The classical D1 dopamine receptor antagonist SCH23390 is a functional sigma-1 receptor allosteric modulator.

SCH23390 is a widely used D1 dopamine receptor (D1R) antagonist that also elicits some D1R-independent effects. We previously found that the benzazepine, SKF83959, an analog of SCH23390, produces positive allosteric modulation of the Sigma-1 receptor (Sig1R). SCH23390 does not bind to the orthodoxic site of Sig1R but enhances the binding of 3H (+)-pentazocine to Sig1R. In this study, we investigated whether SCH23390 functions as an allosteric modulator of Sig1R. We detected increased Sig1R dissociation from binding immunoglobulin protein (BiP) and translocation of Sig1R to the plasma membrane in response to SCH23390 in transfected HEK293T and SH-SY5Y cells, respectively. Activation of Sig1R by SCH23390 was further confirmed by inhibition of GSK3ß activity in a time- and dose-dependent manner; this effect was blocked by pretreatment with the Sig1R antagonist, BD1047, and by knockdown of Sig1R. SCH23390 also inhibited GSK3ß in wild-type mice but not in Sig1R knockout mice. Finally, we showed that SCH23390 allosterically modulated the effect of the Sig1R agonist SKF10047 on inhibition of GSK3ß. This positive allosteric effect of SCH23390 was further confirmed via promotion of neuronal protection afforded by SKF10047 in primary cortical neurons challenged with MPP+. These results provide the first evidence that SCH23390 elicits functional allosteric modulation of Sig1R. Our findings not only reveal novel pharmacological effects of SCH23390 but also indicate a potential mechanism for SCH23390-mediated D1R-independent effects. Therefore, attention should be paid to these Sig1R-mediated effects when explaining pharmacological responses to SCH23390.

Interactions between overweight/obesity and alcohol dependence impact human brain white matter microstructure: evidence from DTI.

There is inconsistent evidence for an association of obesity with white matter microstructural alterations. Such inconsistent findings may be related to the cumulative effects of obesity and alcohol dependence. This study aimed to investigate the possible interactions between alcohol dependence and overweight/obesity on white matter microstructure in the human brain. A total of 60 inpatients with alcohol dependence during early abstinence (44 normal weight and 16 overweight/obese) and 65 controls (42 normal weight and 23 overweight/obese) were included. The diffusion tensor imaging (DTI) measures [fractional anisotropy (FA) and radial diffusivity (RD)] of the white matter microstructure were compared between groups. We observed significant interactive effects between alcohol dependence and overweight/obesity on DTI measures in several tracts. The DTI measures were not significantly different between the overweight/obese and normal-weight groups (although widespread trends of increased FA and decreased RD were observed) among controls. However, among the alcohol-dependent patients, the overweight/obese group had widespread reductions in FA and widespread increases in RD, most of which significantly differed from the normal-weight group; among those with overweight/obesity, the alcohol-dependent group had widespread reductions in FA and widespread increases in RD, most of which were significantly different from the control group. This study found significant interactive effects between overweight/obesity and alcohol dependence on white matter microstructure, indicating that these two controllable factors may synergistically impact white matter microstructure and disrupt structural connectivity in the human brain.

Aberrant degree centrality profiles during rumination in major depressive disorder.

Rumination is closely linked to the onset and maintenance of major depressive disorder (MDD). Prior neuroimaging studies have identified the association between self-reported rumination trait and the functional coupling among a network of brain regions using resting-state functional magnetic resonance imaging (MRI). However, little is known about the underlying neural circuitry mechanism during active rumination in MDD. Degree centrality (DC) is a simple metric to denote network integration, which is critical for higher-order psychological processes such as rumination. During an MRI scan, individuals with MDD (N = 45) and healthy controls (HC, N = 46) completed a rumination state task. We examined the interaction effect between the group (MDD vs. HC) and condition (rumination vs. distraction) on vertex-wise DC. We further characterized the identified brain region's functional involvement with Neurosynth and BrainMap. Network-wise seed-based functional connectivity (FC) analysis was also conducted for the identified region of interest. Finally, exploratory correlation analysis was conducted between the identified region of interest's network FCs and self-reported in-scanner affect levels. We found that a left superior frontal gyrus (SFG) region, generally overlapped with the frontal eye field, showed a significant interaction effect. Further analysis revealed its involvement with executive functions. FCs between this region, the frontoparietal, and the dorsal attention network (DAN) also showed significant interaction effects. Furthermore, its FC to DAN during distraction showed a marginally significant negative association with in-scanner affect level at the baseline. Our results implicated an essential role of the left SFG in the rumination's underlying neural circuitry mechanism in MDD and provided novel evidence for the conceptualization of rumination in terms of impaired executive control.

Multivariate classification based on large-scale brain networks during early abstinence predicted lapse among male detoxified alcohol-dependent patients.

Identifying biomarkers to predict lapse of alcohol-dependence (AD) is essential for treatment and prevention strategies, but remains remarkably challenging. With an aim to identify neuroimaging features for predicting AD lapse, 66 male AD patients during early-abstinence (baseline) after hospitalized detoxification underwent resting-state functional magnetic resonance imaging and were then followed-up for 6 months. The relevance-vector-machine (RVM) analysis on baseline large-scale brain networks yielded an elegant model for differentiating relapsing patients (n = 38) from abstainers, with the area under the curve of 0.912 and the accuracy by leave-one-out cross-validation of 0.833. This model captured key information about neuro-connectome biomarkers for predicting AD lapse.

Factors that contribute to trait mindfulness level among hospitalized patients with major depressive disorder.

Mindfulness training among patients with major depressive disorder (MDD) reduces symptoms, prevents relapse, improves prognosis, and is more efficient for those with a high level of trait mindfulness. Upon hospital admission, 126 MDD patients completed the Beck Depression Inventory (BDI), World Health Organization Quality of Life Brief, Five-Factor Mindfulness Questionnaire (FFMQ), and the Rumination Response Scale (RRS). The 65 patients that scored less than the median of all subjects on the FFMQ were placed into the low mindfulness level (LML) group. The other 61 patients were placed in the high mindfulness level (HML) group. All facet scores were statistically different between the mental health assessment scores of the HML and LML groups except for RRS brooding and FFMQ nonjudgement. Trait mindfulness level exhibited a negative and bidirectional association with MDD severity primarily through the facets of description and aware actions. Trait mindfulness was also related positively with age primarily through the facets of nonreactivity and nonjudgement. Being married is positively associated with trait mindfulness levels primarily through the facet of observation and by an associated increase in perceived quality of life. Mindfulness training prior to MDD diagnosis also associates positively with trait mindfulness level. Hospitalized MDD patients should have their trait mindfulness levels characterized to predict treatment efficiency, help establish a prognosis, and identify mindfulness-related therapeutic targets.

Delayed improvements in visual memory task performance among chronic schizophrenia patients after high-frequency repetitive transcranial magnetic stimulation.

BACKGROUND: Cognitive impairments are core characteristics of schizophrenia, but are largely resistant to current treatments. Several recent studies have shown that high-frequency repetitive transcranial magnetic stimulation (rTMS) of the left dor-solateral prefrontal cortex (DLPFC) can reduce negative symptoms and improve certain cognitive deficits in schizophrenia patients. However, results are inconsistent across studies. AIM: To examine if high-frequency rTMS of the DLPFC can improve visual memory deficits in patients with schizophrenia. METHODS: Forty-seven chronic schizophrenia patients with severe negative symptoms on stable treatment regimens were randomly assigned to receive active rTMS to the DLPFC (n = 25) or sham stimulation (n = 22) on weekdays for four consecutive weeks. Patients performed the pattern recognition memory (PRM) task from the Cambridge Neuropsychological Test Automated Battery at baseline, at the end of rTMS treatment (week 4), and 4 wk after rTMS treatment (week 8). Clinical symptoms were also measured at these same time points using the Scale for the Assessment of Negative Symptoms (SANS) and the Positive and Negative Syndrome Scale (PANSS). RESULTS: There were no significant differences in PRM performance metrics, SANS total score, SANS subscores, PANSS total score, and PANSS subscores between active and sham rTMS groups at the end of the 4-wk treatment period, but PRM performance metrics (percent correct and number correct) and changes in these metrics from baseline were significantly greater in the active rTMS group at week 8 compared to the sham group (all P < 0.05). Active rTMS treatment also significantly reduced SANS score at week 8 compared to sham treatment. Moreover, the improvement in visual memory was correlated with the reduction in negative symptoms at week 8. In contrast, there were no between-group differences in PANSS total score and subscale scores at either week 4 or week 8 (all P > 0.05). CONCLUSION: High-frequency transcranial magnetic stimulation improves visual memory and reduces negative symptoms in schizophrenia, but these effects are delayed, potentially due to the requirement for extensive neuroplastic changes within DLPFC networks.

Abnormal Brain Structure Morphology in Early-Onset Schizophrenia.

With less exposure to environmental and medication influences, individuals with early-onset schizophrenia (EOS) may provide valuable evidence to study the pathogenesis and phenotypic pattern of schizophrenia.T1-weighted magnetic resonance images were collected in 60 individuals with EOS and 40 healthy controls. Voxel-based morphometry and surface-based morphometry analyzes were performed. Gray matter volume, cortical thickness and cortical surface area were compared between the EOS and healthy controls and among schizophrenia subgroups (with or without family history of schizophrenia). Compared with healthy controls, the EOS group had reduced gray matter volume in the bilateral middle temporal gyrus and reduced cortical thickness in several brain regions. The sporadic early onset schizophrenia and the familial early onset schizophrenia showed different brain structure morphology. These findings suggest that abnormal brain structure morphology, especially in the temporal and frontal lobes, may be an important pathophysiological feature of EOS.

Correlation between reduced telomere length and behavioural and emotional problems in left-behind children in a rural area in China.

Evidence shows that being left behind experience (LBE) during childhood may increase the risks of poor psychopathological outcomes. However, it is unclear to what extent the mental health is affected by the LBE. Telomere length (TL), one of the most extensively studied biological markers of cellular ageing, provides a valuable tool for exploring the potential effects of parent-child separation on psychological problems by integrating genetic and environmental factors. In this study, a total of 613 children (mean age = 10.77, SD = 1.92) were recruited from the rural area of Deyang, Sichuan Province, China. We used a self-designed questionnaire to assess LBE, and collected psychopathological outcomes by using the Piers-Harris Children's Self-concept Scale, the Teacher's Report Form 6/18 and the Youth Self-Report 11/18. Terminal restriction fragment analysis was used to measure TL in peripheral blood leukocytes. Analyses revealed that 342 out of 613 participants (55.79%) were Left-behind children. LBE was observed to associated with shorter TL, lower self-esteem, and increased behavioural and emotional problems. The cumulative effects of LBE may be reflected by greater altered telomere homeostasis, decreased self-esteem, and worsened behavioural and emotional problems. The association of the total time of being left behind with self-esteem and behavioural and emotional problems was significantly mediated by altered telomere homeostasis, with estimated effects of 14.19%, 47.95% and 45.13%, respectively. The LBE in childhood, especially prolonged parent-child separation, increases the risk of mental health problems in childhood and adolescence.

Data-driven study on resting-state functional magnetic resonance imaging during early abstinence of alcohol dependence in male patients and its predictive value for relapse.

BACKGROUND: Alcohol dependence is a mental disorder with a high relapse rate. However, specific neuroimaging biomarkers have not been determined for alcohol dependence and its relapse. We conducted data-driven research to investigate resting-state functional magnetic resonance imaging (rs-fMRI) during early abstinence from alcohol dependence and its potential ability to predict relapse. METHODS: Participants included 68 alcohol-dependent patients and 68 healthy controls (HCs). The regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFF) were compared between the alcohol dependence group and the HCs and between the relapse group and the nonrelapse group. The brain regions that presented significantly different ReHo and/or fALFF between the alcohol-dependent patients and HCs and/or between the relapsed and nonrelapsed patients were selected as the seeds to calculate the functional connectivities (FCs). RESULTS: During a 6-month follow-up period, 52.24% of alcohol-dependent patients relapsed. A regression model for differentiating alcohol-dependent patients and HCs showed that reductions in ReHo in the left postcentral region, fALFF in the right fusiform region, and FC in the right fusiform region to the right middle cingulum were independently associated with alcohol dependence, with an area under the receiver operating characteristic curve (AUC) of 0.841. The baseline FC of the left precentral to the left cerebellum of the relapse group was significantly lower than that of the nonrelapse group. The AUC of this FC to predict relapse was 0.774. CONCLUSIONS: Our findings contribute to advancing research on the neurobiological etiology and predictive biomarkers for relapse associated with alcohol dependence.

A bidirectional association between internet addiction and depression: A large-sample longitudinal study among Chinese university students.

BACKGROUND: Internet addiction (IA) is associated with adverse consequences, especially for younger people. Evidence indicates that IA is associated with depression, but no studies have yet investigated potential common vulnerability between them. METHODS: IA (measured by the Young's 20-item Internet Addiction Test Scale) and depressive symptoms (measured by the Patient Health Questionnaire-9 Scale) among 12 043 undergraduates were surveyed at baseline and at a respective 12 month follow-up for each participant. Application of a cross-lagged panel model approach (CLPM) revealed an association between IA and depression after adjusting for demographic variables. RESULTS: Rates of baseline IA and depression were 5.47% (95% CI: 5.07%, 5.88%) and 3.85% (95% CI: 3.51%, 4.20%), respectively; increasing to 9.47% (95% CI: 8.94%, 9.99%) and 5.58% (95% CI: 5.17%,5.99%), respectively, at follow-up. Rates of new-incidences of IA and depression over 12 months were 7.43% (95% CI: 6.95%, 7.91%) and 4.47% (95% CI: 4.09%, 4.84%), respectively. Models in the present analysis revealed that baseline depression had a significant net-predictive effect on follow-up IA, and baseline IA had a significant net-predictive effect on follow-up depression. LIMITATIONS: The follow-up survey response rate was moderate (54.69%) in this analysis of university students. Moreover, the IAT-20 scale did not allow differentiate between specific forms of Internet activity. CONCLUSIONS: Common vulnerability and bidirectional cross-causal effects may both contribute to the association between IA and depression, with common vulnerability likely playing a more significant role than cross-causal effects.

Baseline beliefs about medication are associated with outcomes of antidepressants in inpatients with first-diagnosed depression under supervised therapeutic compliance.

The aim of the present study was to explore the effect of baseline beliefs about medication on therapeutic outcomes of antidepressants in inpatients with first-diagnosed depression under supervised therapeutic compliance. Ninety-seven inpatients with first-diagnosed depression were included to collect their baseline demographic data to evaluate the Hamilton depression rating scale (HAMD) scores and the beliefs about medicine questionnaire-specific (BMQ-S) scores at baseline and the end of the eight-week treatment. Additionally, we explored the relationship between inpatients' medication beliefs and therapeutic effect of antidepressants. The inpatients were divided into remitted depression and unremitted depression groups according to outcomes at the end of the eight-week treatment. There was no significant difference in the baseline HAMD between the two groups (P > 0.050). The scores on the BMQ-S of the unremitted group were significantly lower than those of the remitted group (P < 0.001). The HAMD scores were significantly reduced in both groups after the eight-week treatment (P < 0.001). There was no significant difference in the BMQ-S scores before and after the treatment (P > 0.050). The medication beliefs of the unremitted inpatients after the treatment were still lower than those of the remitted inpatients (P < 0.001). Logistic-regression analysis showed that low BMQ-S scores at the baseline were an independent risk factor for antidepressant efficacy. Beliefs about medication at baseline may be correlated with the therapeutic efficacy in inpatients with first-diagnosed depression under supervised therapeutic compliance.

[Animal Experimental Study of the Role of Menthol and Cineole, Two Tobacco Additives, on Nicotine Dependence].

OBJECTIVE: To establish a nicotine intravenous self-administration rat model, and to examine, with this model, the effects of two flavoring additives, menthol and cineole, on nicotine dependence. METHODS: Thirty male Sprague-Dawley (SD) rats were included in the study. After jugular venous catheterization was performed, fixed concentration of nicotine was administered in order to train the rats and establish the rat model of intravenous self-administration groups, receiving intraperitoneal injection of menthol, cineole, and dimethyl sulfoxide (DMSO), the vehicle that was used for the control group. The rats were tested with different fixed-ratio (FR) schedules, including FR1 schedule, in which the rat received one nicotine infusion for every active nose poke, FR2 schedule, in which the rat received one nicotine infusion for every two active nose pokes, and FR5 schedule, in which the rat received one nicotine infusion for every five active nose pokes. The number of active and inactive poke responses and the number of nicotine infusion were documented accordingly. RESULTS: After 10 days of training in nicotine self-administration, the 30 rats demonstrated significant increase in the number of active poke responses and the number of nicotine infusion, which were maintained at a stable and relatively high level. The number of active poke responses was significantly higher that of inactive poke responses ( P< 0.001). The rat model of intravenous nicotine self-administration was successfully established. In the testing phase, under the FR2 schedule, the menthol group showed a reduced number of active poke responses ( P=0.020). Under the FR5 schedule, the groups showed obvious interaction between time and the number of active poke responses ( P<0.011), with the menthol group showing reduced number of active poke responses on day three ( P=0.011) and the cineole group showing rising number of active poke responses on day three ( P=0.003). The DMSO control group did not show any significant change. CONCLUSIONS: Menthol and cineole are shown to have an effect on nicotine dependence. When there is relative difficulty involved in obtaining nicotine, menthol suppresses nicotine dependence, whereas cineole enhances nicotine dependence.

The interactions between childhood adversities and recent stress were associated with early-adulthood depression among Chinese undergraduate students.

BACKGROUND: It is widely acknowledged that childhood adversities (CAs) and recent stress are potential risk factors for adult depression. However, the mechanism(s) by which interactions of CAs with recent stress affect adult depression remain unclear. AIMS: To investigate the predictive association of the interaction among CAs and recent stress with early-adult depression. METHOD: We conducted an annual survey of all freshmen for the period of 2016-2018 in a Chinese comprehensive university, with a sample size of 23,206. An online questionnaire including standardized self-report instruments was used to assess sociodemographic factors, childhood experiences of left-behind (CELB), and maltreatments (CEMTs) including beating (CEB), neglect (CEN), sexual abuse (CESA), recent stress, and current depression (measured by the 9-item Patient Health Questionnaire). RESULTS: The correlation of Individual CAs and recent stress was significant. In addition to their significant independent/direct incremental effects, all surveyed CAs were associated with increased severity of early-adult depression, and increased frequency of clinically significant depression (CSD), through significant associations with recent stress (mediation effect). History of CEMTs including CEB, CEN, and CESA significantly increased the effects of recent stress on depression (moderation effect). CONCLUSIONS: Chinese undergraduate students reported frequent history of exposure to CAs, which increased the likelihood of depression in early adulthood, not only directly but also through the increasing the likelihood (mediation effect) and impact (moderation effect) of recent stress on depression. These novel findings may help to extend our understanding of environmental determinants of depression, and to guide further research, clinical practice, and policy in this context.

Functional Connectivity of Nucleus Accumbens and Medial Prefrontal Cortex With Other Brain Regions During Early-Abstinence Is Associated With Alcohol Dependence and Relapse: A Resting-Functional Magnetic Resonance Imaging Study.

Background: Alcohol dependence (AD) is a chronic recurrent brain disease that causes a heavy disease burden worldwide, partly due to high relapse rates after detoxification. Verified biomarkers are not available for AD and its relapse, although the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) may play important roles in the mechanism of addiction. This study investigated AD- and relapse-associated functional connectivity (FC) of the NAc and mPFC with other brain regions during early abstinence. Methods: Sixty-eight hospitalized early-abstinence AD male patients and 68 age- and education-matched healthy controls (HCs) underwent resting-functional magnetic resonance imaging (r-fMRI). Using the NAc and mPFC as seeds, we calculated changes in FC between the seeds and other brain regions. Over a follow-up period of 6 months, patients were measured with the Alcohol Use Disorder Identification Test (AUDIT) scale to identify relapse outcomes (AUDIT ≥ 8). Results: Thirty-five (52.24%) of the AD patients relapsed during the follow-up period. AD displayed lower FC of the left fusiform, bilateral temporal superior and right postcentral regions with the NAc and lower FC of the right temporal inferior, bilateral temporal superior, and left cingulate anterior regions with the mPFC compared to controls. Among these FC changes, lower FC between the NAc and left fusiform, lower FC between the mPFC and left cingulate anterior cortex, and smoking status were independently associated with AD. Subjects in relapse exhibited lower FC of the right cingulate anterior cortex with NAc and of the left calcarine sulcus with mPFC compared to non-relapsed subjects; both of these reductions in FC independently predicted relapse. Additionally, FC between the mPFC and right frontal superior gyrus, as well as years of education, independently predicted relapse severity. Conclusion: This study found that values of FC between selected seeds (i.e., the NAc and the mPFC) and some other reward- and/or impulse-control-related brain regions were associated with AD and relapse; these FC values could be potential biomarkers of AD or for prediction of relapse. These findings may help to guide further research on the neurobiology of AD and other addictive disorders.

Differential effects of different antipsychotic drugs on cognitive function in patients with chronic schizophrenia.

BACKGROUND: Cognitive impairment is core feature of schizophrenia. The impact of antipsychotics on cognition remains controversial. This study aimed to examine the effects of long-term use of different types of antipsychotics on cognitive impairment in schizophrenia patients. METHODS: We used the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to assess the cognition of three groups of schizophrenia patients (318 on clozapine, 125 on risperidone, and 166 on typical antipsychotic drugs) and 399 healthy controls, and used the Positive and Negative Syndrome Scale to assess schizophrenia symptoms of patients. RESULTS: Patients taking typical antipsychotics scored higher on the immediate memory and delayed memory index than those taking clozapine or risperidone (all p < 0.01). Patients taking clozapine scored higher on the language subscale than those taking risperidone (p < 0.05). Multiple regression analysis showed that the drug type was identified as an independent contributor to the immediate memory, language, and delayed memory index of RBANS (all p < 0.05). CONCLUSIONS: Patients taking typical antipsychotics have better memory than those taking clozapine or risperidone. Patients taking clozapine have better language function than those taking risperidone.

Elevated activity of plasma superoxide dismutase in never-treated first-episode schizophrenia patients: Associated with depressive symptoms.

Oxidative stress in excess may be engaged in the pathophysiological development of schizophrenia (SCZ). Previous research showed altered activity of superoxide dismutase (SOD) in patients suffering from SCZ, with inconsistent results. However, few studies have analyzed the relationship between SOD activity and psychopathological symptoms in never-treated first-episode (NTFE) patients with SCZ. The activities of manganese SOD (MnSOD) and total SOD were measured in a large sample of 166 NTFE patients with SCZ, and 133 healthy controls. The patients' symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS), as well as the depressive and cognitive factors originated from the PANSS five-factor model. NTFE patients had significantly higher activities of MnSOD and total SOD than healthy controls (both p < 0.01). Correlation analysis displayed a notably positive correlation between both MnSOD or total SOD activities and the PANSS depressive factor, as well as between MnSOD activity and the PANSS general psychopathology subscale score (all p < 0.05). Stepwise multiple regression analysis revealed that both MnSOD and total SOD were independent factors affecting PANSS depressive factor and PANSS general psychopathology subscale score. Our findings suggest that increased SOD activity may be associated with comorbid depressive symptoms in NTFE patients with SCZ.

The prevalence, risk factors and clinical correlates of diabetes mellitus in Chinese patients with schizophrenia.

Diabetes is one of the most common comorbid diseases in patients with schizophrenia. The present study examined the prevalence of diabetes and its clinical correlates in a large sample of Chinese patients with schizophrenia, which has not been examined systemically. In this cross-sectional study, a total of 1189 patients (males/females = 938/251; average age: 48.51 ± 10.09 years) were recruited. Fasting blood samples were collected to diagnose diabetes. Psychiatric symptoms were measured with the Positive and Negative Syndrome Scale (PANSS). The prevalence of diabetes was 12.53% with a significant gender difference (males: 10.87% versus females: 18.73%). Compared to patients without diabetes, those with diabetes were older, had a later age of onset, had a higher BMI, had higher positive symptom scores and had higher level of metabolic indices, including triglyceride, cholesterol and HDL cholesterol. After stepwise binary logistic regression analysis, age, BMI, and triglyceride level remained significantly associated with diabetes. This study suggests that diabetes occur with high prevalence in Chinese schizophrenia patients. In addition, age, BMI, and triglyceride level possibly are useful markers predicting an increased risk for diabetes.

P50 inhibition deficit in patients with chronic schizophrenia: Relationship with cognitive impairment of MATRICS consensus cognitive battery.

OBJECTIVE: Cognitive impairment is a core symptom of schizophrenia (SCZ); however, its pathophysiological mechanisms remain unclear. The sensory gating (SG) deficits reflected by P50 inhibition are recurring in SCZ, and this inhibition may be related to the cognitive deficits seen in these individuals. This study aimed to investigate the relationship between P50 inhibition and cognitive dysfunction in SCZ, which has not been fully investigated up to this point. METHODS: A total of 270 individuals with chronic SCZ and 116 healthy controls were enrolled in the study. Psychopathology of SCZ was rated by the positive and negative syndrome scale (PANSS), while cognitive function and P50 inhibition of subjects were assessed by the MATRICS Consensus Cognitive Battery (MCCB) and the electroencephalography system. RESULTS: The MCCB total and its 10 index scores were significantly lower in patients than those in healthy controls (all p < 0.001). SCZ patients had a lower amplitude of S1, and higher P50 ratio than healthy controls (both p < 0.01). However, there were no significant correlations between the P50 ratio and any of the PANSS total and its subscale scores in SCZ patients (all p > 0.05). Moreover, no correlation was found between the P50 components and the MCCB scores (all p > 0.05). CONCLUSIONS: Our findings suggest that the P50 inhibition deficits occur in Chinese individuals with SCZ, which may not be associated with their clinical symptoms and cognitive impairment.

Sex Differences in the Prevalence and Clinical Features of Comorbid Depressive Symptoms in Never-Treated Chinese Patients With First-Episode Schizophrenia.

BACKGROUND: Many studies have indicated a sex-specific effect in many aspects of schizophrenia. The presence of depressive symptomatology exists in all phases of schizophrenia. The aim of this study is to investigate the sex differences in the proportion of comorbid depressive symptoms and sex-specific relationships between depressive symptoms and clinical correlates in never-treated Chinese patients with first-episode schizophrenia (NTFE patients), which have not been reported yet. METHODS: Via a cross-sectional design, 240 NTFE inpatients (male/female = 111/129) between ages 16 and 45 years and meeting DSM-IV-TR criteria of schizophrenia were recruited. The Positive and Negative Syndrome Scale (PANSS) was used for the psychopathology, and the 17-item Hamilton Depression Rating Scale (HDRS-17) for the comorbid depressive symptoms. This study was conducted from June 2013 to December 2015. RESULTS: The proportion of patients with depressive symptoms (total score on HDRS-17 ≥ 8) in men was significantly higher than in women (male: 62.2%, female: 48.1%; χ²1 = 4.28, P = .039). Male patients had significantly greater depressive symptoms as shown on the HDRS-17 than female patients (t1, 238 = 2.75, P = .006). Further, we found that age, the age at onset, smoking rate, and PANSS total and general psychopathology, negative symptoms, and cognitive factor subscores favored significant sex differences in female patients (all P < .05). Interestingly, we found sex differences in the correlation between the HDRS-17 score and clinical phenotype, showing that in male patients, the PANSS general psychopathology subscore (ß = 0.75, t = 7.72, P < .001) and total score (ß = 0.44, t = 4.81, P < .001) significantly predicted the HDRS-17 total score, while in female patients, the PANSS general psychopathology subscore (ß = 0.74, t = 8.45, P < .001), total score (ß = 0.47, t = 5.71, P < .001), and cognitive factor subscore (ß = 0.24, t = 2.60, P < .001) significantly predicted the HDRS-17 total score. CONCLUSIONS: Our results indicate sex differences in the frequency and severity of comorbid depressive symptoms and in associations between depressive symptoms and clinical correlates in NTFE patients.

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.