Changes in Inflammatory Biomarkers in Patients with Schizophrenia: A 3-Year Retrospective Study.

Objective: Accumulating evidence suggested that immune system activation might be involved in the pathophysiology of schizophrenia. The neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), platelet/lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) can measure inflammation. This study aimed to investigate the inflammatory state in patients with schizophrenia by using these indicators. Methods: In this study, the complete blood count data for 187 continuing hospitalized patients with schizophrenia and 187 age- and sex-matched healthy participants was collected annually from 2017 to 2019. Platelet (PLT), lymphocyte (LYM), monocyte (MON) and neutrophil (NEU) counts were aggregated and NLR, MLR, PLR, and SII were calculated. Using a generalized linear mixed model, we assessed the impact of age, sex, diagnosis, and sampling year on the above indicators and evaluated the interaction between the factors. Results: According to the estimation results of the generalized linear mixed model, the NLR increased by 0.319 (p = 0.004), the MLR increased by 0.037 (p < 0.001), and the SII increased by 57.858 (p = 0.018) in patients with schizophrenia. Data after two years of continuous antipsychotic treatment showed that the NLR and MLR were higher in patients with schizophrenia than those in healthy controls, while the PLT and LYM counts were decreased in patients with schizophrenia. The schizophrenia diagnosis was correlated to the MON and LYM count, NLR, MLR, and SII (p < 0.05). Conclusion: The differences in these markers were stable and cannot be eliminated by a full course of treatment. This study provides impetus for the inflammatory hypothesis of schizophrenia.

Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia: randomized trials and multiomics analysis.

BACKGROUND: Choosing the appropriate antipsychotic drug (APD) treatment for patients with schizophrenia (SCZ) can be challenging, as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers. Previous studies have indicated the association between treatment response and genetic and epigenetic factors, but no effective biomarkers have been identified. Hence, further research is imperative to enhance precision medicine in SCZ treatment. METHODS: Participants with SCZ were recruited from two randomized trials. The discovery cohort was recruited from the CAPOC trial (n = 2307) involved 6 weeks of treatment and equally randomized the participants to the Olanzapine, Risperidone, Quetiapine, Aripiprazole, Ziprasidone, and Haloperidol/Perphenazine (subsequently equally assigned to one or the other) groups. The external validation cohort was recruited from the CAPEC trial (n = 1379), which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine, Risperidone, and Aripiprazole groups. Additionally, healthy controls (n = 275) from the local community were utilized as a genetic/epigenetic reference. The genetic and epigenetic (DNA methylation) risks of SCZ were assessed using the polygenic risk score (PRS) and polymethylation score, respectively. The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis, methylation quantitative trait loci, colocalization, and promoter-anchored chromatin interaction. Machine learning was used to develop a prediction model for treatment response, which was evaluated for accuracy and clinical benefit using the area under curve (AUC) for classification, R2 for regression, and decision curve analysis. RESULTS: Six risk genes for SCZ (LINC01795, DDHD2, SBNO1, KCNG2, SEMA7A, and RUFY1) involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response. The developed and externally validated prediction model, which incorporated clinical information, PRS, genetic risk score (GRS), and proxy methylation level (proxyDNAm), demonstrated positive benefits for a wide range of patients receiving different APDs, regardless of sex [discovery cohort: AUC = 0.874 (95% CI 0.867-0.881), R2 = 0.478; external validation cohort: AUC = 0.851 (95% CI 0.841-0.861), R2 = 0.507]. CONCLUSIONS: This study presents a promising precision medicine approach to evaluate treatment response, which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ. Trial registration Chinese Clinical Trial Registry ( https://www.chictr.org.cn/ ), 18. Aug 2009 retrospectively registered: CAPOC-ChiCTR-RNC-09000521 ( https://www.chictr.org.cn/showproj.aspx?proj=9014 ), CAPEC-ChiCTR-RNC-09000522 ( https://www.chictr.org.cn/showproj.aspx?proj=9013 ).

Measuring Sleep Stages and Screening for Obstructive Sleep Apnea with a Wearable Multi-Sensor System in Comparison to Polysomnography.

Objective: To assess the performance of a wearable multi-sensor system (SensEcho) in comparison to polysomnography (PSG) in measuring sleep stages and searching for obstructive sleep apnea (OSA). Methods: Participants underwent overnight simultaneous monitoring using SensEcho and PSG in a sleep laboratory. SensEcho analyzed the recordings spontaneously, and PSG was assessed as per standard guidelines. The degree of snoring was evaluated according to the guidelines for the diagnosis and treatment of OSA hypopnea syndrome (2011 revision). The Epworth Sleepiness Scale (ESS) was used to assess general daytime sleepiness. Results: This study included 103 Han Chinese, 91 of whom (age 39.02 ± 13.84 years, body mass index 27.28 ± 5.12 kg/m2, 61.54% male) completed the assessments. The measures of total sleep time (P = 0.198); total wake time (P = 0.182); shallow sleep (P = 0.297), deep sleep (P = 0.422), rapid eye movement sleep (P = 0.570), and awake (P = 0.336) proportions were similar between SensEcho and PSG. Using an apnea-hypopnea index (AHI) cutoff of ≥ 5 events/h, the SensEcho had 82.69% sensitivity and 89.74% specificity. Almost the same results were obtained at an AHI threshold of ≥ 15 events/h. Although the specificity increased to 94.67%, it decreased to 43.75% at an AHI cutoff of ≥ 30 events/h. Conclusion: This study demonstrated that SensEcho can be used to evaluate sleep status and screen for OSA. Nevertheless, improving the accuracy of its assessment of severe OSA and further testing its effectiveness in community and home environments is necessary.

Vocal acoustic features may be objective biomarkers of negative symptoms in schizophrenia: A cross-sectional study.

BACKGROUND: There are currently no objective biomarkers that allow the quantification of negative symptoms of schizophrenia. This study therefore explored the use of acoustic features in identifying the severity of negative symptoms in patients with schizophrenia. METHODS: We recruited 79 inpatients who were diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (the schizophrenia group) at the Huilongguan Hospital in Beijing, China, and 79 healthy controls from the surrounding community (the control group). We assessed the clinical symptoms of the patients with schizophrenia using the Positive and Negative Syndrome Scale (PANSS) and the Brief Negative Symptom Scale (BNSS) and recorded the voice of each participant as they read emotionally positive, neutral, and negative texts. The Praat software was used to analyse and extract acoustic characteristics from the recordings, such as jitter, shimmer, and pitch. The acoustic differences between the two groups of participants and the relationship between acoustic characteristics and clinical symptoms in the patient group were analysed. RESULTS: There were significant differences between the schizophrenia and control groups in pitch, voice breaks, jitter, shimmer, and the mean harmonics-to-noise ratio (p < 0.05). Jitter was negatively correlated with the blunted affect and alogia subscale scores of the BNSS, both in the positive and neutral emotion conditions, but the correlation disappeared in the negative emotion condition. However, shimmer exhibited a stable negative correlation with the blunted affect and alogia subscale scores of the BNSS in all three emotion conditions. A linear regression analysis showed that pitch, jitter, shimmer, and age were statistically significant predictors of BNSS subscale scores. CONCLUSIONS: Acoustic emotional expression differs between patients with schizophrenia and healthy controls. Some acoustic characteristics are related to the severity of negative symptoms, regardless of semantic emotions, and may therefore be objective biomarkers of negative symptoms. A systematic method for assessing vocal acoustic characteristics could provide an accurate and feasible means of assessing negative symptoms in schizophrenia. TWEET: Acoustic emotional expression differs between patients with schizophrenia and healthy controls. A systematic method for assessing vocal acoustics could provide an accurate and feasible means of assessing negative symptoms in schizophrenia.

Vocal Acoustic Features as Potential Biomarkers for Identifying/Diagnosing Depression: A Cross-Sectional Study.

Background: At present, there is no established biomarker for the diagnosis of depression. Meanwhile, studies show that acoustic features convey emotional information. Therefore, this study explored differences in acoustic characteristics between depressed patients and healthy individuals to investigate whether these characteristics can identify depression. Methods: Participants included 71 patients diagnosed with depression from a regional hospital in Beijing, China, and 62 normal controls from within the greater community. We assessed the clinical symptoms of depression of all participants using the Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Patient Health Questionnaire (PHQ-9), and recorded the voice of each participant as they read positive, neutral, and negative texts. OpenSMILE was used to analyze their voice acoustics and extract acoustic characteristics from the recordings. Results: There were significant differences between the depression and control groups in all acoustic characteristics (p < 0.05). Several mel-frequency cepstral coefficients (MFCCs), including MFCC2, MFCC3, MFCC8, and MFCC9, differed significantly between different emotion tasks; MFCC4 and MFCC7 correlated positively with PHQ-9 scores, and correlations were stable in all emotion tasks. The zero-crossing rate in positive emotion correlated positively with HAMA total score and HAMA somatic anxiety score (r = 0.31, r = 0.34, respectively), and MFCC9 of neutral emotion correlated negatively with HAMD anxiety/somatization scores (r = -0.34). Linear regression showed that the MFCC7-negative was predictive on the PHQ-9 score (ß = 0.90, p = 0.01) and MFCC9-neutral was predictive on HAMD anxiety/somatization score (ß = -0.45, p = 0.049). Logistic regression showed a superior discriminant effect, with a discrimination accuracy of 89.66%. Conclusion: The acoustic expression of emotion among patients with depression differs from that of normal controls. Some acoustic characteristics are related to the severity of depressive symptoms and may be objective biomarkers of depression. A systematic method of assessing vocal acoustic characteristics could provide an accurate and discreet means of screening for depression; this method may be used instead of-or in conjunction with-traditional screening methods, as it is not subject to the limitations associated with self-reported assessments wherein subjects may be inclined to provide socially acceptable responses rather than being truthful.

TGF-ß1 is associated with deficits in cognition and cerebral cortical thickness in first-episode schizophrenia.

BACKGROUND: Evidence indicates that cytokines are associated with cognitive deficits in schizophrenia; however, the underlying brain-behaviour mechanisms remain unclear. We hypothesized that aberrations in brain structural connectivity mediate the cytokine effect in schizophrenia. METHODS: In this study, we recruited patients with first-episode schizophrenia (n = 75, average illness duration 12.3 months, average medication period 0.6 days) and healthy controls (n = 44) of both sexes. We first conducted whole-blood RNA sequencing to detect differentially expressed genes. We also explored transcriptomic data on the dorsal lateral prefrontal cortices (dlPFC) retrieved from the CommonMind Consortium for gene functional clustering; we measured plasma transforming growth factor ß1 (TGF-ß1) levels by enzyme-linked immunosorbent assay; we acquired high-resolution T 1-weighted MRI data on cortical thickness MRI; and we assessed cognitive function using the validated Chinese version of the MATRICS Consensus Cognitive Battery. We compared these parameters in patients with schizophrenia and controls, and analyzed their associations. RESULTS: Patients with schizophrenia had higher TGF-ß1 at both the mRNA level (log2 fold change = 0.24; adjusted p = 0.026) and the protein level (12.85 ± 6.01 µg/mL v. 8.46 ± 5.15 µg/mL, adjusted p < 0.001) compared to controls. Genes coexpressed with TGFB1 in the dlPFC were less abundant in patients with schizophrenia compared to healthy controls. In patients with schizophrenia, TGF-ß1 protein levels were inversely correlated with cortical thickness, especially of the lateral occipital cortex (r = -0.47, adjusted p = 0.001), and with the MATRICS Consensus Cognitive Battery visual learning and memory domain (r = -0.50, adjusted p < 0.001). We found a complete mediation effect of the thickness of the lateral occipital cortex on the negative relationship between TGF-ß1 and visual cognition (p < 0.05). LIMITATIONS: We did not explore the effect of other blood cytokines on neurocognitive performance and cortical thickness. Participants from the CommonMind Consortium did not all have first-episode schizophrenia and they were not all antipsychotic-naive, so we could not exclude an effect of antipsychotics on TGF-ß1 signalling in the dlPFC. The sample size and cross-sectional design of our study were additional limitations. CONCLUSION: These findings highlighted an association between upregulated blood levels of TGF-ß1 and impairments in brain structure and function in schizophrenia.

Association of serum uric acid levels with suicide risk in female patients with major depressive disorder: a comparative cross-sectional study.

BACKGROUND: Individuals with major depressive disorder (MDD) have a high suicide risk. Some evidence suggests that uric acid (UA) may be involved in the pathophysiology of MDD. The purpose of this study was to evaluate whether serum UA levels were associated with suicide risk in MDD patients. METHODS: One hundred four female patients with MDD (52 patients with suicide risk and 52 patients without suicide risk) and 52 healthy individuals were included in this study. The suicide risk was evaluated by Mini International Neuropsychiatric Interview (M.I.N.I.). Fasting serum levels of UA, as well as glucose, lipid and renal function indicators were measured. RESULTS: Serum UA levels in MDD patients with suicide risk (245.01 ± 55.44 µmol/L) were significantly lower than those in MDD patients without suicide risk (274.17 ± 72.65 µmol/L) (p = 0.017) and healthy controls (271.42 ± 55.25 µmol/L) (p = 0.030). There was no difference in serum UA levels between the MDD patients without suicide risk and healthy controls (p = 0.821). Binary logistic regression analysis revealed a significant relationship between suicide risk and decreased serum UA levels (OR = 0.989, p = 0.010) in MDD patients. CONCLUSION: Decreased serum UA levels were associated with suicide risk in MDD patients. Purinergic system dysfunction may be involved in the neurobiological basis of suicide risk in these patients.

The Effect of Cognitive Impairment on the Prognosis of Major Depressive Disorder.

The study recruited 168 patients diagnosed with major depressive disorder (MDD). The nine-item Patient Health Questionnaire (PHQ-9) and Perceived Deficits Questionnaire for Depression (PDQ-D) were lower and the Digit Symbol Substitution Test (DSST) was higher in the community volunteers than those in MDD patients. Depression-related scores (17-item Hamilton Depression Rating Scale [HAMD-17], Clinical Global Impressions-Severity of Illness Scale [CGI-S], and PHQ-9), functioning-related scores (Sheehan Disability Scale [SDS]), and Work Efficiency and Activity Damage-Specific Health Problems questionnaire work productivity loss were decreased, and the quality of life-related scores (European Quality of life-5 Dimensions [EQ-5D] utility score) were increased in the MDD patients. PDQ-D was decreased and DSST was increased with the increase of follow-up time. Linear regression indicated that cognitive symptoms (PDQ-D and DSST) improved more slowly than depressive symptoms (PHQ-9). At baseline, PDQ-D was related with functioning (SDS and work productivity loss). PDQ-D and DSST were related with EQ-5D utility score. In addition, at month 6, PDQ-D was related with functioning (SDS and work productivity loss) and EQ-5D utility score. Cognitive impairment might be a risk for MDD and MDD-related changes in the functioning and quality of life.

Choroid Plexus Enlargement and Allostatic Load in Schizophrenia.

Although schizophrenia is a brain disorder, increasing evidence suggests that there may be body-wide involvement in this illness. However, direct evidence of brain structures involved in the presumed peripheral-central interaction in schizophrenia is still unclear. Seventy-nine previously treatment-naïve first-episode schizophrenia patients who were within 2-week antipsychotics initial stabilization, and 41 age- and sex-matched healthy controls were enrolled in the study. Group differences in subcortical brain regional structures measured by MRI and the subclinical cardiovascular, metabolic, immune, and neuroendocrine biomarkers as indexed by allostatic load, and their associations were explored. Compared with controls, patients with schizophrenia had significantly higher allostatic load (P = .001). Lateral ventricle (P < .001), choroid plexus (P < .001), and thalamus volumes (P < .001) were significantly larger, whereas amygdala volume (P = .001) was significantly smaller in patients. The choroid plexus alone was significantly correlated with higher allostatic load after age, sex, education level, and the total intracranial volume were taken into account (t = 3.60, P < .001). Allostatic load was also significantly correlated with PANSS positive (r = 0.28, P = .016) and negative (r = -0.31, P = .008) symptoms, but in opposite directions. The peripheral multisystemic and central nervous system abnormalities in schizophrenia may interact through the choroid plexus during the early stage of the illness. The choroid plexus might provide a sensitive structural biomarker to study the treatment and prevention of brain-periphery interaction abnormalities in schizophrenia.

Microglial regional heterogeneity and its role in the brain.

Microglia have been recently shown to manifest a very interesting phenotypical heterogeneity across different regions in the mammalian central nervous system (CNS). However, the underlying mechanism and functional meaning of this phenomenon are currently unclear. Baseline diversities of adult microglia in their cell number, cellular and subcellular structures, molecular signature as well as relevant functions have been discovered. But recent transcriptomic studies using bulk RNAseq and single-cell RNAseq have produced conflicting results on region-specific signatures of microglia. It is highly speculative whether such spatial heterogeneity contributes to varying sensitivities of individual microglia to the same physiological and pathological signals in different CNS regions, and hence underlie their functional relevance for CNS disease development. This review aims to thoroughly summarize up-to-date knowledge on this specific topic and provide some insights on the potential underlying mechanisms, starting from microgliogenesis. Understanding regional heterogeneity of microglia in the context of their diverse neighboring neurons and other glia may provide an important clue for future development of innovative therapies for neuropsychiatric disorders.

Patients With Drug-Naive Bipolar Disorder in Remission After 8 Weeks of Treatment Had Decreased Serum Uric Acid Concentrations.

Background: Evidence indicates that the serum concentration of uric acid (UA) in patients may relate both to the pathophysiology and therapeutics of bipolar disorder (BPD). The purpose of this study was to examine the changes and clinical significance of serum UA concentrations in first-episode manic patients suffering from BPD. Methods: Seventy-six drug-naive patients with first-episode bipolar mania and 76 age- and gender-matched healthy subjects were recruited. Young Mania Rating Scale and Hamilton Depression Rating Scale were used to assess clinical symptoms. We tested serum UA concentrations by sandwich enzyme-linked immunosorbent assay at baseline and at the end of 8-week treatment in BPD patients and in the control group. Results: After 8-week quetiapine and sodium valproate treatment, this study revealed that the serum UA concentrations in remitted patients were significantly lower than nonremitted patients; however, those remitted patients still had higher serum UA than healthy controls. We discovered that the baseline UA concentration was higher in nonremitted than remitted patients after 8 weeks of treatment. Finally, a positive association was found between serum UA and symptom relief in the first episode of manic disorder patients. Conclusion: Patients with first-episode BPD had high levels of serum UA, which responds to treatment mainly in remitted patients. Our results suggest that serum UA concentrations might present potentially a trait marker in bipolar patients.

Brain Abnormalities in Different Phases of Working Memory in Schizophrenia: An Integrative Multi-Modal MRI Study.

The current study aimed to examine both gray matter and functional activity changes in schizophrenia by combing both structural and task-related functional magnetic resonance imaging (fMRI). Nineteen patients with schizophrenia and 17 controls were recruited. The fMRI scan was performed while performing a working memory (WM) task. In terms of task performance, accuracy did not differ between groups, but there were significant differences in reaction time. Compared with controls, patients exhibited decreased functional activation in prefrontal areas, insula, lingual gyrus, and superior temporal gyrus during different phases of WM. The subcallosal cortex showed increased activation. Intriguingly, a structural-functional correlation was found in the left dorsolateral prefrontal cortex, anterior cingulate cortex, and subcallosal cortex in patients when performing high-load WM task. This study demonstrated both impaired gray matter volume and functional activation during WM in schizophrenia, suggesting structural and functional impairments. The structural-functional correlation in schizophrenia suggested that structural damage in schizophrenia might induce a decreased ability to modulate functional response in accordance with increasing task difficulty.

Interaction of BDNF and cytokines in executive dysfunction in patients with chronic schizophrenia.

Multiple lines of evidence indicate that patients with chronic schizophrenia (SCZ) display executive dysfunction across the illness course. However, the potential molecular pathophysiologic mechanisms remain poorly elucidated. Neurodevelopmental changes caused by alterations of inflammatory mediators and neurotrophins have been shown to occur in the earliest stages of SCZ, and be associated with executive dysfunction (ED) in SCZ. Therefore, the current study was to investigate whether the interplay between BDNF and inflammatory mediators was involved in the disruption of executive function of long-term hospitalized patients with chronic SCZ. Serum cytokines and BDNF levels were measured in 112 long-term hospitalized patients with chronic SCZ and 44 healthy normal controls. Executive functions were assessed by verbal fluency tests (VFT), the Stroop word-color test (Stroop), and the Wisconsin card sorting tests (WCST).The results showed that the patients had higher IL-2, IL-6, IL-8, but lower TNF-α and BDNF compared to control subjects. In the patient group, BDNF was positively associated with IL-2 and IL-8 levels, while lower BDNF levels were correlated with ED measured by VFT and WCST tests. Multiple stepwise regression analyses confirmed that BDNF × IL-8 and BDNF × TNF-α were factors influencing the total score of VFT, while BDNF × IL-8 and BDNF × TNF-α were recognized as influencing factors for WCST scores. Our results suggest complex interactions between BDNF and cytokines were involved in the pathophysiology of executive function impairments in patients with SCZ.

More dampened monocytic Toll-like receptor 4 response to lipopolysaccharide and its association with cognitive function in Chinese Han first-episode patients with schizophrenia.

OBJECTIVE: Accumulating evidence suggests alterations of the innate immune system are related to schizophrenia, although the precise mechanism remains to be elucidated. In this study, we aimed to detect the monocytic toll-like receptor 4 (TLR4) expression under basal and lipopolysaccharide (LPS)-stimulated conditions in first-episode (FE) Han Chinese patients with schizophrenia, as well as its association with cognitive function. METHODS: Whole blood samples were taken in 42 FE schizophrenia patients and 36 healthy controls. Expressions of TLR4 on monocytes under basal and LPS-stimulated conditions were measured with flow cytometry. Psychopathological symptoms of schizophrenia were assessed by the Positive and Negative Syndrome Scale (PANSS) and the MATRICS Consensus Cognitive Battery (MCCB) was administered to all of the participants. RESULTS: We found no differences in percentage and mean fluorescence intensity (MFI) of TLR4 expression on monocytes between patients and controls at basal status. However, LPS challenge resulted in a lower cell-surface level of TLR4 on monocytes in FE schizophrenia patients as compared to healthy controls (TLR4+%: F = 4.092, p = 0.047; TLR4 + MFI: F = 4.820, p = 0.031). In addition, correlation analysis together with multivariate linear regression analysis identified basal percentage of TLR4 in monocytes as the beneficial factor for visual learning and working memory in FE patients with schizophrenia. CONCLUSIONS: Our findings suggested that TLR4 may be involved in the pathophysiology of schizophrenia, corroborating the role of innate immunity-related functional deficits in increased risk of schizophrenia.

Fluoxetine induces lipid metabolism abnormalities by acting on the liver in patients and mice with depression.

Depressive disorders are frequently managed with long-term use of antidepressant medication. Fluoxetine (FLX) is the first selective serotonin reuptake inhibitor to be widely available for the treatment of depression. The present study focuses on the effects and mechanisms of the lipid metabolism abnormalities caused by FLX in patients and in a mouse model of depression. Depression severity was assessed by the Hamilton Depression Scale (HAMD). Triglyceride (TG), cholesterol (TC) and low-density lipoprotein (LDL) serum levels were assessed in 28 patients with depression, aged 31.2±3.3 years, treated with FLX (20 to 60 mg/day) for 8 weeks. Meanwhile, the serum levels of other lipid metabolism-related parameters, such as high-density lipoprotein (HDL), apolipoprotein A1 (APOA1) and apolipoprotein B (ApoB), were also determined. The infiuence of FLX on the hepatic lipid profile and hepatic gene expression of both lipogenic and lipolytic enzymes was evaluated in a mouse model of depression treated with FLX (10 mg·kg-1·d-1, ip) for 4 weeks. We showed that the serum TG, TC and LDL levels were significantly increased in patients with depression after FLX treatment. The elevation in serum TG levels in the patients was not affected by gender or family history. FLX treatment did not significantly alter serum HDL, APOA1 or APOB levels in the patients. We further demonstrated in mice with depression that FLX treatment increased the hepatic TG level by increasing the expression of lipogenic enzymes and decreasing the expression of lipolytic enzymes in the liver. Antidepressive therapy with FLX is associated with lipid metabolism abnormalities, which are in part mediated by disturbances in hepatic lipid metabolism homeostasis. The findings contribute to the uncovering of metabolic adverse reactions in the pharmacological therapy of depression.

Tumor necrosis factor-alpha -1031T/C polymorphism is associated with cognitive deficits in chronic schizophrenia patients versus healthy controls.

Recent compelling research has demonstrated a pathophysiologic role for proinflammatory cytokines of microglial origin in decreasing neurocognitive function. Psychiatric diseases are already known to have reduced cognitive function and are also associated with increased inflammation. To elaborate on these data, our study aims to investigate how a particular polymorphism of the tumor necrosis factor gene, TNF-α -1031T/C, affects neurocognitive performance in patients with schizophrenia. We recruited 905 patients with schizophrenia and 571 healthy control subjects. We employed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to test for neurocognitive function and the positive and negative syndrome scale to evaluate schizophrenia severity. The -1031T/C polymorphism was genotyped in both healthy controls and schizophrenic patients. Our results demonstrate that patients with the C allele (either T/C or C/C) possessed increased immediate memory index, visuospatial/constructional index, and RBANS total scores as compared to patients without it (p < .05). In healthy controls, there was no significant difference across genotypes (p > .05). Our findings demonstrate that the TNF-α -1031T/C polymorphism may not play a role in the susceptibility of schizophrenia itself, but may be involved in the cognitive deficits of schizophrenia. This suggests an important role for cytokine signaling in mediating the severity of cognitive dysfunction in schizophrenia.

Interleukin-3, symptoms and cognitive deficits in first-episode drug-naïve and chronic medicated schizophrenia.

Previous studies consistently showed that IL-3 signaling may be involved in the pathophysiology of schizophrenia. However, investigations of associations between IL-3 and the neurocognitive impairments are lacking, including the study of how this may vary with stage of illness. We recruited 45 first-episode drug-naïve (FE-Sz), 35 chronic medicated schizophrenia (Ch-Sz) and 40 healthy controls (HC) and examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum IL-3. Altered serum IL-3 levels were found in both patient groups compared with HC group (both p < 0.001). There were significantly lower neurocognitive scores on the RBANS and nearly all of its five subscales, except for Visuospatial/Constructional index in both FE-Sz and Ch-Sz patients vs healthy controls. Moreover, a significant reduction in Immediate memory index (p = 0.021) and a trend-level reduction in RBANS total score (p = 0.094) in Ch-Sz than FE-Sz patients. Interestingly, there was a significant negative correlation between IL-3 and the Immediate memory index only in Ch-Sz patients (p = 0.03). Our findings showed that neurocognitive impairments present in schizophrenia emerge during the first episode with further diminished functioning with disease progression, and IL-3 may be involved in the immediate memory deficits in the chronic phase of schizophrenia.

P50 suppression deficits and psychopathology in Han Chinese patients with schizophrenia.

OBJECTIVE: Numerous studies have reported P50 gating deficits in schizophrenia, though with mixed results. Moreover, few studies have explored the association between P50 gating deficits and psychopathology in Chinese patients with schizophrenia. In the present study, we investigated the P50 auditory sensory gating patterns and their correlations with clinical symptoms in a large sample of Han Chinese patients with schizophrenia. METHODS: We assessed P50 sensory gating with a 64-channel electroencephalography system in 133 patients with schizophrenia and 148 healthy controls. The schizophrenia symptomatology was assessed with the Positive and Negative Syndrome Scale (PANSS). RESULTS: Patients with schizophrenia had a significantly higher P50 gating ratio (p<0.001), longer S1 latency (p<0.05), lower S1 amplitude (p<0.01), and lower P50 difference (p<0.001) than did controls. No significant correlations were found between the P50 gating measures and the PANSS total score or subscale scores in patients with schizophrenia. CONCLUSIONS: These findings suggest that the P50 sensory gating deficits identified in Chinese patients with schizophrenia may not be involved in the psychopathology of the illness.

Treatment satisfaction with paliperidone extended-release tablets: open-label study in schizophrenia patients dissatisfied with previous antipsychotic medication.

OBJECTIVE: The aim of this study was to evaluate the changes in treatment satisfaction after switching to paliperidone extended-release (ER) in Chinese schizophrenia patients dissatisfied with their previous antipsychotic treatment. METHODS: In this 8-week, open-label, single-arm, multicenter, prospective study, 1,693 patients dissatisfied with previous antipsychotic medication were enrolled and switched to paliperidone ER tablets (3-12 mg/d) based on clinical judgment. The primary efficacy end point was change in Medication Satisfaction Questionnaire (MSQ) score from baseline to week 8. The secondary end points included percentage of patients with MSQ score ≥4, as well as changes in Clinical Global Improvement-Severity (CGI-S) and Personal and Social Performance (PSP) scores. RESULTS: MSQ scores increased significantly from baseline (mean [standard deviation {SD}]: 2.48 [0.55]) to week 8 (5.47 [0.89], P<0.0001; primary end point, full analysis set). The percentage of patients with MSQ score ≥4 was 95.9% at week 8, indicating that most of the patients were satisfied with their treatment. Significant (P<0.0001) improvements from baseline to week 8 were noted in CGI-S score (2.37 [1.20]) and PSP score (25.5 [15.0]). A total of 174 (10.28%) patients experienced adverse events (AEs). The most common (>10 patients) events were extrapyramidal disorder (n=84, 4.96%), poor quality sleep (n=18, 1.06%) and akathisia (n=13, 0.77%). The majority of AEs were mild to moderate in severity. No deaths occurred. CONCLUSION: Treatment satisfaction improved after switching to paliperidone ER from the previous antipsychotic in Chinese patients with schizophrenia.

Ginkgo biloba leaf extract and alpha-tocopherol attenuate haloperidol-induced orofacial dyskinesia in rats: Possible implication of antiapoptotic mechanisms by preventing Bcl-2 decrease and Bax elevation.

BACKGROUND: Tardive dyskinesia (TD) is a serious side effect of long-term administration of typical neuroleptics, such as haloperidol. The pathophysiology of TD remains unclear, but the experimental evidence suggests that free radical-induced neuronal apoptosis in the basal ganglia may play an important role. PURPOSE: This study was to investigate changes in Bax and Bcl-2 expression levels in TD-associated brain regions and the effects of the antioxidant EGb761 on Bax and Bcl-2 levels in an animal model of TD. METHODS: Thirty-two rats were randomly divided into four study groups: saline control (saline), haloperidol-alone (haloperidol), EGb761-haloperidol (EGb), and alpha-tocopherol-haloperidol (vitamin E). Rats were treated with daily intraperitoneal haloperidol injections (2 mg/kg/day) for 5 weeks. EGb761 (50 mg/kg/day) and alpha-tocopherol (20 mg/kg/day) were then administered for another 5 weeks during the withdrawal period. Behavioral assessments were performed, and Bax and Bcl-2 protein expression levels were immunohistochemically analyzed in four brain regions, including the prefrontal cortex, striatum, substantia nigra, and globus pallidum. RESULTS: We found that increased vacuous chewing movements (VCMs) were associated with increased proapoptotic Bax protein expression, decreased antiapoptotic Bcl-2 protein expression, and an increased Bax/Bcl-2 ratio. EGb761 and alpha-tocopherol treatment reversed the increase in VCMs, decreased Bax expression, increased Bcl-2 expression, and decreased the Bax/Bcl-2 ratio. CONCLUSIONS: These results demonstrate that long-term haloperidol administration may affect Bcl-2 protein family expression and promote neuronal apoptosis in the basal ganglia. In combination with their antioxidant capacity, EGb761 and alpha-tocopherol's antiapoptotic effects through Bcl-2 might account for the symptom improvement observed in haloperidol-induced TD rats.