Smoking affects symptom improvement in schizophrenia: a prospective longitudinal study of male patients with first-episode schizophrenia.

Patients with schizophrenia (SCZ) smoke up to three times more than general people. However, there are conflicting results regarding the relationship between tobacco smoke and clinical symptom severity in SCZ. The aim of this study was to assess the impact of smoking on clinical symptoms after antipsychotic treatment in a 12-week cohort study after controlling for confounding factors. One hundred and forty-five male patients with drug-naïve first-episode (DNFE) SCZ received antipsychotic monotherapy for 12 weeks. Symptom severity was assessed at baseline and at week 12 by the Positive and Negative Syndrome Scale (PANSS). We found no differences in clinical symptoms among male smokers with SCZ compared with male nonsmokers. However, male smokers showed greater improvement in negative symptoms after 12 weeks of treatment, controlling for age, years of education, onset age, and baseline body mass index (BMI). Our study showed that after 12 weeks of treatment with antipsychotics, male smokers showed greater improvement in negative symptoms than male nonsmokers.

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.

Effect of Repetitive Transcranial Magnetic Stimulation in Inducing Weight Loss in Patients with Chronic Schizophrenia: A Randomized, Double-Blind Controlled 4-Week Study.

OBJECTIVES: There is emerging evidence that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) may promote weight loss in individuals with obesity in the general population. However, no study has been conducted on patients with schizophrenia (SZ). This study evaluated the efficacy of 10Hz rTMS in reducing body weight in patients with chronic SZ. METHODS: Forty-seven SZ patients were randomly assigned to two groups: 10Hz rTMS or sham stimulation over DLPFC (applied once daily) for 20 consecutive treatments. Body weight was assessed at baseline, at the end of week 1, week 2, week 3 and week 4. Clinical symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS) at baseline and at the end of week 4. RESULTS: We found that compared with patients in the sham group, 10Hz rTMS treatment significantly reduced body weight in patients with chronic SZ after a period of 4 weeks of stimulation. Interestingly, further analysis found that from the first week (5 sessions) of treatment, there was a significant difference in body weight between active and sham groups after controlling for baseline weight. However, active rTMS treatment did not improve the psychotic symptoms compared to sham stimulation. CONCLUSION: Our results suggest that add-on HF rTMS could be an effective therapeutic strategy for body weight control in patients with chronic SZ.

Neuronavigated Repetitive Transcranial Stimulation Improves Neurocognitive Functioning in Veterans with Schizophrenia: A Possible Role of BDNF Polymorphism.

It has been reported in the previous literatures that high-frequency (HF) neuronavigated repetitive transcranial magnetic stimulation (rTMS) may improve neurocognitive functioning in patients with schizophrenia. Nonetheless, the heterogeneity of the research findings with regards to the effectiveness of HF-rTMS on the neurocognitive functioning in patients with schizophrenia greatly hinders its clinical application. The current study was designed to determine the predictive role of BDNF variants for neurocognitive improvements after rTMS administration in veterans with schizophrenia. 109 hospitalized veterans with schizophrenia were randomly allocated to active HF-rTMS (n=63) or sham stimulation (n=46) over left DLPFC for 4 consecutive weeks. Neurocognitive functions were assessed by using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) at baseline and at the end of week 4. BDNF polymorphism was genotyped by the technicians. Compared with sham stimulation sessions, the immediate memory performance was significantly increased in active sessions after neuronavigated HF-rTMS administration. In addition, patients with the CC homozygotes demonstrated greater improvement of immediate memory after rTMS treatment, while T allele carriers showed no significant improvement in immediate memory domain relative to baseline performance of immediate memory. Our findings suggest that add-on neuronavigated HF-rTMS is beneficial on immediate memory only in patients with CC homozygotes, but not in T allele carriers. This pilot study provides further evidence for BDNF as a promise biomarker in predicting the clinical response to rTMS stimulation.

Repetitive transcranial magnetic stimulation for psychiatric symptoms in long-term hospitalized veterans with schizophrenia: A randomized double-blind controlled trial.

Multiple lines of evidence demonstrate that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) may improve clinical outcomes in patients with schizophrenia (SCZ). However, the efficacy of HF-rTMS on psychiatric symptoms remains unknown in veterans with SCZ. This study aimed to investigate whether HF-rTMS was beneficial in alleviating the clinical symptoms in veterans with SCZ. Forty-seven long-term hospitalized veterans with SCZ were randomly allocated to receive neuronavigated 10 Hz rTMS or sham stimulation over the left dorsolateral prefrontal cortex once daily for four consecutive weeks. Symptoms were assessed by using the Positive and Negative Syndrome Scale at baseline and at the end of week 4. We also collected easily available routine biochemical markers including blood sugar, lipid profiles, hormone, and blood cell counts, considering that these markers may potentially be used to predict the outcomes of rTMS treatment. We found that there was a significant interaction effect of time and group on the positive symptoms. Compared with the sham group, the positive factor score of veterans with SCZ was significantly decreased after treatment in the real rTMS group. Interestingly, the improvement of positive symptoms from baseline to 4-week follow-up was significantly associated with the whole white blood cells (WBC) counts at baseline in the real rTMS group, and baseline WBC counts were predictive of the symptom improvement after rTMS treatment. Our findings indicate that add-on 10 Hz rTMS is beneficial for clinical symptoms in veterans with SCZ. In addition, the baseline WBC counts were predictive of the outcomes after treatment. Clinical trial registration: clinicaltrials.gov, identifier NCT03774927.

Plasma linoelaidyl carnitine levels positively correlated with symptom improvement in olanzapine-treated first-episode drug-naïve schizophrenia.

INTRODUCTION: Olanzapine (OLA) is one of the most commonly used second-generation antipsychotics for the treatment of schizophrenia. However, the heterogeneity of therapeutic response to OLA among schizophrenia patients deserves further exploration. The role of carnitine in the clinical response to OLA monotherapy remains unclear. OBJECTIVES: The current study was designed to investigate whether carnitine and its derivatives are linked to the response to OLA treatment. Drug-naïve first-episode patients with schizophrenia were recruited and treated with OLA for 4 weeks. Psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) in pre and post treatment. RESULTS: After treatment, we found a significant decrease in 2-Octenoylcarnitine levels and a significant increase in linoelaidyl carnitine, 11Z-Octadecenylcarnitine and 9-Decenoylcarnitine levels. Furthermore, baseline linoelaidyl carnitine levels were correlated with the reduction of PANSS positive symptom subscore. Linear regression and logistic regression analyses found that the baseline linoelaidyl carnitine level was a predictive marker for the therapeutic response to OLA monotherapy for 4 weeks. CONCLUSION: Our pilot study suggests that linoelaidyl carnitine levels at baseline may have a predictive role for the improvement of positive symptoms after OLA monotherapy in the patients with schizophrenia.

Association between Changes in Total Antioxidant Levels and Clinical Symptom Improvement in Patients with Antipsychotic-Naïve First-Episode Schizophrenia after 3 Months of Risperidone Monotherapy.

Schizophrenia (SCZ) is associated with aberrant redox regulation in the early stages of brain development. There is growing evidence that the antioxidant defense system is closely associated with the therapeutic response to antipsychotics in SCZ patients. The aim of this study was to examine the effect of risperidone monotherapy on total antioxidant status (TAS) and the relationship between symptom improvement and changes in TAS in patients with antipsychotic-naïve first-episode (ANFE) SCZ. Clinical symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Two hundred and forty-six ANFE patients were treated with risperidone for 3 months. PANSS and TAS levels were assessed at baseline and at a 3-month follow-up. Relative to healthy controls, ANFE patients had higher TAS levels, which increased even further during the treatment. Moreover, baseline TAS levels were a predictor of symptom reduction after risperidone treatment. In addition, there was a significant association between increased TAS levels and the decreased cognitive factor. Our findings suggest that antioxidant protection is possibly associated with clinical improvement in ANFE patients after risperidone treatment.

Genetic polymorphisms of BDNF on cognitive functions in drug-naive first episode patients with schizophrenia.

Brain-derived neurotrophic factor (BDNF) is reported to be involved in cognitive decline in patients with schizophrenia (SZ). Previous studies have found that cognitive deficits remain stable during the chronic disease phase in SZ, but the findings were inconsistent. The role of BDNF in cognitive deficits at different stage of illness remains unclear. This study aimed to examine the effect of BDNF polymorphisms on cognitive deficits in drug-naïve first-episode (DNFE) patients and chronic patients with SZ. 262 DNFE patients, 844 chronic patients, and 1043 healthy controls were recruited to compare 4 polymorphisms in BDNF gene and cognitive function. We found that there was no significant difference in genotype and allele frequencies between SZ patients and controls. However, they were closely related to cognitive functioning. BDNF rs2030324 polymorphism played a strong role in language performance only in DNFE patients with SZ. The language index of DNFE patients with rs2030324 TT and TC genotypes was worse than that of chronic patients, but there was no significant difference in CC genotypes between DNFE and chronic patients. Rs6265 had no significant effect on cognitive functioning in patients and controls. Our result suggests BDNF gene polymorphisms were related to different domains of cognitive function at the different stage of SZ, especially language in DNFE patients.

Identifying clinical risk factors correlate with suicide attempts in patients with first episode major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is the most common mental disorder associated with suicide attempts. When a patient first visits the clinic, clinicians are often expected to make concrete diagnose about acute suicidal risk. However, the timeliness of suicide attempts correlates with patients with MDD has not been tested. METHODS: We divided 1718 first-episode and untreated MDD outpatients into those who did not have suicide attempts (non-attempts), recent suicide attempters (≤14 days before assessment) and long - dated suicide attempters (> 30 days before assessment). Positive Symptom Scale of Positive and Negative Syndrome Scale (PANSS), the 17-item Hamilton Depression Scale, 14 - item Hamilton Anxiety Scale, and clinical global impression of severity scale (CGI-S) was assessed. Body mass index, some glycolipid metabolism and thyroid hormone parameters were measured. A gradient-boosted decision trees statistical model was used to generate equally weighted classification for distinguishing recent and long - dated suicide attempters from non-attempts. RESULTS: The classifier identified higher excitement, hostility, anxiety, depression symptoms and higher free thyroxine (FT4) as risk factors for recent suicide attempters with an estimated accuracy of 87% (sensitivity, 59.1%; specificity, 61.2 %). For long - dated suicide attempters' risk factors, single status, higher anxiety and hostility symptoms, higher LDLC and lower BMI, the estimated accuracy was 88% (sensitivity, 52.8%; specificity, 49.6%). CONCLUSIONS: Risk factors for suicide attempt among patients with MDD can be identified by integrating demographic, clinical, and biological variables as early as possible during the first time see a doctor.