Search

Rationale: 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., Objectives: 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., Methods: 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)., Results: 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)., Conclusions: 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., Competing Interests: Declarations Declarations of interest No conflict of interest was disclosed for each author., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rationale and Objective: Schizophrenia displays sex differences in many aspects. Decreased brain-derived neurotrophic factor (BDNF) levels have been reported to be associated with high body weight or obesity as well as other psychopathological aspects in schizophrenia patients. This study aimed to explore sex differences in the relationship between serum BDNF levels and obesity in patients with chronic schizophrenia., Methods: We recruited 132 Chinese patients with chronic schizophrenia (98 males and 34 females) and compared sex differences in the body mass index (BMI), obesity, serum BDNF levels, and their associations. Psychopathology symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). A regression model with various demographic and clinical variables was applied to predict the serum levels of BDNF., Results: Female patients had a higher rate of obesity and higher BMI, but lower BDNF levels than male schizophrenia patients. A significantly negative correlation was observed between BMI and BDNF levels only in female patients but not in male patients. The multiple regression model with demographic and clinical variables significantly predicted BDNF levels only in female patients, with a medium size effect. And only in female patients, BMI made a significant contribution to this prediction., Conclusion: Our results indicate significant sex differences in the obesity, BMI, BDNF levels, and their association in chronic patients with schizophrenia, showing a significant inverse correlation between BMI and BDNF levels only in female patients. Thus, sex needs to be considered when assessing the relationship between BDNF and metabolic syndromes in schizophrenia.

Objective: Many studies have reported that long-term exposure to job-related stress can lead to burnout, which may be influenced by genetic and environmental factors. Burnout correlates with depression. This study investigated whether one tag polymorphism rs6354 in 5-HTT gene modulated the influence of job-related stress on burnout in the medical professionals in a Chinese Han population, which to our best knowledge has not been explored., Methods: Seven hundred twelve subjects were recruited from a general hospital and measured for burnout symptoms using the Maslach Burnout Inventory (MBI), the stress using the House and Rizzo's Work Stress Scale, and the stressors using the Evers, Frese, and Cooper's Sources of Pressure Scale. The 5-HTT rs6354 polymorphism was genotyped in 376 subjects., Results: The majority of correlations between the work stress score or the six stressor scores and three burnout subscores were significant (all p < 0.05). There was no significant main effect of the 5-HTT rs6354 genotype on burnout symptoms; however, there was a statistically significant interaction between 5-HTT rs6354 and work stress on burnout (F = 5.08, df = 2, 369, p = 0.007). In the low stress group, G allele carriers had significantly higher burnout level than TT homozygote (F = 11.60, df = 1, 48, p < 0.001). On the contrary, in the high stress group, G allele carriers exhibited significantly lower burnout level compared to TT homozygote (F = 3.86, df = 1, 103, p = 0.025)., Conclusions: Our findings suggest that the 5-HTT rs6354 polymorphism may modulate the influence of job-related stress on burnout by adjusting serotonin transporter function and neurotransmission, showing that individuals with TT genotype displayed a greater susceptibility to both the detrimental effects of higher stress and the beneficial effects of lower stress compared to those with G allele, which supports the differential-susceptibility hypothesis.

Objective: Few studies have examined the potential interactive effect of both smoking and drinking on cognition. Brain-derived neurotrophic factor (BDNF) plays a critical role in cognition. This is the first study to examine the neurocognitive consequences of cigarette smoking combined with chronic alcohol consumption and their relationship to serum BDNF levels in a Chinese Han population., Materials and Methods: We recruited 191 healthy male subjects, including 47 isolated smokers, 31 isolated chronic alcohol users, 58 combined smokers and chronic alcohol users, and 55 non-smokers and non-alcohol users. We then compared the repeatable battery for the assessment of neuropsychological status (RBANS) scores and serum BDNF levels in these four groups., Results: When compared to the non-smoking + non-alcohol-using group, the smoking group performed worse on immediate memory, attention, language, and RBANS total score. There were no significant differences in the RBANS scores between the alcohol-using group and non-smoking + non-alcohol-using group, or between the smoking group and smoking + alcohol-using group. We did not find an association between BDNF and smoking or drinking status or between BDNF and cognitive performance. In the smoking group, there was a significant correlation between BDNF and carbon monoxide concentration, and between BDNF and the Fagerstrom Test for Nicotine Dependence (FTND) total score., Conclusions: Our results suggest that smoking is associated with cognitive decline, but not with BDNF levels in a normal population. However, smoking severity is positively associated with BDNF levels. Concomitant alcohol use does not worsen the cognitive decline caused by smoking.

Objective: A substantial body of evidence implicates TNF-alpha (TNFα) and TNFα-related signaling pathways in the pathophysiology of schizophrenia. The current study examined the relationship between TNFα serum levels and both psychopathological as well as cognitive symptoms in schizophrenia., Materials and Methods: Serum TNFα levels were assessed in 89 patients diagnosed with schizophrenia and compared to 43 healthy control subjects matched for age and gender. Schizophrenic symptomatology was assessed with the Positive and Negative Syndrome Scale (PANSS), and serum TNFα levels were measured by sandwich enzyme-linked immunosorbent assay (ELISA)., Results: TNFα levels were significantly lower in patients with chronic schizophrenia relative to healthy control subjects (p<0.01). Correlation analysis revealed a significant negative correlation between the TNFα levels and the PANSS total score (p<0.01). Additionally, TNFα levels were significantly negatively correlated with scores on general psychopathology (p<0.01), positive (p<0.05) and cognitive subscales (p<0.05). Stepwise multiple regression analysis identified TNFα levels as a significant predictor of scores on the general psychopathology subscale of the PANSS., Conclusion: The significant relations observed in the current study between TNFα and the PANSS and its subscales suggest that immune disturbance may be involved in the psychopathology and cognitive deficits of schizophrenia.

Background: Long-term antipsychotic treatment for schizophrenia is often associated with the emergence of tardive dyskinesia (TD), which is linked to greater cognitive impairment. Brain-derived neurotrophic factor (BDNF) plays a critical role in cognitive function, and schizophrenia patients with TD have lower BDNF levels than those without TD., Objective: This study examines the BDNF levels, the cognitive function, and the association of BDNF with cognitive function in schizophrenia patients with or without TD., Methods: We recruited 83 male chronic patients with (n=35) and without TD (n=48) meeting DSM-IV criteria for schizophrenia and 52 male control subjects. We examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and BDNF levels for all subjects. Positive and Negative Symptom Scale (PANSS) and the Abnormal Involuntary Movement Scale (AIMS) were assessed in patients., Results: BDNF levels were lower in patients with than those without TD (p<0.05). RBANS total score (p<0.01) and subscales of immediate memory, visuospatial/constructional performance, and attention were lower in patients with than those without TD (all p<0.05). BDNF levels were positively associated with immediate memory in patients without TD, but negatively in TD patients (both p<0.05). Multiple regression analysis confirmed that in either TD or non-TD group, BDNF was an independent contributor to immediate memory (both p<0.05)., Conclusions: BDNF may be involved in the pathophysiology of TD. While the associations between BDNF and cognition in both TD and non-TD patients suggest a close relationship between BDNF and cognition, the different directions may implicate distinct mechanisms between TD and non-TD patients.

The available literature on the use of atypical antipsychotics for the treatment of bipolar disorder was reviewed. All uncontrolled and controlled reports were identified through a comprehensive Medline search. Based on the available evidence, olanzapine was found to be the most appropriate atypical antipsychotic agent utilized for the treatment of manic bipolar patients, although there is also preliminary data suggesting the efficacy of risperidone and clozapine. The preliminary data evaluating the efficacy of quetiapine and ziprasidone in bipolar disorder are still very limited. Double-blind controlled studies with atypical antipsychotics in the long-term treatment of bipolar disorder are still largely not available, but will be critical to determine the effectiveness of these agents in the maintenance treatment of bipolar disorder. There are recent uncontrolled suggestions that olanzapine may have beneficial effects in depressed bipolar patients, which deserve further investigation in controlled studies. In conclusion, atypical antipsychotics, due to lower potential for neurotoxicity and preliminary evidence suggesting better efficacy than typical antipsychotics, are increasingly having a more prominent role in the pharmacological management of bipolar patients. Nonetheless, until there is systematic data from long-term controlled follow-up studies on the comparative efficacy of these agents with mood stabilizers, atypical antipsychotics should be cautiously utilized, and preferably in combination with a mood stabilizer for the maintenance phase of treatment.

Rationale: In vitro and in vivo animal studies suggest that the intracellular phosphatidylinositol (PI) pathway is an important target for the effects of lithium., Objectives: We conducted a preliminary study to examine the in vivo effects of lithium treatment on platelet membrane phosphoinositides in bipolar disorder subjects, in an attempt to examine further the hypothesis that lithium has significant in vivo effects on the PI pathway in these patients., Methods: We quantitated PI, phosphatidylinositol-4-phosphate (PIP), and phosphatidylinositol-4,5-bisphosphate (PIP2) in platelet membranes of seven subjects (five male, two female; mean age= 27.9+/-5.7 years), initially while they were unmedicated, and a second time after at least 21 days of lithium treatment (mean+/-SD=28.7+/-7.1 days)., Results: The mean+/-SD values for PI were 5.63+/-2.25% and 5.21+/-1.06%; for PIP 0.68+/-0.20% and 0.55+/-0.11%; and for PIP2 0.60+/-0.21% and 0.38+/-0.15%, before and after lithium treatment, respectively. The decrease in PIP2 values after lithium treatment was statistically significant (Wilcoxon signed ranks test, Z=-2.37, P=0.02)., Conclusion: This longitudinal study suggests that therapeutic doses of lithium significantly decrease platelet membrane PIP2 levels in vivo in bipolar disorder subjects, which may be related to lithium's mechanism of action in bipolar disorder.

Limited data exists on mechanisms contributing to elevated risk for alcohol use disorder (AUD) in bipolar disorder. Variation in subjective response to alcohol may relate to alcohol use and risk for AUD. This study used a randomized, placebo-controlled, cross-over, within-subjects design to investigate differences in subjective response to alcohol in 50 euthymic young adults (n = 24 with and n = 26 without bipolar disorder type I). Eighty-three percent of participants with bipolar disorder were medicated. Participants completed assessments of clinical history, alcohol expectancies, and recent alcohol use. Participants were dosed to a .08 g% breath alcohol concentration. The placebo condition occurred on a separate counter-balanced day. Subjective response to alcohol was investigated at similar time points during both conditions. Group, condition, and group-by-condition interactions were modeled, with condition and time of subjective response assessment as repeated within-subject variables, and subjective response to alcohol as the dependent variable. Greater stimulating effects and liking of alcohol were reported in people with bipolar disorder (group-by-condition interactions, p < .05) than healthy young adults. While young adults with bipolar disorder reported anticipating feeling less "mellow/relaxed" when drinking (p = .02), during both beverage conditions they reported feeling more "mellow/relaxed" (main effect of group, p = .006). Feeling more "mellow/relaxed" during the alcohol condition related to greater recent alcohol use in bipolar disorder (p = .001). Exploratory analyses suggested anticonvulsants and sedatives/antihistamines may relate to differences in subjective response to alcohol in bipolar disorder. Results suggest young adults with bipolar disorder may differ in alcohol expectancies and experience alcohol intoxication differently-with distinct relations between subjective response to alcohol and alcohol use-compared to healthy young adults., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Deep brain stimulation (DBS) delivered to the ventromedial prefrontal cortex (vmPFC) induces antidepressant- and anxiolytic-like responses in various animal models. Electrophysiology and neurochemical studies suggest that these effects may be dependent, at least in part, on the serotonergic system. In rodents, vmPFC DBS reduces raphe cell firing and increases serotonin (5-HT) release and the expression of serotonergic receptors in different brain regions., Methods: We examined whether the behavioural responses of chronic vmPFC DBS are mediated by 5-HT 1A or 5-HT 1B receptors through a series of experiments. First, we delivered stimulation to mice undergoing chronic social defeat stress (CSDS), followed by a battery of behavioural tests. Second, we measured the expression of 5-HT 1A and 5-HT 1B receptors in different brain regions with western blot. Finally, we conducted pharmacological experiments to mitigate the behavioural effects of DBS using the 5-HT 1A antagonist, WAY-100635, or the 5-HT 1B antagonist, GR-127935., Results: We found that chronic DBS delivered to stressed animals reduced the latency to feed in the novelty suppressed feeding test (NSF) and immobility in the forced swim test (FST). Though no significant changes were observed in receptor expression, 5-HT 1B levels in DBS-treated animals were found to be non-significantly increased in the vmPFC, hippocampus, and nucleus accumbens and reduced in the raphe compared to non-stimulated controls. Finally, while animals given vmPFC stimulation along with WAY-100635 still presented significant responses in the NSF and FST, these were mitigated following GR-127935 administration., Conclusions: The antidepressant- and anxiolytic-like effects of DBS in rodents may be partially mediated by 5-HT1 B receptors., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rationale: Patients with schizophrenia with second-generation antipsychotics (SGAs) treatment have shown an increased risk of bone fragility and susceptibility to fracture; however, it is still unclear whether this risk is derived from the effect of antipsychotics on balance of bone metabolism., Objectives: We investigated the changes of two bone turnover biomarkers (BTMs) concentrations in people with schizophrenia receiving SGAs: procollagen type I aminoterminal propeptide (PINP) and C-terminal telopeptide of type I collagen (CTX-1) as BTMs of osteogenesis and bone resorption, respectively, to explore how antipsychotics contribute to bone fragility., Methods: We recruited 59 Chinese male patients with schizophrenia (32 drug-naïve first-episode (DNFE) patients and 27 chronic patients) to undergo 8 weeks SGAs treatment. Fasting peripheral blood samples of pre- and posttreatment were collected, plasma levels of PINP and CTX-1 were measured., Results: The interaction effects of group and time on PINP and CTX-1 concentrations were found (P = .016 and P = .008). There was a significant decrease for both BTMs concentrations of the posttreatment compared to the pretreatment (P<.001 and P = .003). Chronic patients had significantly higher changes of BTMs concentrations compared to DNFE patients (P = .048 and P = .024). There was a positive correlation of the two BTMs of pretreatment with disease course in DNFE group (r = .37, P = .039;r = .38, P = .035) and a negative correlation of PINP of pretreatment with age in the chronic group (r=-.40, P = .039)., Conclusion: Long-term SGAs medication inhibited osteogenesis in a dose- and time-dependent manner and damaged the balance of bone formation and bone resorption., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rationale: Job stress can lead to job burnout, and BDNF polymorphism has been found to be involved in its psychopathological mechanism. Research needs a better understanding of the important role of gene × environment (i.e., BDNF polymorphism × job stress) interaction on job burnout., Objective: This study aimed to explore how BDNF rs6265 polymorphism may moderate the relationship between job stress and job burnout., Methods: Three hundred forty-one healthy participants (187 males and 154 females) from a Chinese university were included. The present study used a standardized questionnaire including demographic characteristics, job stress assessed by the House and Rizzo's Work Stress Scale, and job burnout assessed by the Maslach Burnout Inventory-General Survey. The BDNF rs6265 polymorphism was genotyped., Results: Job stress showed a positive correlation with emotional exhaustion (p < 0.001), cynicism (p < 0.001), and reduced personal accomplishment (p < 0.01). The main effects of BDNF rs6265 polymorphism on emotional exhaustion and cynicism were significant [F (1,333)  = 5.136, p = 0.024; F (1,333)  = 4.175, p = 0.042, respectively]. The interaction between job stress and BDNF rs6265 on cynicism was significant (△ R 2  = 0.013, p = 0.014) after controlling for age, sex, education, and position, indicating that individuals with BDNF rs6265 TT genotype showed higher level of cynicism when in high job stress., Conclusions: The results provided evidence for the association of BDNF gene rs6265 polymorphism, job stress, and their interaction with job burnout. Individuals with TT genotype in BDNF rs6265 might be susceptible to stressful situations, which would lead to cynicism., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: People with schizophrenia exhibit a high obesity rate. However, little is known about the prevalence of obesity and its relationship with clinical symptoms and metabolic indicators in first-episode drug-naïve (FEDN) schizophrenia., Methods: Demographic and lipid parameters were gathered from 297 FEDN schizophrenia and 325 healthy controls. The patients' symptomatology was evaluated by the Positive and Negative Syndrome Scale (PANSS)., Results: The obesity rate of FEDN patients was 10.77%, similar to that of controls (10.5%). The prevalence of overweight plus obesity of patients was 44.8%, significantly higher than that of controls (36.6%). Compared with non-obese patients, obese patients had higher levels of cholesterol (4.81 ± 0.93 vs 4.22 ± 1.00 mmol/L), triglyceride (0.27 ± 0.21 vs 0.14 ± 0.24 mg/dL), low-density lipoprotein (0.48 ± 0.12 vs 0.40 ± 0.12 mg/dL), greater ratio of triglyceride/high-density lipoprotein (2.01 ± 1.23 vs 1.44 ± 1.26), and higher PANSS positive symptom subscale score (29.81 ± 6.29 vs 27.05 ± 6.15), general psychopathology subscale score (70.75 ± 11.74 vs 66.87 ± 11.37), and total score (149.81 ± 21.08 vs 140.64 ± 21.58), but lower high-density lipoprotein level (1.09 ± 0.21 vs 1.27 ± 0.34 mg/dL) (all p < 0.05). Correlation analysis revealed that body mass index (BMI) was positively correlated with triglyceride, cholesterol, high-density lipoprotein, low-density lipoprotein, triglyceride/high-density lipoprotein ratio, PANSS positive symptoms, general psychopathology, and total scores (all p < 0.05, r = 0.124 ~ 0.335). Multiple regression analysis confirmed that PANSS positive symptoms, total score, and cholesterol level were significantly associated with BMI (all p < 0.05, β: 0.126-0.162)., Conclusion: There was no significant difference in the prevalence of obesity between FEDN patients and the control group. Moreover, BMI was positively associated with positive symptom severity in FEDN patients.

Background: Rapid-eye movement (REM) sleep deprivation (SD) can induce manic-like behaviors in rodents. On the other hand, lithium, as one of the oldest drugs used in neuropsychiatric disorders, is still one of the best drugs for the treatment and control of bipolar disorder. In this study, we aimed to investigate the role of chronic short-term REM SD in the induction of manic-like behaviors in female rats., Methods: The rats were exposed to REM SD for 14 days (6 hours/day). Lithium was intraperitoneally injected at the doses of 10, 50, and 100 mg/kg., Results: REM SD induced hyperactivity and OCD-like behavior, and decreased anxiety, depressive-like behavior, and pain subthreshold. REM SD also impaired passive avoidance memory and decreased hippocampal brain-derived neurotrophic factor (BDNF) expression level. Lithium at the doses of 50 and 100 mg/kg partly and completely abolished these effects, respectively. However, lithium (100 mg/kg) increased BDNF expression level in control and sham REM SD rats with no significant changes in behavior., Conclusions: Chronic short-term REM SD may induce a mania-like model and lead to OCD-like behavior and irritability. In the present study, we demonstrated a putative rodent model of mania induced by chronic REM SD in female rats. We suggest that future studies should examine behavioral and mood changes following chronic REM SD in both sexes. Furthermore, the relationship between manic-like behaviors and chronic REM SD should be investigated., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rationale: Challenges in drug development for psychiatric disorders have left much room for the introduction of novel treatments with better therapeutic efficacies and indices. As a result, intense research has focused on identifying new targets for developing such pharmacotherapies. One of these targets may be the phosphodiesterase (PDE) class of enzymes, which play important roles in intracellular signaling. Due to their critical roles in cellular pathways, these enzymes affect diverse neurobiological functions from learning and memory formation to neuroinflammation., Objectives: In this paper, we reviewed studies on the use of PDE inhibitors (PDEIs) in preclinical models and clinical trials of psychiatric disorders including depression, anxiety, schizophrenia, post-traumatic stress disorder (PTSD), bipolar disorder (BP), sexual dysfunction, and feeding disorders., Results: PDEIs are able to improve symptoms of psychiatric disorders in preclinical models through activating the cAMP-PKA-CREB and cGMP-PKG pathways, attenuating neuroinflammation and oxidative stress, and stimulating neural plasticity. The most promising therapeutic candidates to emerge from these preclinical studies are PDE2 and PDE4 inhibitors for depression and anxiety and PDE1 and PDE10 inhibitors for schizophrenia. Furthermore, PDE3 and 4 inhibitors have shown promising results in clinical trials in patients with depression and schizophrenia., Conclusions: Larger and better designed clinical studies of PDEIs in schizophrenia, depression, and anxiety are warranted to facilitate their translation into the clinic. Regarding the other conditions discussed in this review (most notably PTSD and BP), better characterization of the effects of PDEIs in preclinical models is required before clinical studies., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rationale: Opioid use disorder is a complicated brain disease with high heritability. The underlying mechanisms of the genetic underpinnings in the susceptibility and treatment response of opioid use disorder remain elusive., Objectives: To reveal the potential associations of genotypes and gene methylations of dopaminergic system genes, as well as roles of them in opioid use disorder. In the present study, we detected the DNA methylation in the promoter regions of five representative dopaminergic system genes (DRD1, DRD2, SLC6A3, TH, and COMT) between 120 patients with heroin use disorder in methadone maintenance treatment (MMT) program and 111 healthy controls. The associations of 25 SNPs in the above genes and methylation of 237 CpG sites, known as methylation quantitative trait loci (mQTLs), were determined. Then, the correlations of the above mQTLs and traits of heroin use disorder were analyzed in a sample set of 801 patients with heroin use disorder and 930 healthy controls., Results: Our results demonstrated that several mQTLs in the DRD1 and DRD2 genes were identified both in the heroin use disorder and healthy control groups. Interestingly, rs4867798-CpG&#95;174872884 and rs5326-CpG&#95;174872884 in the DRD1 gene were the unique SNP-CpG pairs in the patients with heroin use disorder. Furthermore, mQTL rs5326 was associated with the susceptibility and effective dosage of MMT for heroin use disorder, and demonstrated allele-specific correlation with the expression of the DRD1 gene in the human caudate., Conclusions: Our findings suggest that some mQTLs may be associated with traits of opioid use disorder by implicating the DNA methylation and gene expression., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rationale: Although metabolic abnormalities and metabolic syndrome (MetS) have been extensively investigated in schizophrenia, few studies have examined them in first-episode drug-naive (FEDN) patients., Objectives: This study aimed to investigate the prevalence and clinical correlates of metabolic abnormalities in FEDN schizophrenia patients., Methods: A total of 430 FEDN schizophrenia patients and 453 controls were recruited. Various parameters were measured including BMI, waist circumference, blood pressure, lipid profiles, blood glucose, glycosylated hemoglobin (HbA1c), insulin, and homeostatic model assessment for insulin resistance (HOMA-IR)., Results: Patients had a higher prevalence of MetS, hypertension, hypertriglyceridemia, hypo-HDL-C, elevated HAb1c, and elevated insulin than controls (19.1% vs. 6.6%, OR = 2.52; 33.3% vs. 12.1%, OR = 3.05; 30.5% vs. 16.1%, OR = 2.25; 43.1% vs. 24.0%, OR = 2.21; 25.6% vs. 10.8%, OR = 2.62; 9.1% vs. 0.9%, OR = 10.29; all p Bonferroni  < 0.001). Waist circumference was associated with PANSS general psychopathology and total score (correlation coefficient r = 0.17, p Bonferroni  < 0.001; correlation coefficient r = 0.16, p Bonferroni  = 0.004). Fasting glucose was associated with PANSS negative, general psychopathology, and total score (correlation coefficient r = 0.13, p Bonferroni  = 0.03; correlation coefficient r = 0.19, p Bonferroni  < 0.001; correlation coefficient r = 0.20, p Bonferroni  < 0.001). BMI (OR = 1.37), smoking (OR = 3.39), and HOMA-IR (OR = 5.60) were associated with MetS in FEDN schizophrenia (all p < 0.001)., Conclusions: Our results demonstrate that MetS and metabolic abnormalities co-existed in the early stages of schizophrenia without antipsychotics. Waist circumference and glucose were associated with psychopathological symptoms, while BMI, smoking, and HOMA-IR were associated with MetS in FEDN schizophrenia., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rationale: Autism spectrum disorders (ASDs) are highly prevalent neurodevelopmental disorders characterized by deficits in social communication and interaction, repetitive stereotyped behaviors, and cognitive impairments. Curcumin has been indicated to be neuroprotective against neurological and psychological disorders. However, the role of curcumin in autistic phenotypes remains unclear., Objectives: In the current study, we evaluated the effects of neonatal curcumin treatment on behavior and hippocampal neurogenesis in BTBRT + ltpr3 tf /J (BTBR) mice, a model of autism., Methods: C57BL/6J (C57) and BTBR mouse pups were treated with 0.1% dimethyl sulfoxide (DMSO) or curcumin (20 mg/kg) from postnatal day 6 (P6) to P8. Neural progenitor cells (NPCs) in the hippocampal dentate gyrus (DG) were evaluated on P8, and neurogenesis was measured on P24 by immunofluorescence. A battery of behavioral tests was carried out when the mice were 8 weeks of age., Results: Neonatal curcumin treatment improved autism-related symptoms in BTBR mice, enhancing sociability, reducing repetitive behaviors, and ameliorating cognitive impairments. Furthermore, the suppression of hippocampal neurogenesis in BTBR mice was greatly rescued after neonatal curcumin treatment, leading to an increase in neurogenic processes and an increase in NPC proliferation concomitant with an expansion of the NPC pool on P8, and NPC differentiation towards the neuronal lineage was promoted in the DG of BTBR mice on P24., Conclusions: Our findings suggest that neonatal curcumin treatment elicits a therapeutic response through the restoration of hippocampal neurogenesis in BTBR mice and thus may represent a promising novel pharmacological strategy for ASD treatment.

Rationale: The volatile anesthetic isoflurane is suggested to produce a rapid and robust antidepressive effect in preliminary clinical trials. Recently, isoflurane was found to activate the tropomyosin receptor kinase B (TrkB) signaling which is the underlying mechanism of the rapid antidepressant ketamine., Objective: Our study investigated the effect of isoflurane anesthesia on chronic unpredictable mild stressed (CUMS) model in mice and verified the role of brain-derived neurotrophic factor (BDNF)/TrkB/ the mammalian target of rapamycin (mTOR) signaling in the antidepressant effect of isoflurane., Methods: We employed the CUMS model of depression to assess the rapid antidepressant effect of isoflurane by the forced swimming test (FST), the sucrose preference test (SPT), and the novelty suppressed feeding test (NSFT). The protein expression of BDNF and TrkB/protein kinase B (PKB or Akt)/mTOR was determined through Western blot. The dendritic spine density in the hippocampus and medial prefrontal cortex (PFC) was measured by the Golgi staining., Results: A brief burst-suppressing isoflurane anesthesia rapidly reversed the behavioral deficits caused by CUMS procedure, normalized the expression of BDNF and further activated the TrkB signaling pathway in CUMS-induced stressed mice in both prefrontal cortex (PFC) and hippocampus (HC). All of those behavioral and proteomic effects were blocked by K252a, a selective receptor inhibitor of TrkB. Isoflurane significantly promoted the formation of dendritic spines in both medial prefrontal cortex (mPFC), CA1, CA3, and DG of the hippocampus., Conclusion: Our study indicates that isoflurane exerts a rapid antidepressant-like effect in CUMS depression animal model, and the activation of BDNF/TrkB signaling pathway plays an indispensable role in the biological and behavioral antidepressant effects of isoflurane. A single exposure to isoflurane could repair synaptic damage caused by chronic stimulation.

There is increasing evidence that connections formed between microbiome, the gut, and the brain play a role in health and well-being. Non-pharmaceutical targets for management of mood disorders, such as bipolar disorder, are relatively under-researched. At the same time, it is clear that there is an intimate connection between psychiatry and gastrointestinal health. Here, we have discussed various comorbid conditions associated with bipolar disorders such as inflammation, irritable bowel disease and antibiotic induced mania with importance to demonstrate possible involvement of the gut microbiota. Gut microbiota-targeted preclinical and clinical interventions have demonstrated enhancement in various psychological conditions. Further in this review, we explore links between bipolar disorder, inflammation and gut microbiome with a focus on dietary, pro- and pre-biotic interventions as potential adjuvant therapies for use in the management of mood disorders such as bipolar disorder.