of carrying the Val allele and Val/Val carriers exhibited more severe positive symptoms and cognitive impairment than Met carriers. COMT Val158Met (rs4680) polymorphism inconsistently mediated the relationship between sex and cognitive performance in schizophrenia patients.ConclusionThese findings suggest that COMT Val158Met (rs4680) polymorphism is associated with the risk and severity of schizophrenia in a sexually dimorphic way and contributes more to the clinical symptoms and cognitive impairment in male patients with schizophrenia.

Characterizing serum amino acids in schizophrenic patients: Correlations with gut microbes

Amino acid abnormalities have been suggested to be a key pathophysiological mechanism in schizophrenia (SZ). Recently, gut microbes were found to be critically involved in mental and metabolic diseases. However, the relationship between serum amino acid levels and gut microbes in SZ is rarely studied. Here, we analyzed serum amino acid levels in 76 untreated SZ patients and 79 healthy controls (HC). Serum levels of 10 amino acids were significantly altered in patients with SZ. We further classified the cut-off values for serum arginine, leucine, glutamine, and methionine levels to distinguish SZ patients from controls. These classifiers were shown to be effective in another validation cohort (49 SZ and 48 HC). The correlation between serum amino acids and clinical symptoms and cognitive functions was also analyzed. Arginine, leucine, glutamine, and methionine levels were significantly correlated with clinical symptoms and cognitive impairments in SZ patients. By metagenome shotgun sequencing of fecal samples, we found that patients with SZ with a low level of serum amino acids have higher richness and evenness of the gut microbiota. At the genus level, the abundances of Mitsuokella and Oscillibacter are significantly abnormal. At the mOTU level, 15 mOTUs in the low-level SZ group were significantly different from the HC group. In addition, Mitsuokella multacida was correlated with glutamine and methionine, respectively. Our research revealed that alterations in serum amino acid levels are critically related to changes in gut microbiota composition in SZ patients. These findings may shed light on new strategies for the diagnosis and treatment of SZ.

Correlation of BDNF, VEGF, TNF‐α, and S100B with cognitive impairments in chronic, medicated schizophrenia patients

Cognitive impairment is a prominent cause of disability in schizophrenia. Although antipsychotic drugs can rescue the psychotic symptoms, the cognitive impairments persist, with no treatment available. Alterations of BDNF, VEGF, TNF‐α, and S100B have been linked to cognitive impairment in several neurological disorders. However, it remains unclear whether their levels are correlated with the cognitive functions of schizophrenia patients. Forty‐one chronic, medicated schizophrenia patients were included in this study. Enzyme‐linked, immunosorbent assays were used to measure the serum concentrations of BDNF, VEGF, TNF‐α, and S100B. Associations between serum protein levels and various domains of the cognitive functions of the schizophrenia patients were observed. We found significant, positive correlations between serum BDNF and the processing speed and attention levels of the patients. Serum VEGF was also positively correlated with their memory and learning functions. In contrast, serum S100B and TNF‐α were negatively correlated with the processing speed and attention of the schizophrenia patients. The findings warrant further investigation of these molecules as potential prognostic markers or treatment targets for cognitive impairment in schizophrenia patients.

The Predictive Role of Aberrant Metabolic Parameters and Negative Automatic Thinking on the Cognitive Impairments Among Schizophrenia Patients with Metabolic Syndrome

PurposeThe study aimed to clarify the cognitive impairments of schizophrenia with metabolic syndrome while evaluating their potential as risk factors.Patients and MethodsWe recruited 153 participants and divided them into three groups according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria and the guideline standards for the prevention and treatment of dyslipidemia in Chinese adults in 2007 for metabolic syndrome, as follows: healthy control group (n = 47); nonmetabolic syndrome group (n = 58); and metabolic syndrome group (n = 48). Psychotic symptoms were evaluated using the Positive and Negative Syndrome Scale. Cognitive function and automatic thinking were estimated using the Montreal Cognitive Assessment Scale, Verbal Fluency Test, and Automatic Thoughts Questionnaire. Serum biochemical parameters were measured by automatic biochemistry analyzer.ResultsOne-way ANOVA analysis revealed that differential cognition impairments in schizophrenia patients compared to controls. Furthermore, results of multiple comparisons showed that more serious barriers in orientation, language fluency, and negative automatic thinking existed in the metabolic syndrome group than in the healthy and non-metabolic syndrome groups. Spearman correlation and stepwise linear regression analyses showed that psychopathological symptoms, high waist circumference, and high triglyceride were the predictive factors for negative automatic thoughts, orientation, and language fluency. Those results collectively revealed that high waist circumference, high triglyceride and negative automatic thinking had validity and effectiveness in predicting the cognitive function impairments of the metabolic syndrome group.ConclusionThe present findings strongly supported the notion that aberrant parameters of high waist circumference, high triglyceride and high negative automatic thoughts had validity and effectiveness predictive role for cognitive impairments in the schizophrenics with metabolic syndrome. The schizophrenia patients with metabolic syndrome should receive regular monitoring and adequate treatment for metabolic and psychological risk factors.

Selective impairment of timing in a NMDA hypofunction animal model of psychosis

Schizophrenia is severe neuropsychiatric disease, which is commonly accompanied not only by positive or negative symptoms, but also by cognitive impairment. To study neuronal mechanisms underlying cognitive distortions and mechanisms underlying schizophrenia, animal pharmacological models of cognitive symptoms are commonly used. Between various cognitive impairments in schizophrenia patients, disturbed time perception has often been reported. Here, we examined temporal and spatial cognition in a modified Carousel maze task in the animal model of schizophrenia induced by non-competitive NMDA-receptor antagonists MK-801. Male Long-Evans rats (n = 18) first learned to avoid the aversive sector on a rotating arena in both dark and light intervals. We verified that during dark, rats used temporal cues, while during light they relied predominantly on spatial cues. We demonstrated that the timing strategy depends on the stable rotation speed of the arena and on the repositioning clues such as aversive stimuli. During testing (both in light and dark intervals), half of the rats received MK-801 and the control half received saline solution. We observed dose-dependent disruptions of both temporal and spatial cognition. Namely, both doses of MK-801 (0.1 and 0.12 mg/kg) significantly impaired timing strategy in the dark and increased locomotor activity. MK-801 dose 0.1 mg/kg, but not 0.12, also impaired spatial avoidance strategy in light. We found that the timing strategy is more sensitive to NMDA antagonist MK-801 than the spatial strategy. To conclude, a modified version of the Carousel maze is a useful and sensitive tool for detecting timing impairments in the MK-801 induced rodent model of schizophrenia.

Sex differences in the association between serum BDNF and cognitive impairment in schizophrenia patients using various antipsychotics

BackgroundCognitive impairment is one of the core symptoms of schizophrenia patients. There are often various differences in the efficacy of different antipsychotics in the treatment of cognitive impairment by sex. The purpose of this study was to explore whether there are gender differences in the association between serum BDNF levels and cognitive performance in patients with schizophrenia taking different antipsychotics. MethodsWe used Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to assess the cognitive function of three groups of schizophrenia patients (420 on clozapine, 183 on risperidone, 215 on typical antipsychotic drugs) and 467 healthy controls. Positive and Negative Syndrome Scale (PANSS) was used to assess schizophrenia symptoms of patients. Enzyme-Linked ImmunoSorbent Assay was used to measure serum brain-derived neurotrophic factor (BDNF) levels. ResultsAmong the patients taking clozapine and typical antipsychotic drugs, the RBANS total score, immediate memory, attention, and delayed memory subscores in females were higher than those in males (all p < 0.05). The RBANS total score and the delayed memory subscores in female patients taking risperidone were higher than those in male patients (all p < 0.05). Significant correlation between BDNF and cognition only existed in male patients taking clozapine, male patients taking risperidone, and male and female patients taking typical antipsychotic drugs (all p < 0.05). ConclusionRegardless of antipsychotic effect, the cognitive function of female patients is better compared to that of male patients. For male patients, the association between BDNF and cognitive performance exists in each medication group. For female patients, this significant association was only shown in the typical antipsychotic group, but not in the clozapine and risperidone groups.