Smoking Rates and Number of Cigarettes Smoked per Day in Schizophrenia: A Large Cohort Meta-Analysis in a Japanese Population.

Background: Cigarette smoking is consistently more common among schizophrenia patients than the general population worldwide; however, the findings of studies in Japan are inconsistent. Recently, the smoking rate has gradually decreased among the general population. Methods: We performed a meta-analysis of smoking status in a large Japanese cohort of (1) 1845 schizophrenia patients and 196845 general population and (2) 842 schizophrenia patients and 766 psychiatrically healthy controls from 12 studies over a 25-year period, including 301 patients and 131 controls from our study. Results: In our case-control sample, schizophrenia patients had a significantly higher smoking rate than healthy controls (P=.031). The proportion of heavy smokers (P=.027) and the number of cigarettes smoked per day (P=8.20×10-3) were significantly higher among schizophrenia patients than healthy controls. For the smokers in the schizophrenia group, atypical antipsychotics dosage was positively correlated with cigarettes per day (P=1.00×10-3). A meta-analysis found that schizophrenia patients had a higher smoking rate than the general population for both men (OR=1.53, P=.035; schizophrenia patients, 52.9%; general population, 40.1%) and women (OR=2.40, P=1.08×10-5; schizophrenia patients, 24.4%; general population, 11.8%). In addition, male schizophrenia patients had a higher smoking rate than male healthy controls (OR=2.84, P=9.48×10-3; schizophrenia patients, 53.6%; healthy controls, 32.9%), but the difference was not significant for women (OR=1.36, P=.53; schizophrenia patients, 17.0%; healthy controls,14.1%). Among both males and females, schizophrenia patients had a higher smoking rate than both the general population (OR=1.88, P=2.60×10-5) and healthy controls (OR=2.05, P=.018). These rates were not affected by the patients' recruitment year (P>.05). The cigarettes per day values of schizophrenia patients and the general population were 22.0 and 18.8, respectively. Conclusions: Schizophrenia patients are approximately 2 times more likely to smoke than the general population and healthy controls based on data collected over a decade in Japan.

Meta-analysis of physical activity and effects of social function and quality of life on the physical activity in patients with schizophrenia.

Schizophrenia patients have increased mortality and morbidity, mainly due to premature cardiovascular disease resulting from decreased physical activity (PA). However, which PA intensity is impaired in the patients and how factors such as social function and quality of life (QoL) are related to decreased PA is unknown. To assess PA, social function and QoL, the International Physical Activity Questionnaire (IPAQ), Social Functioning Scale (SFS) and Schizophrenia Quality of Life Scale (SQLS), respectively, were used in 109 schizophrenia patients and 69 healthy subjects. A meta-analysis comparing PA intensities (vigorous, moderate and light) assessed by the single PA measurement between schizophrenia patients and healthy subjects after including our case-control sample was performed. Furthermore, the effects of social function and QoL on each level of PA intensity were investigated in patients and controls. The meta-analysis in 212 schizophrenia patients and 132 healthy subjects revealed that patients showed lower total PA, particularly vigorous PA, than controls (I2 = 0, Hedges' g = - 0.41, P = 2.80 × 10-4). The decreased total PA was correlated with impaired total SFS scores (ß = 0.24, P = 2.86 × 10-3), withdrawal (ß = 0.23, P = 3.74 × 10-3) and recreation (ß = 0.23, P = 3.49 × 10-3) without significant heterogeneity between patients and controls. In contrast, the decreased total PA was affected by low independence-performance (ß = 0.22, P = 0.034), employment/occupation (ß = 0.27, P = 8.74 × 10-3), psychosocial (ß = - 0.24, P = 0.021) and motivation/energy (ß = - 0.26, P = 0.013), but only in patients. Similar findings were obtained for vigorous PA but not moderate or light PA. Our findings suggest that the impaired vigorous PA in schizophrenia patients may be mediated by schizophrenia-specific factors of social functioning and QoL. Understanding these factors has important implications for increasing PA participation in schizophrenia patients.

Genome-Wide Variants Shared Between Smoking Quantity and Schizophrenia on 15q25 Are Associated With CHRNA5 Expression in the Brain.

Cigarette smokers with schizophrenia consume more cigarettes than smokers in the general population. Schizophrenia and smoking quantity may have shared genetic liability. Genome-wide association studies (GWASs) of schizophrenia and smoking quantity have highlighted a biological pleiotropy in which a robust 15q25 locus affects both traits. To identify the genetic variants shared between these traits on 15q25, we used summary statistics from large-scale GWAS meta-analyses of schizophrenia in the Psychiatric Genomics Consortium 2 and smoking quantity assessed by cigarettes smoked per day in the Tobacco and Genetics Consortium. To evaluate the regulatory potential of the shared genetic variants, expression quantitative trait loci analysis in 10 postmortem brain regions was performed using the BRAINEAC dataset in 134 neuropathologically normal individuals. Twenty-two genetic variants on 15q25 were associated with both smoking quantity and schizophrenia at the genome-wide significance level (P < 5.00 × 10-8). Major alleles of all variants were associated with higher smoking quantity and risk of schizophrenia. These genetic variants were associated with PSMA4, CHRNA3, and CHRNB4 expression in specific brain regions (lowest P = 4.81 × 10-4) and with CHRNA5 expression in multiple brain regions (lowest P = 8.70 × 10-6). Risk-associated major alleles of these variants were commonly associated with higher expression in several brain regions, excluding the medulla, at the transcript level. In addition, the risk-associated major allele at rs637137 was associated with higher CHRNA5 expression at the specific exon level in multiple brain regions (lowest P = 2.37 × 10-5). Our findings suggest that genome-wide variants shared between smoking quantity and schizophrenia contribute to a common pathophysiology underlying these traits involving altered CHRNA5 expression in the brain.

Response to benzodiazepines and the clinical course in malignant catatonia associated with schizophrenia: A case report.

BACKGROUND: Malignant catatonia (MC) is a disorder consisting of catatonic symptoms, hyperthermia, autonomic instability, and altered mental status. Neuroleptic malignant syndrome (NMS) caused by antipsychotics is considered a variant of MC. Benzodiazepine (BZD) medications are safe and effective treatments providing rapid relief from MC. This case study reports a detailed clinical course of a case of MC associated with schizophrenia initially diagnosed as NMS that responded successfully to BZDs but not to dantrolene. CASE PRESENTATION: A 53-year-old man with schizophrenia was admitted to the psychiatric hospital because of excitement, monologue, muscle rigidity, and insomnia. In the 3 days before admission, the patient had discontinued his medications after his family member's death. He presented with hyperthermia, tachycardia, hypertension, excessive sweating, and an elevated serum creatine phosphokinase (CPK) level. On the basis of these features, he was suspected to have NMS. The patient was treated with dantrolene for 7 days without improvement despite having a normalized serum CPK level. The patient was transferred to our university hospital for an in-depth examination and treatment of his physical status. Infection and pulmonary embolism were excluded as possible causes. To treat his excitement and auditory hallucination, an intravenous drip (IVD) of haloperidol was initiated, but this treatment increased the patient's catatonic and psychotic symptoms, although his serum CPK level had remained within a normal range. As a result, the treatment was changed to diazepam. After an IVD of diazepam, the patient's symptoms rapidly improved, and the IVD was subsequently replaced with oral administration of lorazepam. Eventually, the patient was diagnosed with MC associated with schizophrenia. BZD therapy was dramatically effective. CONCLUSION: Catatonia, MNS, and MC may be due to a common brain pathophysiology and these conditions may be in a spectrum, although uncertainty in the boundaries among conditions, and the BZD treatment may be useful. Most importantly, catatonia has not been described as a subtype of schizophrenia on the basis of the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria, and the medications for catatonia and schizophrenia are different. Antipsychotics are not effective in relieving catatonia, or they may induce NMS, whereas BZDs are effective for treating both MC and NMS.