Glucose Metabolism and Sex Hormones in Male Patients with Medication-naïve First-episode Schizophrenia: A Large-scale Cross-sectional Study.

BACKGROUND: Schizophrenia (SCZ) usually begins in early adult life. The underlying molecular mechanisms of SCZ remain unclear. There is evidence for the involvement of abnormalities in metabolic and endocrine systems in SCZ, even in drug-naïve first-episode schizophrenia patients (DNFES). However, the association between impaired regulation of glucose metabolism and sex hormones was not studied in SCZ. This study aimed to evaluate the interrelationship between sex hormones and high fasting glucose levels in male DNFES patients. METHODS: A total of 99 patients with SCZ were recruited, and fasting glucose, fasting insulin, the insulin resistance index (HOMA-IR), and sex hormones were measured. RESULTS: We found that some male patients with SCZ had abnormal levels in glucose metabolism parameters and gonadal hormones that were not within the normal range. Linear regression analysis adjusted for age, waist circumference, and body mass index showed that testosterone levels were negatively associated with fasting insulin in male patients (ß = -0.21, t = -2.2, p = 0.03). CONCLUSION: Our findings confirm the abnormalities in glucose metabolism parameters and gonadal hormones at the onset of the illness in male DNFES patients with SCZ. In addition, there was an interaction effect between abnormal glucose metabolism and sex hormones in male patients.

Interaction between baseline BMI and baseline disease severity predicts greater improvement in negative symptoms in first-episode schizophrenia.

Several studies have reported that baseline symptom severity in patients with schizophrenia (SCZ) is associated with the efficacy of antipsychotic medication. Overweight/obesity is common in SCZ and has also been reported to be correlated with therapeutic response to antipsychotics. This study aimed to evaluate whether baseline body mass index (BMI) and disease severity were associated with improvements in negative symptoms in patients with first-episode and medication-naïve (FEMN) SCZ. A total of 241 FEMN patients were recruited in this study and treated with oral risperidone over 3 months. Clinical symptoms were measured by the Positive and Negative Syndrome Scale (PANSS) and BMI was assessed at baseline and 3-month follow-up. We found that baseline BMI was correlated with the baseline severity of symptoms. Baseline BMI or baseline disease severity was associated with improvement in negative symptoms after 3 months of treatment. Linear regression analysis indicated that the interaction of BMI and disease severity at baseline was associated with improvement in negative symptoms in the early stage of SCZ after controlling for sex, age, and dose of risperidone. Our study suggests that the interaction of baseline BMI and disease severity may play a role in predicting negative symptom improvement after 3 months of risperidone treatment.

Correlations of religious beliefs with anxiety and depression of Chinese adolescents.

Objective: This study was designed to investigate the prevalence of religious belief and its relationship with psychiatric symptoms among Chinese adolescents. Methods: This study recruited 11,603 adolescents in Grades 7-9 from March 21 to 31, 2020 in five cities in China. The religious beliefs of adolescents were collected by asking whether they held religious beliefs and what type of religious beliefs they held. The Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 Scale (GAD-7) were used to assess depressive and anxiety symptoms in all adolescents. Demographics, religious beliefs, and mental health status were collected through the professional version of Wenjuanxing. Results: Of 11,069 valid questionnaires collected, 847 (7.7%) reported holding religious beliefs. Adolescents with religious beliefs showed significantly more severe symptoms of depression and anxiety compared to those without religious beliefs (both p<0.05). Logistic regression analysis revealed that religious belief was a risk factor for symptoms of depression (OR = 1.37, 95%CI: 1.16-1.61, p < 0.001) and anxiety (OR = 1.49, 95%CI: 1.23-1.79, p < 0.001) after controlling age, gender, and parental marital status. Conclusions: Our findings suggest that religiousness in adolescents was associated with a higher likelihood of depression/more intense depressive symptoms. In addition, religious Chinese adolescents should be provided with more resources to help them cope with mental health concerns.

Dance/movement therapy for improving metabolic parameters in long-term veterans with schizophrenia.

Accumulating evidence has supported the implementation of dance/movement therapy (DMT) as a promising intervention for patients with schizophrenia (SCZ). However, its effect on body weight and metabolic profile in SCZ remains unclear. This study aimed to evaluate the outcome of a 12-week DMT session on weight and lipid profile in patients with SCZ using a randomized, single-blinded, controlled trial design. This study encompassed two groups of long-term hospitalized patients with SCZ, who were randomly assigned to the DMT intervention (n = 30) or the treatment as usual (TAU) group (n = 30). Metabolic markers, including weight, body mass index (BMI), fasting glucose, triglycerides, and total cholesterol were measured in both groups at two measurement points (at baseline and the end of the 12-week treatment). We found that DMT intervention significantly decreased body weight (F = 5.5, p = 0.02) and BMI (F = 5.7, p = 0.02) as compared to the TAU group. However, no significance was observed in other metabolic markers, including fasting glucose, triglycerides, and total cholesterol after treatment (all p > 0.05). Our study indicates that a 12-week, 24-session DMT program may be effective in decreasing body weight and BMI in long-term hospitalized patients with SCZ. DMT intervention may be a promising treatment strategy for long-term inpatients in the psychiatric department.

The neutrophil-lymphocyte ratio in first-episode medication-naïve patients with schizophrenia: A 12-week longitudinal follow-up study.

Inflammation has been related to schizophrenia (SZ). The neutrophil-to-lymphocyte ratio (NLR) is an inexpensive inflammatory marker, however, its potential predictive value in patients with SZ has not been extensively investigated. This study aimed to examine whether NLR could predict the clinical response to antipsychotics in this population. One hundred and ninety-five medication-naïve first-episode schizophrenia (MNFES) patients were recruited and received treatment with risperidone for 12 weeks in the present study. Clinical symptoms were evaluated at week 0 and the end of 12 weeks of treatment using the PANSS scales. Complete blood counts were determined at baseline. We found that baseline NEU counts and NLR were positively associated with improvements in clinical symptoms in patients. In addition, MNFES patients with higher baseline NLR values showed a better treatment response to antipsychotics. Linear regression analysis revealed a predictive role of baseline NLR for the improvements of clinical symptoms in SZ patients. Our findings demonstrate that higher NLR was related to better improvements in symptoms after 12 weeks of treatment with antipsychotics, which renders it a promising biomarker of the response to antipsychotics in clinical practice.

A double-blind, randomized controlled study of the effects of celecoxib on clinical symptoms and cognitive impairment in patients with drug-naïve first episode schizophrenia: pharmacogenetic impact of cyclooxygenase-2 functional polymorphisms.

Chronic low-grade peripheral and central nervous system inflammation may have a role in the pathogenesis of schizophrenia (SCZ). Inhibition of cyclooxygenase-2 (COX2), the arachidonic acid pathway, may inhibit cytokine responses and minimize inflammation. In this study, we added the COX2 inhibitor celecoxib to risperidone monotherapy to examine its efficacy on clinical symptoms and cognitive deficits in drug-naïve first episode (DNFE) SCZ patients. First, we genotyped two polymorphisms (rs5275 and rs689466) in the COX-2 gene in a case-control study of 353 SCZ patients and 422 healthy controls. Ninety patients participated in a 12-week, double-blind, randomized, placebo-controlled trial of celecoxib 400 mg/day. We used the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to assess clinical symptoms and cognition. Our results show that the COX2 rs5275 polymorphism was significantly correlated with SCZ and positive symptoms. After 12-week treatment, celecoxib significantly improved the PANSS total and three subscale scores of SCZ patients. Furthermore, patients with the rs5275 TT genotype had greater improvement in PANSS total score than patients carrying the C allele. However, no significant difference in RBANS total and subscale scores existed between the celecoxib and placebo groups at week 12. Our findings suggest that COX2 inhibitors may be promising therapeutics for clinical symptoms rather than cognitive impairment in first episode SCZ patients. COX2 rs5275 gene polymorphism may be implicated in the development and the efficacy of treating clinical symptoms in SCZ.Trial Registration Number: The trial was registered with www.clinicaltrials.gov (NCT00686140).

Total antioxidant capacity, obesity and clinical correlates in first-episode and drug-naïve patients with schizophrenia.

BACKGROUND: Overweight/obesity is a growing concern in schizophrenia (SZ). A few studies have shown that excessive oxidative stress and abnormal antioxidants were associated with pathogenesis and psychiatric symptoms in first episode antipsychotics naïve (FEAN) patients with SZ. However, there is no study has explored the interrelationships between total antioxidant status (TAS) and the severity of psychiatric symptoms in the early stage of SZ. This study aimed to evaluate the impact of overweight/obesity on psychiatric symptoms in FEAN patients with SZ. METHODS: A total of 241 patients with FEAN SZ and 119 healthy controls were recruited and symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS). TAS levels were also measured in patients and healthy controls. RESULTS: We found a significant negative association between body mass index (BMI) and TAS in FEAN patients, but not in controls. In addition, BMI and TAS were negatively associated with psychiatric symptoms. Interestingly, further regression analysis revealed that the interaction between BMI and TAS was associated with the negative symptoms in the early stage of SZ. CONCLUSIONS: Our study indicates that abnormal TAS levels interacting with overweight/obesity may be involved in the pathophysiology of SZ, in particular negative symptoms.

Parental marital status and anxiety symptoms in adolescents: the mediating effect of childhood maltreatment.

Although previous studies have established the association between parental marital status and mental health problems in adolescents, however, the adverse effects of incomplete family settings and childhood maltreatment on adolescent anxiety symptoms have not been fully investigated. Moreover, whether childhood maltreatment can mediate the relationship between parental marital status and anxiety symptoms remains unclear. A population-based cross-sectional study was performed among 35,573 adolescents in elementary schools across 17 provinces in China. And childhood maltreatment, resilience, and anxiety symptoms were assessed among adolescents, respectively. The parental marital status was self-reported as having two married biological parents, divorced parents, stepparents, and single-parent. We found that the rates of anxiety symptoms among adolescents were 35.1% in intact families, 48.8% in divorced families, 49% in stepparent families, and 48% in single-parent families. Divorced parents (aOR = 1.191, 95% CI [1.060-1.337]) was an independent risk factor for adolescents' anxiety symptom while having stepparents and single-parent were not. In addition, emotional abuse (aOR = 1.300, 95% CI [1.285-1.316]), sexual abuse (aOR = 1.088, 95% CI [1.063-1.114]), and physical neglect (aOR = 1.019, 95% CI [1.007-1.031]) were all independent risk factors for anxiety symptoms in adolescents, while physical abuse and emotional neglect were not. The negative impacts of divorced and remarried parents on adolescent anxiety symptoms were mediated by childhood maltreatment partially (64.9% and 72.2%), while childhood maltreatment completely mediated the adverse impacts of single-parent on adolescent anxiety symptoms. Childhood maltreatment intervention strategies could be necessary for anxiety symptoms of adolescents in divorced/stepparent/single-parent families.

Sex-related differences in parental rearing patterns in young adults with bipolar disorder.

The aim of this study was to examine the parenting characteristics of young patients with bipolar disorder (BD) and explore the sex differences. The parental rearing pattern of young patients with BD was measured and compared with the healthy control of young adults. The EMBU scale was used to assess parental rearing patterns. Patients with BD reported significantly higher scores in the punishment and severity index, as well as of the rejection and denial index, but lower scores in the warmth & affectionate index in the paternal rearing pattern, compared with healthy controls. In addition, patients scored higher on the punishment and severity index and rejection and patterns index in maternal rearing patterns. More importantly, we found significant sex differences in maternal rearing patterns (pBonferroni < 0.05). Specifically, in the maternal rearing patterns, male patients had higher scores on the favoring index than male controls, whereas female patients had lower scores on the warmth & affectionate index than female controls. This study shows significant differences in parental rearing patterns between patients and control subjects. Male patients were overprotective by their mothers and female patients were overlooked by their mothers during upbringing.

Grouping motivational interviewing is only effective for younger patients with alcohol dependence in the rehabilitation stage.

Alcohol dependence (AD) is a risk factor for death and disability. Relapse prevention for AD has been exclusively dominated by psychotherapy intervention for many years. Our study aimed to investigate the efficacy of group motivational interviewing (MI) on the psychological craving for alcohol and depressive symptoms in AD patients in the rehabilitation phase, as well as the impact of age. The participants included 108 individuals with AD in the rehabilitation phase. All participants were assigned to the MI intervention group or the control group and were treated for 6 weeks. The severity of psychological craving for alcohol was assessed by the Penn Alcohol Craving Scale (PACS), and psychological status was evaluated by the Hamilton Depression Rating Scale (HAMD). We found that group MI significantly reduced the psychological craving for alcohol in patients with AD in the rehabilitation phase (p < 0.05). In addition, when patients were divided into two groups according to their ages, we found that group MI interventions tended to be effective only in younger patients with AD, but not in older patients. Our findings provide further evidence that the efficacy of group MI interventions was influenced by the age of patients with AD in the rehabilitation stage.

Association of P50 with social function, but not with cognition in patients with first-episode schizophrenia.

Functional deficits including cognitive impairment and social dysfunction are the core symptoms of schizophrenia (SCZ), and sensory gating (SG) deficits may be involved in the pathological mechanism of functional deficits in SCZ. This study was to investigate the relationship between defective P50 inhibition and functional deficits in first-episode drug naïve (FEDN) SCZ patients. A total of 95 FEDN SCZ patients and 53 healthy controls (HC) were recruited. The Chinese version of UCSD Performance-Based Skills (UPSA), MATRICS Consensus Cognitive Battery (MCCB), and EEG system were used to assess the social function, cognitive performance, and P50 inhibition, respectively. The MCCB total score and eight domain scores were significantly lower in patients with FEDN SCZ than those in HC (all p < 0.05). The UPSA total score and financial skills scores were also significantly lower in SCZ patients than that in the HC (all p < 0.05). Compared with HC, patients with FEDF SCZ had a higher P50 ratio (all p < 0.05). There was no correlation between P50 components and MCCB scores in patients with FEDF SCZ. However, there was only a correlation between the P50 ratio and UPSA financial skills, communication skills, or total score in patients (all p < 0.05). Defective P50 inhibition in FEDN SCZ patients may be associated with social dysfunction but not cognitive impairment, suggesting that the social dysfunction and cognitive impairment of patients with FEDN SCZ may have different pathogenic mechanisms.

Diabetes mellitus in patients with chronic bipolar disorder: prevalence, clinical correlates and relationship with homocysteine.

Comorbid diabetes mellitus in patients with bipolar disorder may contribute to increased morbidity and mortality. To determine the prevalence of diabetes mellitus in bipolar disorder patients and its clinico-demographic and homocysteine correlates, we conducted a cross-sectional survey of 195 bipolar disorder inpatients. They received questionnaires, clinical measurements and laboratory tests to assess demographic characteristics, anthropometric variables, clinical variables and plasma homocysteine levels. The prevalence of diabetes mellitus (including type 1, type 2 and special types) in Chinese bipolar disorder patients was 14.9%. Analysis of variance or chi-square test showed that compared with non-diabetic bipolar disorder patients, diabetic bipolar disorder patients were older, more often married, had a longer duration of disease, took less olanzapine and had a higher frequency of hypertension. However, there were no significant differences in body mass index (BMI) and homocysteine levels between diabetic and non-diabetic bipolar disorder patients. Logistic regression analysis showed that marital status and duration of disease were independently associated with diabetes mellitus in patients with bipolar disorder after controlling for age, use of olanzapine, presence of hypertension, BMI and homocysteine levels. These findings shed light on the clinico-demographic correlates of the increased prevalence of diabetes mellitus in bipolar disorder patients, rather than the correlation with some metabolic risk factors.

Baseline BMI is associated with clinical symptom improvements in first-episode schizophrenia: a longitudinal study.

Background: There is sufficient evidence of the high prevalence of obesity in schizophrenia (SZ) compared to the general population. Previous studies have reported that weight gain correlated with the response to antipsychotics in patients with SZ. Nonetheless, the relationship between body mass index (BMI) and therapeutic benefits remains unclear. This study was designed to investigate the association between baseline BMI and improvements in clinical symptoms after treatment with antipsychotics in first-episode and medication-naïve SZ (FEMNS). Methods: A total of 241 FEMNS patients were enrolled and received risperidone over 12 weeks. The severity of symptoms was assessed by the Positive and Negative Syndrome Scale (PANSS) and BMI was measured at baseline and 12-week follow-up. Results: We found that risperidone treatment raised the body weight of FEMNS patients and baseline BMI was negatively correlated with the improvement in negative symptoms (r = -0.14, p = 0.03) after 12-week treatment. Linear regression analysis indicated that baseline BMI was an independent predictor of response to risperidone in the early stage of SZ. Conclusion: The current study suggests a close relationship between baseline BMI and improvement in negative symptoms in SZ.

Smoking, Symptoms Improvement, and Total Antioxidant Capacity in Patients with Drug-naive First-episode Schizophrenia: A Prospective Cohort Study.

BACKGROUND: It has been hypothesized that smoking is associated with the severity of negative symptoms. Until now, no studies have investigated whether the impact of smoking on negative symptoms is dependent on antioxidants. This study was designed to evaluate the effect of smoking on therapeutic response and total antioxidants capacity (TAOC) in antipsychotic-naïve first-episode (ANFE) patients. METHODS: The severity of the patient's symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). A total of 237 ANFE patients were recruited and treated with risperidone (oral tablets, 4-6 mg/day twice a day) for 12 weeks. PANSS was assessed at baseline and a 12-week follow-up. Plasma TAOC levels were also assayed at baseline and week 12. RESULTS: Relative to nonsmokers with ANFE SZ, smokers had higher PANSS negative subscores. There was no significant difference in TAOC changes after 12 weeks of treatment with risperidone between smokers and non-smokers. However, we found greater improvement in negative symptoms in smokers compared to non-smokers. Further analysis in smokers with SZ demonstrated that improvements in negative symptoms were not associated with changes in TAOC. CONCLUSION: Our study suggested that smoking affected the severity of baseline negative symptoms and further contributed to their reduction after risperidone treatment. However, improvement in negative symptoms was not dependent on the changes in TAOC.

Efficacy of standard operating procedures for fall protection in hospitalized patients with schizophrenia.

Fall-related injury is the most common cause of functional disability and mortality in the older population. Falls in patients with schizophrenia are one of the major concerns in psychiatric hospitals. This study aimed to examine the impact of standardized operating procedures (SOP) on falls in veterans with schizophrenia. Veterans with schizophrenia were allocated to the control group (n = 345) and to the fall protection standardized operating procedures (FP-SOP) group (n = 342). Patients in the control group were given routine nursing for falls, and patients in the FP-SOP group were intervened with FP-SOP plus routine nursing. All patients were observed for one year. The study methods comply with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. We found a fall rate of 1.5% in the FP-SOP group and 4.6% in the control group, with a significant difference in the fall rate between the two groups. In addition, the difference in patient satisfaction between the two groups was statistically significant. Our findings suggest that FP-SOP is an effective strategy for fall prevention in psychiatric hospitals.

Sex difference in association between cognitive and P50 deficits in patients with chronic schizophrenia.

A large number of studies have reported that sensory gating disorders represented by P50 inhibition may be involved in the pathophysiological process of schizophrenia. However, few studies have explored the relationship between sensory gating disorders and cognitive dysfunction in patients with schizophrenia. This study aimed to explore sex differences in the relationship between cognitive and P50 deficits in patients with chronic schizophrenia, which has not been reported. A total of 183 chronic schizophrenia patients (128 males and 55 females) and 166 healthy controls (76 males and 90 females) participated in this study. The MATRICS Consensus Cognitive Battery (MCCB) was measured for cognitive function and P50 components for the sensory gating in all participants. The Positive and Negative Syndrome Scales (PANSS) was used to assess the psychopathological symptoms in patients. Female patients performed significantly better than male patients in several cognitive domains of MCCB (all p < 0.01). There were no significant differences in P50 components between male and female patients (all p > 0.05). Further analysis showed that in female patients, latency of S2 was negatively correlated with reasoning and problem-solving domain of MCCB (p < 0.05), and P50 ratio was negatively correlated with social cognition domain of MCCB (p < 0.05). In male patients, there was no any correlation between P50 and cognitive domains of MCCB. Our results suggest that there is a sex difference in the association between P50 deficiency and cognitive impairment in Chinese Han patients with schizophrenia.

A pilot study to examine the association between COX-2 rs5275 polymorphism and the response to repetitive transcranial stimulation in schizophrenia.

High frequency (HF)-rTMS has been shown to improve cognitive functions in patients with schizophrenia (SCZ). This study aimed to investigate whether COX-2 rs5275 variants were associated with cognitive improvements following rTMS treatment in patients with SCZ. Forty-eight hospitalized patients with SCZ were assigned to the neuronavigation HF-rTMS group and 28 patients to the sham group over left DLPFC for 1 month. Cognitive function was evaluated using the repeatable battery for the assessment of neuropsychological status (RBANS) at weeks 0 and 4. COX-2 rs5275 polymorphism was genotyped by a technician. At baseline, C allele carriers showed better cognitive performance relative to patients with TT homozygote. Additionally, C allele carriers had greater improvement in memory from the follow-up to baseline following rTMS stimulation, while patients with the TT genotype showed no significant improvement in memory index. More importantly, we found that COX-2 rs5275 was correlated with the response to rTMS after controlling for the covariates. This study data indicate that COX-2 rs5275 was associated with improvements in immediate memory after HF-rTMS treatment in patients with SCZ. rTMS shows an effect on memory only in C allele carriers, but not in those with the TT genotype.

Efficacy of Low-dose Olanzapine in Combination with Sertraline on Negative Symptoms and Psychosocial Functioning in Schizophrenia: A Randomized Controlled Trial.

BACKGROUND: Evidence for the efficacy of a low dose of olanzapine (OLA) in combination with antidepressants has been limited and without positive trials in first-episode (FE) patients with schizophrenia (SCH). This study aimed to compare the efficacy in treating negative and depressive symptoms between those FE patients with SCH treated with a combination of OLA plus sertraline and those treated with OLA monotherapy. METHODS: One hundred and ninety-six first-episode and drug naïve patients with SCH were randomized to receive low-dose OLA (7.5-10 mg/day) combined with sertraline (50-100 mg/day) (OS group) or normal-dose OLA monotherapy (12.5-20 mg/day) (NO group). Clinical symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS), and the depressive symptoms were evaluated by the Hamilton Depression Scale (HAMD). Psychosocial functioning was assessed by the Personal and Social Performance Scale (PSP). RESULTS: In the intent-to-treat efficacy analysis, the OS group had greater decreases in negative and depressive symptoms (pall < 0.01) and a greater increase in PSP total score compared with the NO group (p < 0.01). Moreover, reductions in HAMD total score and PANSS negative subscore and sex were associated with the improvements in psychosocial functioning from baseline to week 24, after controlling for baseline psychosocial function, age, and onset age. CONCLUSION: This study demonstrates that low-dose OLA in combination with sertraline had clinically meaningful improvements not only in the negative and depressive symptoms but also in psychosocial functioning in patients with FE-SCH, while not affecting positive symptoms.

Association between cognitive function and IL-18 levels in schizophrenia: Dependent on IL18 - 607 A/C polymorphism.

Accumulating evidence suggests that immune system dysregulation is associated with debilitating neurodevelopment in schizophrenia (SZ). Cognitive impairment is a persistent feature that occurs during the onset of SZ and persists throughout the course of the disease. Early studies have found that elevated interleukin (IL)- 18 interacts with IL18 polymorphism and is correlated with psychotic symptoms in SZ. This study aimed to investigate whether elevated IL-18 levels interacted with the -607 A/C polymorphism to determine cognitive decline in patients with chronic SZ. We recruited 693 inpatients and 422 healthy controls to measure IL-18 levels and genotype the - 607 A/C polymorphism. Further, cognitive function was measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). We found that IL-18 serum levels were higher in patients than those in healthy controls, and were not associated with IL18 - 607 A/C in combined subjects or either patients or healthy controls, respectively. Moreover, - 607 A/C was correlated with the visuospatial/constructional index only in the patients. In addition, our research found that IL-18 levels were positively correlated to immediate memory only in patients with the C/C genotype, but not in patients with C/A or A/A genotype. This study suggests that the relationship of IL-18 with cognitive function depends on the IL18 - 607 A/C polymorphism of SZ patients.