Acute effects of low-intensity one-legged electrical muscle stimulation on arterial stiffness in experimental and control limbs.

The aim of this study was to examine the acute effects of low-intensity one-legged electrical muscle stimulation (EMS) for skeletal muscle on arterial stiffness in EMS and non-EMS legs. Eighteen healthy subjects received two different protocols (Control (CT) and Experimental (ET) trials) in random order on separate days. EMS was applied to the left lower limb at 4 Hz for 20 min at an intensity corresponding to an elevation in pulse rate of approximately 15 beats/min (10.9 ± 5.1% of heart rate reserve). Before and after the experiment, arterial stiffness parameters in the control right leg (CRL) and control left leg (CLL) in CT and non-EMS leg (NEL) and EMS leg (EL) in ET were assessed by pulse wave velocity (baPWV, faPWV) and cardio-ankle vascular index (CAVI). No significant changes in all parameters were observed in either leg in CT. Conversely, in ET, low-intensity, single-leg EMS significantly reduced CAVI, baPWV, and faPWV in the EL, but not in the NEL. Acute, low-intensity single-leg EMS reduces arterial stiffness only in the EL. These data support our idea that physical movement-related regional factors rather than systematic factors are important for inducing acute reductions in arterial stiffness.

The neuromodulatory role of dopamine in improved reaction time by acute cardiovascular exercise.

Acute cardiovascular physical exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Here, using positron emission tomography (PET) with [11 C]raclopride, in a multi-experiment study we investigated whether acute exercise releases endogenous dopamine (DA) in the brain. We hypothesized that acute exercise augments the brain DA system, and that RT improvement is correlated with this endogenous DA release. The PET study (Experiment 1: n = 16) demonstrated that acute physical exercise released endogenous DA, and that endogenous DA release was correlated with improvements in RT of the Go/No-Go task. Thereafter, using two electrical muscle stimulation (EMS) studies (Experiments 2 and 3: n = 18 and 22 respectively), we investigated what triggers RT improvement. The EMS studies indicated that EMS with moderate arm cranking improved RT, but RT was not improved following EMS alone or EMS combined with no load arm cranking. The novel mechanistic findings from these experiments are: (1) endogenous DA appears to be an important neuromodulator for RT improvement and (2) RT is only altered when exercise is associated with central signals from higher brain centres. Our findings explain how humans rapidly alter their behaviour using neuromodulatory systems and have significant implications for promotion of cognitive health. KEY POINTS: Acute cardiovascular exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Using the neurochemical specificity of [11 C]raclopride positron emission tomography, we demonstrated that acute supine cycling released endogenous dopamine (DA), and that this release was correlated with improved RT. Additional electrical muscle stimulation studies demonstrated that peripherally driven muscle contractions (i.e. exercise) were insufficient to improve RT. The current study suggests that endogenous DA is an important neuromodulator for RT improvement, and that RT is only altered when exercise is associated with central signals from higher brain centres.

Differences in autonomic nervous system activity between long-acting injectable aripiprazole and oral aripiprazole in schizophrenia.

BACKGROUND: Distinct oral atypical antipsychotics have different effects on autonomic nervous system (ANS) activity. Among them, oral aripiprazole has been linked to dysfunction of the ANS in schizophrenia. Long-acting injectable aripiprazole is a major treatment option for schizophrenia, but the effect of the aripiprazole formulation on ANS activity remains unclear. In this study, we compared ANS activity between oral aripiprazole and aripiprazole once-monthly (AOM) in schizophrenia. METHODS: Of the 122 patients with schizophrenia who participated in this study, 72 received oral aripiprazole and 50 received AOM as monotherapy. We used power spectral analysis of heart rate variability to assess ANS activity. RESULTS: Patients who received oral aripiprazole showed significantly diminished sympathetic nervous activity compared with those who received AOM. Multiple regression analysis revealed that the aripiprazole formulation significantly influenced sympathetic nervous activity. CONCLUSION: Compared with oral aripiprazole, AOM appears to have fewer adverse effects, such as sympathetic nervous dysfunction.

Acute Effects of Low-Intensity Electrical Stimulation on Segmental Arterial Stiffness.

Electrical muscle stimulation (EMS) has traditionally been employed to improve muscle strength and glucose uptake. EMS may also reduce arterial stiffness, but little is known about whether low-intensity EMS reduces systemic and/or regional arterial stiffness. This study aimed to examine the effects of low-intensity EMS of the lower limbs on segmental arterial stiffness. Fourteen healthy subjects participated in experiments under two different protocols (control resting trial (CT) and electrical stimulation trial (ET)) in random order on separate days. The EMS was applied to the lower limbs at 4 Hz for 20 min at an intensity corresponding to an elevation of approximately 15 beats/min in pulse rate (10.7 ± 4.7% of heart rate reserve). Arterial stiffness was assessed by cardio-ankle vascular index (CAVI), CAVI0, heart-ankle pulse wave velocity (haPWV), brachial-ankle pulse wave velocity (baPWV), heart-brachial pulse wave velocity (hbPWV), and carotid-femoral pulse wave velocity (cfPWV). In both trials, each parameter was measured at before (Pre) and 5 min (Post 1) and 30 min (Post 2) after trial. After the experiment, CT did not cause significant changes in any arterial stiffness parameters, whereas ET significantly reduced CAVI (from Pre to Post 1: -0.8 ± 0.5 unit p < 0.01), CAVI0 (from Pre to Post 1: -1.2 ± 0.8 unit p < 0.01), haPWV (from Pre to Post 1: -47 ± 35 cm/s p < 0.01), and baPWV (from Pre to Post 1: -120 ± 63 cm/s p < 0.01), but not hbPWV or cfPWV. Arm diastolic blood pressure (BP) at Post 2 was slightly but significantly increased in the CT compared to Pre or Post 1, but not in the ET. Conversely, ankle diastolic and mean BPs at Post 1 were significantly reduced compared to Pre and Post 2 in the ET (p < 0.01). These findings suggest that low-intensity EMS of the lower limbs reduces arterial stiffness, but only in sites that received EMS.

Effects of electrical muscle stimulation on cerebral blood flow.

BACKGROUND: Electrical muscle stimulation (EMS) induces involuntary muscle contraction. Several studies have suggested that EMS has the potential to be an alternative method of voluntary exercise; however, its effects on cerebral blood flow (CBF) when applied to large lower limb muscles are poorly understood. Thus, the purpose of this study was to examine the effects of EMS on CBF, focusing on whether the effects differ between the internal carotid (ICA) and vertebral (VA) arteries. METHODS: The participants performed the experiments under EMS and control (rest) conditions in a randomized crossover design. The ICA and VA blood flow were measured before and during EMS or control. Heart rate, blood pressure, minute ventilation, oxygen uptake, and end-tidal partial pressure of carbon dioxide (PETCO2) were monitored and measured as well. RESULTS: The ICA blood flow increased during EMS [Pre: 330 ± 69 mL min-1; EMS: 371 ± 81 mL min-1, P = 0.001, effect size (Cohen's d) = 0.55]. In contrast, the VA blood flow did not change during EMS (Pre: 125 ± 47 mL min-1; EMS: 130 ± 45 mL min-1, P = 0.26, effect size = 0.12). In the EMS condition, there was a significant positive linear correlation between ΔPETCO2 and ΔICA blood flow (R = 0.74, P = 0.02). No relationships were observed between ΔPETCO2 and ΔVA blood flow (linear: R = - 0.17, P = 0.66; quadratic: R = 0.43, P = 0.55). CONCLUSIONS: The present results indicate that EMS increased ICA blood flow but not VA blood flow, suggesting that the effects of EMS on cerebral perfusion differ between anterior and posterior cerebral circulation, primarily due to the differences in cerebrovascular response to CO2.

The Hepcidin-25/Ferritin Ratio Is Increased in University Rugby Players with Lower Fat Mass.

Hepcidin-25 is suggested as a surrogate iron status marker in athletes who show exercise-induced anemia; however, the implications of hepcidin concentration in this population remain poorly understood. This study aimed to investigate the relationship between hepcidin and body fat levels in rugby football players. We included 40 male university rugby football players (RUG) and 40 non-athlete controls. All participants underwent an anthropometric analysis and blood testing that included both hepcidin-25 and ferritin levels. The hepcidin-25 level was slightly (11.6%, p = 0.50) higher, and the ferritin level was significantly (35.9%, p < 0.05) lower, in the RUG group than in controls. The hepcidin-25 to-ferritin ratio was significantly higher (62.5%, p < 0.05) in the RUG group. While significant U-shaped correlations were observed between the body fat and ferritin levels in both groups, the correlations between the hepcidin levels and fat mass index were significantly higher in the RUG group (RUG: r = 0.79, controls: r = 0.45). Notably, the RUG with the lower fat mass index group had a higher hepcidin-25 level, lower ferritin level, and then significantly higher hepcidin-25/ferritin ratio. The hepcidin-25/ferritin ratio may serve as a biomarker for iron status in RUG, especially RUG with lower fat mass.

Altered Fecal Microbiotas and Organic Acid Concentrations Indicate Possible Gut Dysbiosis in University Rugby Players: An Observational Study.

Gut eubiosis is essential for the host's health. In athletes, the gut microbiota can be altered by several factors, including diets. While eubiotic gut microbiota in elite rugby players has been reported, our survey found that university rugby players suffered from loose stools and frequent urgency to defecate. To establish the causes of the condition, the microbiota and the concentrations of organic acids in fecal samples of university male rugby players (URP) were analyzed and compared with those of age-matching, non-rugby playing males (control). Body mass indices were significantly (p < 0.05) different between groups. Chao1 index was significant (p < 0.05) lower in URP than in control. The relative abundances of phyla Firmicutes and Bacteroidetes were significantly (p < 0.05) higher and lower, respectively, in URP than in control. Potential pathobiont genera Collinsella, Enterobacter, and Haemophilus were significantly (p < 0.05) abundant, whereas beneficial Akkermansia was lower (p < 0.05) in URP than in control. Succinate, a potential causative of gut inflammation, was five-fold higher in URP than in controls. Our findings all but confirmed that the dysbiotic status of gut in URP.

Comparisons Between Serum Levels of Hepcidin and Leptin in Male College-Level Endurance Runners and Sprinters.

Background: Hepcidin-25 is a 25 amino acid hepatokine and a key regulator of iron metabolism related to iron deficiency anemia. Recent studies have suggested that an elevated hepcidin level is correlated with low energy availability. Leptin is an appetite-suppressing adipokine and has been reported to stimulate hepcidin production in animals and cultured cells. While leptin is modulated by exercise, it is known that endurance runners and sprinters practice different types of exercise. This study investigated and compared the relationships between hepcidin and leptin levels, iron status, and body fat to understand better the risk of iron deficiency anemia in endurance runners and sprinters. Methods: Thirty-six male college track and field athletes (15 endurance runners and 21 sprinters) were recruited for this study. Dietary intake, body composition, and blood levels of ferritin, hepcidin-25, leptin, and adiponectin were measured. Correlations between hepcidin levels and ferritin, body fat, leptin, and adiponectin were evaluated using Pearson's correlation coefficient for each group. Results: The endurance runners had lower hepcidin levels and higher leptin and adiponectin levels compared with sprinters. Ferritin was positively correlated with hepcidin-25 levels in both the endurance and sprinter groups. A positive correlation was observed between hepcidin-25 and body fat or leptin levels only in sprinters. Conclusion: This is the first study investigating the relationship between blood levels of hepcidin and leptin in athletes. The positive correlation between hepcidin-25 and leptin was observed in sprinters but not endurance runners.

The association of genetic polymorphisms in CYP1A2, UGT1A4, and ABCB1 with autonomic nervous system dysfunction in schizophrenia patients treated with olanzapine.

BACKGROUND: Use of the antipsychotic drug olanzapine by patients with schizophrenia is associated with autonomic nervous system (ANS) dysfunction. It is presumed that there are interindividual differences in ANS dysfunction that correspond to pharmacogenetics. In this study, we investigated whether genetic polymorphisms in ABCB1, CYP1A2, and UGT1A4 are associated with this observed ANS dysfunction. METHODS: A total of 91 schizophrenia patients treated with olanzapine monotherapy participated in this study. A power spectral analysis of heart rate variability was used to assess ANS activity. The TaqMan system was used to genotype seven single nucleotide polymorphisms (SNPs) in CYP1A2 (rs2069514 and rs762551), UGT1A4 (rs2011425), and ABCB1 (rs1045642, rs1128503, rs2032582, rs2235048). RESULTS: Sympathetic nervous activity was significantly higher in individuals with the UGT1A4 rs2011425 G allele than in those with the UGT1A4 rs2011425 non-G allele (sympathetic activity, p = .001). Furthermore, sympathetic nervous activity was also significantly associated with UGT1A4 rs2011425 genotype as revealed by multiple regression analysis (sympathetic activity, p = .008). CONCLUSIONS: We suggest that the UGT1A4 rs2011425 polymorphism affects olanzapine tolerability because it is associated with the observed side effects of olanzapine in schizophrenia patients, namely sympathetic dysfunction.

A return to work program improves parasympathetic activity and psychiatric symptoms in workers on sick leave due to depression.

BACKGROUND: People with depression have autonomic function disturbances. In Japan, workers who take leave due to depression often undergo a work-focused intervention program called the return to work (RTW) program at a mental health hospital during their leave of absence. However, its biological efficacy remains unclear. We investigated the biological efficacy of the RTW program, including changes in autonomic nervous system (ANS) activity, in workers on sick leave due to depression in Japan. METHODS: The study involved 104 workers on sick leave due to major depressive disorder or bipolar disorder who underwent the RTW program for 3 months in Yokohama City University Hospital. The ANS activity of all patients was evaluated using heart rate variability at the beginning and end of the 3-month RTW program. Psychiatric symptoms were evaluated using the Montgomery-Åsberg Depression Rating Scale-Japanese (MADRS-J) and Social Adaptation Self-evaluation Scale (SASS). We followed up 3 months after the end of the program and investigated the association between the success in returning to work within 3 months after the end of the RTW program and several factors, including ANS activity, depressive symptoms, and demographic factors. RESULTS: Parasympathetic activity was significantly higher and depressive symptom severity was significantly lower at program end than at baseline. Logistic regression analysis showed that the change in depressive symptoms was significantly associated with success in returning to work. CONCLUSION: We suggest that the RTW program improves parasympathetic activity as well as psychiatric symptoms. ANS activity was not a predictor of a successful return to work within 3 months after the end of the program in workers on sick leave due to depression, but further studies with a larger sample size are needed.

Effects of long-acting injectable antipsychotics versus oral antipsychotics on autonomic nervous system activity in schizophrenic patients.

OBJECTIVE: Long-acting injections (LAIs) of antipsychotics show distinct pharmacokinetic profiles from oral antipsychotics (OAPs). Although there may be differences in adverse event frequency, any differences in their effects on autonomic nervous system (ANS) remain unclear. PATIENTS AND METHODS: In total, 270 schizophrenic patients were recruited in this study: 241 received OAPs (risperidone, olanzapine, quetiapine, or aripiprazole) and 29 received LAIs (risperidone LAI, aripiprazole LAI, or paliperidone palmitate) as monotherapy. Heart rate variability was measured as an index of ANS activity, and the low-frequency (0.03-0.15 Hz) component, high-frequency (0.15-0.40 Hz) component, and total power (0.03-0.40 Hz) were calculated. Components were compared between the groups using t-tests. RESULTS: A significant difference was detected in the low-frequency component between the OAP and LAI groups (P=0.046). No significant difference was found in total power or the high-frequency component between the two groups. CONCLUSION: Compared with OAPs, LAIs have fewer adverse effects on ANS activity, particularly the low-frequency component, as determined using a spectral analysis of heart rate variability.

Association between dysfunction of autonomic nervous system activity and mortality in schizophrenia.

BACKGROUND: Patients with schizophrenia have a higher mortality risk than the general population. Additionally, the autonomic nervous system (ANS) activity of patients with schizophrenia is lower and more dysfunctional than that of the general population. Nonetheless, the association between ANS dysfunction and mortality in schizophrenia is unclear. The aim of this study was to investigate the association between ANS activity and mortality in schizophrenia and to evaluate the predictive values of heart rate variability for long-term survival. METHODS: This study involves the 10-year follow-up of a sample population consisting of 59 Japanese inpatients with schizophrenia between 60 and 70 years of age from 2007 to 2016. The ANS activity of all patients was evaluated using heart rate variability in 2007. RESULTS: Fifty-three participants could be followed up because they stayed in the hospital during the follow-up period. Of these patients, 11 died during follow-up. Their mean age at death was 70.55 ±â€¯3.45 years. The parasympathetic activity of nonsurvivors was significantly lower than that of survivors, and multiple logistic regression analysis showed a significant association between death and parasympathetic activity. CONCLUSION: We suggest that decreased parasympathetic activity could be associated with 10-year all-cause mortality in older schizophrenic patients.

Effects of ABCB1 gene polymorphisms on autonomic nervous system activity during atypical antipsychotic treatment in schizophrenia.

BACKGROUND: There are interindividual differences in the adverse effects of atypical antipsychotics, which include autonomic nervous system (ANS) dysfunction. Accordingly, to clarify the interindividual differences in the adverse effects of specific atypical antipsychotics in schizophrenia, we investigated the association between ANS dysfunction and ATP-binding cassette transport sub-family B member 1 (ABCB1) gene polymorphisms in patients with schizophrenia. METHODS: In total, 233 Japanese patients with schizophrenia participated in this study. All of the participants received an atypical antipsychotic as monotherapy: 89 participants received risperidone, 69 olanzapine, 48 aripiprazole, and 27 quetiapine. ANS activity was assessed by means of a power spectral analysis of heart rate variability. Four single nucleotide polymorphisms (SNPs) in ABCB1 (rs1045642, rs1128503, rs2032582, and rs2235048) were genotyped using the TaqMan method. RESULTS: For aripiprazole, sympathetic and total autonomic nervous activities were significantly lower in the rs1045642 T allele carrier-rs2235048 C allele carrier group than in the rs1045642 non-T allele carrier-rs2235048 non-C allele carrier group. In addition, in the aripiprazole group, the T-C-T-A haplotype (rs1045642-rs2235048-rs1128503-rs2032582) was associated with decreased ANS activity. However, there were no significant associations between ANS activity and ABCB1 gene polymorphisms in the risperidone, olanzapine, and quetiapine groups. Multiple regression analysis revealed that sympathetic and total nervous activities were significantly associated with the ABCB1 rs1045642-rs2235048 genotype and the T-C-T-A haplotype (rs1045642-rs2235048-rs1128503-rs2032582). CONCLUSION: We suggest that ABCB1 genetic polymorphisms affect aripiprazole-related ANS dysfunction but do not affect risperidone-, olanzapine-, or quetiapine-related ANS dysfunction.

Nonalcoholic Fatty Liver Disease in University Rugby Football Players.

Physical activity improves various metabolic disturbances. The effect of physical activity on non-alcoholic fatty liver disease (NAFLD) has not been defined, particularly in athletes who are able to consume a diet to increase body mass. The aim of this study was to evaluate the prevalence of NAFLD and associated factors of NAFLD among male university rugby football players [n = 69, 37 forwards (FW) and 32 backs (BK)], relative to age-matched controls (CON; n = 29). For FW players exercise consists of physical contact play, such as ruck, mall, scrum, and tackle. For BK players exercise consists of sprints and endurance running. Liver function tests and bioimpedance analysis to assess body composition were performed. Subjects consuming ≤ 20 g/day of ethanol and exhibiting an aspartate transaminase (AST) level ≥ 33 U/L, and/or alanine transaminase (ALT) level ≥ 43 U/L, were considered to have NAFLD. The PNPLA3 and MTP genotypes were determined using real-time polymerase chain reaction (PCR). The body mass index, body fat mass, and lean body mass were significantly higher in the FW group than in the BK and CON groups (P < 0.05). The total cholesterol, low-density lipoprotein cholesterol, triglyceride, AST, ALT, and alkaline phosphatase levels were significantly higher in the FW group than in the CON group (P < 0.05). The prevalence of NAFLD was significantly higher in the FW group than in the BK group and CON group (18.9, 8.6, and 0.0%, respectively), whereas there were non-significant between-group differences in the frequency of the PNPLA3 and MTP genotypes. These findings indicate that rugby football players, especially those in the FW position, are at higher risk of developing NAFLD, which emphasizes the role of diet and exercise in the development of NAFLD.

Increasing levels of daily physical activity for arterial stiffness reduction in older women: a community-based pilot study.

BACKGROUND: The recent Japanese official physical activity (PA) guidelines for health promotion recommend increasing PA by 10 minutes per day (Plus 10), which generally corresponds to about 1000 steps per day. However, whether habitually increasing PA in daily life improves arterial stiffness in older people is unclear. The present study aimed to examine the effects of habitually increasing PA during an intervention on arterial stiffness in older women. METHODS: Twenty-one older women (age, 76±1 years) participated in supervised group activity and seated exercise for 60 min per session, once each week during an 8-week intervention. The women wore an activity monitor for 1 week to determine baseline values and for the 8 weeks of intervention. Arterial stiffness was assessed before and after the intervention using the Cardio-Ankle Vascular Index (CAVI). RESULTS: Based on changes in steps between baseline and the intervention, the participants were assigned to control (<1000 steps/day, N.=14) or PA-increased (≥1000 steps/day, N.=7) groups with changes of -138±198 steps/day and 2,047±580 steps/day, respectively. The CAVI was significantly reduced only in the PA-increased group (Pre, 9.2±0.2; Post, 9.0±0.2 units), and changes in CAVI were significantly inversely correlated with changes in step counts (rs=-0.62). CONCLUSIONS: Habitually increasing PA in daily life during 8-week intervention can induce a small but significant reduction in arterial stiffness among older women.

Effects of four atypical antipsychotics on autonomic nervous system activity in schizophrenia.

Antipsychotic drugs are associated with autonomic nervous system (ANS) dysfunction in patients with schizophrenia, but the effects of individual atypical antipsychotic drugs are not clear. This study investigated how four atypical antipsychotic drugs-risperidone, olanzapine, aripiprazole, and quetiapine-differ in their effects on ANS activity. A total of 241 Japanese patients with schizophrenia participated in this study. All of the participants received an atypical antipsychotic as monotherapy: 90 participants received risperidone, 68 olanzapine, 52 aripiprazole, and 31 quetiapine. ANS activity was assessed by means of a power spectral analysis of heart rate variability. The quetiapine group showed significantly diminished sympathetic and parasympathetic activity compared with the risperidone and aripiprazole groups and significantly lower sympathetic activity relative to olanzapine. In addition, multiple regression analysis showed that the type of antipsychotic drug significantly influenced ANS activity. We suggest that, among the antipsychotics examined-risperidone, olanzapine, aripiprazole and quetiapine-quetiapine has the strongest effect on ANS activity.

Prevalence of Frailty Assessed by Fried and Kihon Checklist Indexes in a Prospective Cohort Study: Design and Demographics of the Kyoto-Kameoka Longitudinal Study.

OBJECTIVE: The Kyoto-Kameoka Study was launched in 2011-2012 to identify the associations among food intake, nutritional status, physical activity, oral function, quality of life or social capital, the use of long-term care insurance (LTCI) system, and healthy lifespan in community-dwelling older people as a part of the World Health Organization Safe Community program. DESIGN: A prospective cohort study, reporting baseline demographics (cross-sectional data). SETTING AND PARTICIPANTS: We conducted 2 mailed self-administered questionnaire surveys; one is a complete population survey with a comprehensive survey of needs in the sphere of daily life (NSDL) that included 2 different frailty indexes, the Kihon Checklist (KCL) and the Fried phenotype, socioeconomic status, general and psychological health, and social relationships; followed by the more detailed Health and Nutrition Survey. A slightly modified NSDL survey was conducted again in 2013. Survival time, LTCI certification, and medical and long-term care costs after the baseline survey will be followed. RESULTS: Of 18,231 NSDL questionnaires distributed, 13,294 people responded (response rate: 72.92%; mean age 73.7 ± 6.4 and 75.1 ± 7.2 years for men and women, respectively; 12,054 people without and 1240 with LTCI certification). In people without LTCI, the proportion of robust, prefrail, and frail were 30.3%, 59.8%, and 9.9% in men and 25.3%, 64.7%, and 10.0% in women, according to the Fried index. The proportion of frail people as defined by KCL ≥7 was 30.8% in men and 33.3% in women. CONCLUSIONS: The study is the first to document frailty prevalence using both Fried and KCL measures with a complete city population survey among older Japanese in the community as a part of World Health Organization Safe Community program. The study is expected to provide valuable evidence of the effects of lifestyle habits on long-term care prevention and healthy life span.

Long term effects of smoking cessation in hospitalized schizophrenia patients.

BACKGROUND: The prevalence of smoking in patients with schizophrenia is higher than that in the general population and is an important medical issue. Short-term smoking cessation tends to worsen psychiatric symptoms in patients with schizophrenia but decreases sympathetic nervous system activity and improves plasma cholesterol levels in healthy people. Few studies have assessed the long-term effects of smoking cessation in patients with schizophrenia. METHODS: Subjects were 70 Japanese patients with schizophrenia (38 smokers, 32 non-smokers). We compared the following clinical parameters between the two groups at baseline (before smoking cessation) and in each group separately between baseline and at three years after smoking cessation: autonomic nervous system activity, plasma cholesterol levels, body weight, drug therapy, and Global Assessment of Functioning scores. We also compared the mean changes in clinical parameters throughout this study between the groups at both time points. Autonomic nervous system activity was assessed by power spectral analysis of heart rate variability. RESULTS: Parasympathetic nervous system activity and the doses of antiparkinsonian drugs in smokers were significantly higher than those in non-smokers at baseline. Smoking cessation was associated with significantly decreased sympathetic nervous system activity and decreased doses of antipsychotics and antiparkinsonian drugs at three years after smoking cessation. However, there was no significant difference in the mean change in clinical factors scores, except for Global Assessment of Functioning scores, between smokers and non-smokers at three years after smoking cessation. CONCLUSIONS: Our results suggest that smoking reduces both autonomic nervous system activity and the effectiveness of drug therapy with antipsychotics and antiparkinsonian drugs in patients with schizophrenia, but that both factors could be ameliorated over the long term by smoking cessation. Taken together with the findings of previous studies, smoking cessation in patients with schizophrenia has many long-term positive physiological effects.

Association of the Cholinergic Muscarinic M2 Receptor with Autonomic Nervous System Activity in Patients with Schizophrenia on High-Dose Antipsychotics.

BACKGROUND: Patients with schizophrenia have abnormal autonomic nervous system (ANS) activity compared with the general population. One reason for this difference is the muscarinic affinity for antipsychotic drugs; therefore, single nucleotide polymorphisms (SNPs) of the muscarinic receptor gene influence this ANS dysfunction. This study sought to determine the effect of SNPs of the cholinergic muscarinic receptor (CHRM) gene on ANS activity in patients with schizophrenia receiving antipsychotic drugs. METHODS: A total of 173 Japanese patients with schizophrenia were included in this study. Heart rate variability (HRV) was measured as an index of ANS activity. SNPs in CHRM1 (rs542269 and rs2075748), CHRM2 (rs324640, rs8191992, rs1824024, and rs7810473), and CHRM3 (rs3738435, rs4620530, and rs6429157) were genotyped using the TaqMan® method. Patients were grouped according to standard equivalent conversions of chlorpromazine (CP) into a high-CP group (HG; ≥1,000 mg) and a low-CP group (LG; <1,000 mg). ANS activity was compared between the groups. In addition, we compared the total, low-frequency (LF), high-frequency (HF), and LF/HF components of the patients' HRV, and the genotype of the SNPs in both the HG and LG groups. Bonferroni correction was applied for multiple comparisons, and the Bonferroni-corrected critical p value was <0.005. RESULTS: The A allele of the CHRM2 rs8191992 polymorphism in HG was associated with decreased ANS activity. CONCLUSION: Our results show reduced ANS activity in association with the CHRM2 rs8191992 polymorphism in patients with schizophrenia on high-dose antipsychotics. CHRM2 polymorphisms may play an important role in ANS activity in patients with schizophrenia.