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.

Pharmacological Treatment of Schizophrenia: Japanese Expert Consensus.

INTRODUCTION: Conventional treatment guidelines of schizophrenia do not necessarily provide solutions on clinically important issues. METHODS: A total of 141 certified psychiatrists of the Japanese Society of Clinical Neuropsychopharmacology evaluated treatment options regarding 19 clinically relevant situations in the treatment of schizophrenia with a 9-point scale (1="disagree" and 9="agree"). RESULTS: First-line antipsychotics varied depending on predominant symptoms: risperidone (mean±standard deviation score, 7.9±1.4), olanzapine (7.5±1.6), and aripiprazole (6.9±1.9) were more likely selected for positive symptoms; aripiprazole (7.6±1.6) for negative symptoms; aripiprazole (7.3±1.9), olanzapine (7.2±1.9), and quetiapine (6.9±1.9) for depression and anxiety; and olanzapine (7.9±1.5) and risperidone (7.5±1.5) for excitement and aggression. While only aripiprazole was categorized as a first-line treatment for relapse prevention (7.6±1.0) in patients without noticeable symptoms, aripiprazole (8.0±1.6) and brexpiprazole (6.9±2.3) were categorized as such for social integration. First-line treatments in patients who are vulnerable to extrapyramidal symptoms include quetiapine (7.5±2.0) and aripiprazole (6.9±2.1). DISCUSSION: These clinical recommendations represent the expert consensus on the use of a particular antipsychotic medication for a particular situation, filling a current gap in the literature.

Pharmacological management of bipolar disorder: Japanese expert consensus.

OBJECTIVES: The aim of this study was to develop a consensus guideline by certified experts of the Japanese Society of Clinical Neuropsychopharmacology on the psychopharmacological treatment for bipolar disorders I and II (BP-I and BP-II), in order to fill the gap in the literature and provide more concrete guidance for challenging and controversial real-world situations. METHODS: Experts were asked to assess treatment options regarding 19 clinical situations of bipolar disorder with a nine-point Likert scale (one = "disagree" and nine = "agree"). According to the responses from 119 experts, the options were categorized into the first-, second-, and third-line treatments. RESULTS: For the treatment of BP-I, lithium monotherapy was categorized as a first-line treatment for manic episodes (mean ± standard deviation score, 7.0 ± 2.2), depressive episodes (7.1 ± 2.0), and the maintenance phase (7.8 ± 1.8). Combination therapy of lithium and an atypical antipsychotic was endorsed for manic episodes (7.7 ± 1.7), depressive episodes with (7.1 ± 2.0) and without mixed features (6.9 ± 2.2), and the maintenance phase (6.9 ± 2.1). Similarly, in BP-II, lithium monotherapy was categorized as a first-line treatment for hypomanic episodes (7.3 ± 2.2), depressive episodes (7.0 ± 2.2), and the maintenance phase (7.3 ± 2.3), while combination therapy of lithium and an atypical antipsychotic was recommended for hypomanic episodes (6.9 ± 2.4).No antipsychotic monotherapy or antidepressant treatment was categorized as a first-line treatment for any type of episode. CONCLUSIONS: These recommendations reflect the current evidence and represent the experts' consensus on using lithium for the treatment of bipolar disorder. Clinicians should consider the effectiveness and adverse effects of antipsychotic and antidepressant medications for the treatment of bipolar disorder.

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.

Pharmacological management of depression: Japanese expert consensus.

BACKGROUND: Clinically relevant issues in the real-world treatment of depression have not always been captured by conventional treatment guidelines. METHODS: Certified psychiatrists of the Japanese Society of Clinical Neuropsychopharmacology were asked to evaluate treatment options regarding 23 clinical situations in the treatment of depression using a 9-point Likert scale (1="disagree" and 9="agree"). According to the responses of 114 experts, the options were categorized into first-, second-, and third-line treatments. RESULTS: First-line antidepressants varied depending on predominant symptoms: escitalopram (mean ± standard deviation score, 7.8 ± 1.7) and sertraline (7.3 ± 1.7) were likely selected for anxiety; duloxetine (7.6 ± 1.9) and venlafaxine (7.2 ± 2.1) for loss of interest; mirtazapine for insomnia (8.2 ± 1.6), loss of appetite (7.9 ± 1.9), agitation and severe irritation (7.4 ± 2.0), and suicidal ideation (7.5 ± 1.9). While first-line treatment was switched to either an SNRI (7.7 ± 1.9) or mirtazapine (7.4 ± 2.0) in the case of non-response to an SSRI, switching to mirtazapine (7.1 ± 2.2) was recommended in the case of non-response to an SNRI, and vice versa (switching to an SNRI (7.0 ± 2.0) in the case of non-response to mirtazapine). Augmentation with aripiprazole was considered the first-line treatment for partial response to an SSRI (7.1 ± 2.3) or SNRI (7.0 ± 2.5). LIMITATIONS: The evidence level of expert consensus is considered low. All included experts were Japanese. CONCLUSIONS: Recommendations made by experts in the field are useful and can supplement guidelines and informed decision making in real-world clinical practice. We suggest that pharmacological strategies for depression be flexible and that each patient's situational needs as well as the pharmacotherapeutic profile of medications be considered.

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.

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.

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.

Effects of NRG1 genotypes on orbitofrontal sulcogyral patterns in Japanese patients diagnosed with schizophrenia.

AIM: Numerous reports have described differences in the distribution of orbitofrontal cortex (OFC) sulcogyral patterns between patients with schizophrenia (SZ patients) and healthy controls (HC). Alterations in OFC morphology are also observed in those at high risk for developing SZ and in first-episode SZ, suggesting that genetic associations may be extant in determining OFC sulcogyral patterns. We investigated the association between single nucleotide polymorphisms (SNP) in NRG1 and OFC sulcogyral patterns. METHODS: A total of 59 Japanese patients diagnosed with SZ and 60 HC were scanned on a 1.5-T magnet. Patients were also assessed clinically. OFC sulcogyral patterns were evaluated for each participant, and genotyping was performed for four SNP in NRG1 (SNP8NRG243177, SNP8NRG221533, SNP8NRG241930, and rs1081062). RESULTS: There were significant differences in the distribution of OFC sulcogyral patterns between SZ patients and HC (χ(2) = 6.52, P = 0.038). SZ patients showed an increase in the frequency of Type III expression, which was associated with an earlier age of disease onset (ß = -0.302, F = 4.948, P = 0.030). Although no difference was found in genotype frequencies between SZ patients and HC, an NRG1 SNP, SNP8NRG243177, was associated with Type II expression in SZ patients (ß = 0.237, F = 4.120, P = 0.047). CONCLUSION: Our results suggest that OFC sulcogyral pattern formation in schizophrenia may be associated with NRG1 allele frequency, which is closely related to neurodevelopment.

Dose-dependent effect of antipsychotic drugs on autonomic nervous system activity in schizophrenia.

BACKGROUND: Antipsychotic drugs are considered a trigger factor for autonomic dysregulation, which has been shown to predict potentially fatal arrhythmias in schizophrenia. However, the dose-dependent effect of antipsychotic drugs and other psychotropic drugs on autonomic nervous system (ANS) activity remain unclear. The purpose of this study was to investigate the dose-dependent effect of antipsychotic drugs and other clinical factors on ANS activity in an adequate sample size of patients with schizophrenia. METHODS: A total of 211 Japanese patients with schizophrenia and 44 healthy subjects participated in this study. ANS activity was assessed by means of heart rate variability (HRV) power spectral analysis. Antipsychotic drug treatment and various clinical factors were investigated for each participant. The patient group was categorized into three subgroups according to daily dose of antipsychotic drug, and HRV was compared between groups. RESULTS: The results showed significantly decreased low-frequency and high-frequency components of HRV in the patient group compared to the control group. The high-dose group showed a significantly lower HRV than the medium-dose group and an even lower HRV than the low-dose group. In addition, a significant association between HRV and antipsychotic drug dose was identified by multiple regression analysis. HRV was not associated with age, sex, body mass index, duration of illness, or daily dose of other psychotropic drugs. CONCLUSION: These results suggest that antipsychotic drugs exert a significant dose-dependent effect on the extent of decline in ANS activity, and that optimal antipsychotic medication is required to avoid possible cardiovascular adverse events in patients with schizophrenia.

Comparison of prevalence of metabolic syndrome in hospital and community-based Japanese patients with schizophrenia.

BACKGROUND: Lifestyle factors, such as an unbalanced diet and lack of physical activity, may affect the prevalence of metabolic syndrome (MetS) in schizophrenic patients. The aim of this study was to compare the MetS prevalence between inpatients and outpatients among schizophrenic population in Japan. METHODS: We recruited inpatients (n = 759) and outpatients (n = 427) with a Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) diagnosis of schizophrenia or schizoaffective disorder from 7 psychiatric hospitals using a cross-sectional design. MetS prevalence was assessed using three different definitions, including the adapted National Cholesterol Education Program Adult Treatment Panel (ATP III-A). RESULTS: The overall MetS prevalences based on the ATP III-A definition were 15.8% in inpatients and 48.1% in outpatients. In a logistic regression model with age and body mass index as covariates, being a schizophrenic outpatient, compared to being a schizophrenic inpatient, was a significant independent factor (odds ratio = 3.66 for males, 2.48 for females) in the development of MetS under the ATP III-A definition. The difference in MetS prevalence between inpatients and outpatients was observed for all age groups in males and for females over 40 years of age. CONCLUSIONS: Outpatients with schizophrenia or schizoaffective disorder in Japan had a high prevalence of MetS compared to inpatients. MetS in schizophrenic outpatients should be carefully monitored to minimize the risks. A change of lifestyle might improve MetS in schizophrenic patients.

Prevalence of metabolic syndrome among patients with schizophrenia in Japan.

AIMS: In an Asian population, the criteria for metabolic syndrome (MetS) are different from those for Western populations. The aim of this study was to assess the MetS prevalence among patients with schizophrenia or schizoaffective disorder in Japan. METHODS: We recruited patients (n=1186), aged 54.8±14.8 (mean±SD) years old with the DSM-IV diagnosis of schizophrenia or schizoaffective disorder who were admitted to seven psychiatric hospitals using a cross-sectional design. MetS prevalence was assessed by three different definitions, including the adapted National Cholesterol Education Program Adult Treatment Panel (ATP III-A). Comparative analysis was performed with schizophrenic subjects and 886 participants from the Iwaki Health Promotion Project 2008 as representative of general population. RESULTS: The overall MetS prevalence based on the ATP III-A definition was 27.5%, with 29.8% in male and 25.3% in female patients. In a logistic regression model with age and body mass index as covariates, being schizophrenic was a significant independent factor (odds ratio=2.00 for males, 2.13 for females) in the development of MetS under the ATP III-A definition. The difference of MetS prevalence between patients and the general population was observed for those under 60 years of age. CONCLUSIONS: Patients with schizophrenia or schizoaffective disorder in Japan had high prevalence of MetS compared to the general population, and was most apparent for those under 60 years of age. The MetS in schizophrenic patients should be carefully monitored to minimize the risks.

Autonomic nervous system activity and psychiatric severity in schizophrenia.

AIMS: Schizophrenia patients have a mortality rate two to three-fold higher than that of the general population. Despite the disorder's widespread recognition, how and to what extent autonomic nervous system (ANS) activity contributes to schizophrenia remains inconclusive. The aim of the present study, therefore, was to determine the extent of ANS activity depression with respect to healthy, well-matched control subjects and the severity of psychiatric disorders as determined using the Global Assessment of Functioning (GAF) scale among schizophrenia patients with special reference to antipsychotic dose. METHODS: This study included 71 schizophrenia patients and 72 healthy controls. ANS activity was assessed by means of heart rate variability power spectral analysis. RESULTS: ANS-related spectral parameters were three-four-fold lower in the patients compared to the control group (P < 0.01). Furthermore, when the patients without cardiovascular complications were classified according to GAF score, overall ANS (P = 0.033) and parasympathetic nervous system (PNS) activity (P = 0.025) were significantly reduced in the low-GAF as compared to the high-GAF group. Partial correlation analyses demonstrated that ANS activity was significantly correlated with GAF score while statistically eliminating the effects of age, gender, body mass index, antipsychotic dose, and lipid profiles of the patient population. CONCLUSION: The significantly lower ANS activity in the low-GAF group suggests that such autonomic functional depression could be associated with the severity of schizophrenia. The present data further imply that schizophrenia patients with more depressed overall ANS and PNS activity might encounter increasing risks for cardiovascular events such as sudden death.

Dopamine D2 receptor gene polymorphisms are associated with suicide attempt in the Japanese population.

BACKGROUND: Some reports have suggested the involvement of the D2 dopaminergic function in the expression of suicidal behavior. Here, we examined associations between suicide attempts and two kinds of functional polymorphisms in the dopamine D2 receptor (DRD2) gene, namely, TaqIA and -141C Ins/Del. METHODS: Subjects included 120 suicide attempters and 123 unrelated volunteers. Those who attempted suicide were severely injured and were transferred to the emergency unit in our university hospital. To determine each genotype, we performed polymerase chain reaction and restriction fragment length polymorphism analyses. RESULTS: We found significant differences in genotypic and allelic frequencies of -141C Ins/Del and TaqIA polymorphisms between suicide attempters and healthy controls (-141C Ins/Del, p = 0.01; TaqIA,p = 0.036). The Ins allele of -141C Ins/Del was significantly more frequent in suicide attempters (p = 0.011), as well as the A2 allele of TaqIA (p = 0.017). Haplotype analysis revealed no significant linkage disequilibrium between -141C Ins/Del and TaqIA polymorphisms (D' = 0.226, r(2) = 0.016, p = 0.10). CONCLUSIONS: These findings suggest that DRD2 gene polymorphisms may be involved in the biological susceptibility to suicide.