Heart Rate Variability with Deep Breathing in Drug-Naïve Patients with Schizophrenia.

Abnormal autonomic nervous system (ANS) function may result in poor outcomes in patients with schizophrenia. Altered cardio-respiratory coupling, which indicates suppression of vagal activity, was identified as an important trait in patients with schizophrenia and their unaffected relatives. Heart rate variability (HRV) in standardized bedside reflex tests has been studied, mostly in medicated patients with schizophrenia whose ANS function could be influenced by medication. Our study aimed to explore the autonomic function differences between drug-naïve patients with schizophrenia and healthy individuals during challenge tests combining respiration and HRV analysis. Forty-two drug-naïve patients with schizophrenia were matched with 42 healthy controls in terms of age and gender. Their beat-to-beat blood pressure and heart rate were monitored in the supine position as a survey of ANS function, and the mean heart rate range (MHRR) was measured under deep-breathing challenge. A decreased MHRR, a sensitive sign indicating an impaired parasympathetic response, during the deep-breathing challenge among the drug-naïve patients with schizophrenia was found. Drug-naïve patients with schizophrenia may have a parasympathetic dysfunction in the early stages of schizophrenia before medication is introduced, which could be considered a neurobiological marker in the pathophysiology of schizophrenia.

The Association between the Level of Plasma Oxytocin and Craving among Former Heroin Users.

BACKGROUND: Animal studies have demonstrated that oxytocin can influence addiction behaviors and might interact with the dopaminergic system, which is a key component of addiction behaviors. However, related evidence from clinical studies is scarce. The aim of our study was to explore the relationship between plasma oxytocin level and heroin craving among patients receiving methadone maintenance treatment, and to ascertain whether this relationship is moderated by novelty-seeking. METHODS: The study was conducted in a methadone maintenance therapy clinic of a medical center in Taiwan. Seventy-seven patients with heroin addiction were enrolled. Plasma oxytocin was measured using an ELISA kit. Craving was assessed using an established instrument, the Chinese Craving Scale. RESULTS: A significant negative association was found between the plasma oxytocin level and craving score, which remained robust after controlling the effects of social support and low-density lipoprotein cholesterol. An interaction between oxytocin and novelty-seeking indicated that this relationship was stronger among patients with a lower level of novelty-seeking. CONCLUSION: This finding may be taken into account in future studies and may provide a basis for the development of potential treatment for addiction. The effect of oxytocin for the treatment of opioid dependence might be modulated by some psychological factors.

Association between Blood Level of Plasma Oxytocin and Novelty Seeking among Methadone-Maintained Heroin Users.

BACKGROUND: Oxytocin interacts with the dopaminergic system, which plays a role in addiction behaviors. The association between oxytocin and addiction was confirmed in animal studies. Novelty seeking is one of the predictors and indicators of drug addiction. The aim of the present study was to probe the association between oxytocin and novelty seeking. METHODS: The study was conducted in a methadone maintenance therapy clinic of a medical center in Taiwan; 77 patients with heroin dependency were enrolled. Plasma oxytocin was measured using an ELISA kit. Novelty seeking was measured using an established instrument (the novelty seeking subscale of the Tridimensional Personality Questionnaire). RESULTS: A significant negative association (ρ = -0.27, p = 0.02; r = -0.34, p = 0.003) between the blood level of plasma oxytocin and novelty seeking was found. This association was significant after controlling the effects of perceived social support and the dosage of methadone (r = -0.32, p = 0.006). CONCLUSION: The negative association between oxytocin and novelty seeking may provide insight into future treatments for addiction. © 2015 S. Karger AG, Basel.

Improving learning performance with happiness by interactive scenarios.

Recently, digital learning has attracted a lot of researchers to improve the problems of learning carelessness, low learning ability, lack of concentration, and difficulties in comprehending the logic of math. In this study, a digital learning system based on Kinect somatosensory system is proposed to make children and teenagers happily learn in the course of the games and improve the learning performance. We propose two interactive geometry and puzzle games. The proposed somatosensory games can make learners feel curious and raise their motivation to find solutions for boring problems via abundant physical expressions and interactive operations. The players are asked to select particular operation by gestures and physical expressions within a certain time. By doing so, the learners can feel the fun of game playing and train their logic ability before they are aware. Experimental results demonstrate that the proposed somatosensory system can effectively improve the students' learning performance.

Effects of C825T polymorphism of the GNB3 gene on availability of dopamine transporter in healthy volunteers--a SPECT study.

Striatal dopaminergic activity is significantly correlated with various cognitive activities, mood regulation, and even metabolic homeostasis, and is modulated by the dopamine transporter (DAT). The availability of DAT could be regulated by presynaptic autoreceptors, which are G-protein coupled receptors; however, whether functional variations in the common downstream signaling molecule, G-protein, could cause individual differences in presynaptic transporter availability remains unclear. To investigate this relationship, the DAT availability in seventy-eight healthy subjects was approximated using single photon emission computed tomography (SPECT) with [(99m)Tc] TRODAT-1, a radio-labeled form of tropan derivative for the selective labeling of DAT. The C825T single nucleotide polymorphism (SNP) (rs5443) of the beta subunit of the G-protein second messenger (GNß3) gene was genotyped, and analysis of variance showed a significant difference in striatal DAT when referenced to the entire occipital lobe among the three genotypes. Post hoc independent t tests were also performed, and showed that the striatal DAT availability of the CC genotype was higher than that of the other two genotypes. These results indicated that genetic variation in the common downstream signaling molecule of the dopamine autoreceptor could affect the functional status of the striatal dopamine system. These results together with the known role of the GNß3 gene might provide further evidence to support the common effect of the striatal dopamine system on mood and metabolic regulation.

Positive Symptoms in Antipsychotic-naïve Schizophrenia are Associated with Increased Body Mass Index after Treatment.

OBJECTIVE: Weight gain is an important risk factor for morbidity and mortality among patients with schizophrenia. We speculated that positive symptoms, related to dopaminergic hyperactivity and altered mesolimbic function, are associated with weight gain. METHODS: Twenty-two antipsychotic-naïve, first-episode patients with schizophrenia were enrolled. The Positive and Negative Syndrome Scale was completed at enrollment and follow-up. Body mass index (BMI) was also measured. RESULTS: The increase in BMI, after 6.04 ± 2.16 years of follow-up, was associated with positive symptoms, but not negative symptoms, before treatment with antipsychotics in antipsychotic-naïve patients with schizophrenia. CONCLUSION: This finding implied that dopaminergic hyperactivity could be an important factor to predict the treatment outcome. Body weight control is important for the health management of patients with schizophrenia with more severe positive symptoms.

C825T polymorphism of the GNB3 gene on valproate-related metabolic abnormalities in bipolar disorder patients.

BACKGROUND: Valproate (VPA) is a mood stabilizer for treating patients with bipolar disorder (BD). It may cause metabolic abnormalities in certain bipolar patients. However, the genetic factors that influence the susceptibility remain unclear. Genetic polymorphism of the G-protein ß3 subunit (GNB3) is reported to be associated with metabolic phenotypes. In the current study, we investigated the possible associations between the GNB3 variation and VPA-induced metabolic abnormalities. METHODS: Subjects (n = 96) who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for BD were recruited from the National Cheng Kung University Hospital. Their metabolic indices were measured. RESULTS: The variation of GNB3 C825T showed an association with higher plasma total cholesterol (P = 0.037), triglyceride (P = 0.014), and leptin (P < 0.001) levels in BD patients treated with VPA. After adjusting for age, sex, types of BDs, and serum concentration of VPA, the variation of GNB3 C825T remained significantly associated with the levels of serum leptin and body mass index (BMI; P < 0.001 and P = 0.030, respectively). In addition, the GNB3 C825T showed significant drug-single-nucleotide polymorphism interactions with insulin levels (P = 0.033), triglyceride levels (P = 0.013), leptin levels (P = 0.013), and BMI (P = 0.018). These results indicated that the T allele may be associated with lower serum leptin levels and BMI in BD patients treated with VPA. CONCLUSIONS: The current study provides evidence that BD patients who are T allele carriers of the GNB3 C825T polymorphism have a lower risk for VPA-induced metabolic abnormalities. Further studies about the underlying mechanisms of G protein in VPA-induced metabolic abnormalities are warranted.

The association between plasma cholesterol and the effect of tryptophan depletion on heart rate variability.

Studies on the cholesterol-serotonin hypothesis and its link to mood disorders are scarce. In addition, little is known about the association between cholesterol and the effects of tryptophan depletion (TD). The aim of the present study was to investigate the association between plasma cholesterol and changes in heart rate variability (HRV), an important marker of depression and anxiety, after TD. The plasma cholesterol levels of 28 healthy participants were noted, and their HRVs were measured by spectrum analysis. TD was carried out on testing day, and participants provided blood samples just before and 5 hours for tryptophan level after TD. HRV was measured again after TD. An association was found between plasma cholesterol levels and the change in HRV. Decreased high frequency HRV was marginally associated with lower levels of high-density lipoprotein cholesterol, while increased low frequency HRV was significantly associated with lower levels of total and low-density lipoprotein cholesterol. Our findings indicate that low cholesterol levels may play parts of role in the mechanism of the deactivation of parasympathetic, and activation of sympathetic, functions induced by altered serotonergic function.

Higher mortality and years of potential life lost of suicide in patients with schizophrenia.

Patients with schizophrenia could have a higher risk of mortality. We compared the risk of mortality and the years of potential life lost (YPLL) associated with various causes of death between patients with schizophrenia and the general population. A total of 4,298 patients with schizophrenia were included. The cohort was linked to the Taiwan Death Register between 1998 and 2010 using personal identification numbers, which showed 367 patients with schizophrenia had died by the end of 2010. The standard mortality ratios (SMRs) and YPLL were analyzed by age, sex and cause of death. The overall SMR was significantly higher in patients with schizophrenia. Suicide had the most significantly greater SMR, and the SMRs for physical illnesses, accidents and injuries were all significantly greater in patients with schizophrenia. Suicide had the largest YPLL/deaths among all causes of mortality in patients with schizophrenia. Suicide had the most significantly greater risk of mortality among patients with schizophrenia as compared with the general population. Patients with schizophrenia are highly vulnerable in terms of increased mortality and require special attention.

Increased Readmission Risk and Healthcare Cost for Delirium Patients without Immediate Hospitalization in the Emergency Department.

OBJECTIVE: Hospitalization of patients with delirium after visiting the emergency department (ED) is often required. However, the readmission risk after discharge from the ED should also be considered. This study aimed to explore whether (i) immediate hospitalization influences the readmission risk of patients with delirium; (ii) the readmission risk is affected by various risk factors; and (iii) the healthcare cost differs between groups within 28 days of the first ED visit. METHODS: Using the National Health Insurance Research Database, the data of 2,780 subjects presenting with delirium at an ED visit from 2000 to 2008 were examined. The readmission risks of the groups of patients (i.e., patients who were and were not admitted within 24 hours of an ED visit) within 28 days were compared, and the effects of the severities of different comorbidities (using Charlson's comorbidity index, CCI), age, gender, diagnosis and differences in medical healthcare cost were analyzed. RESULTS: Patients without immediate hospitalization had a higher risk of readmission within 3, 7, 14, or 28 days of discharge from the ED, especially subjects with more severe comorbidities (CCI≥3) or older patients (≥65 years). Subjects with more severe comorbidities or older subjects who were not admitted immediately also incurred a greater healthcare cost for re-hospitalization within the 28-day follow-up period. CONCLUSION: Patients with delirium with a higher CCI or of a greater age should be carefully considered for immediate hospitalization from ED for further examination in order to reduce the risk of re-hospitalization and cost of healthcare.

Factors related to metabolic parameters in medicated patients with major depressive disorder--a naturalistic study.

The aim of this study was to examine the metabolic parameters, including body mass index (BMI), homeostasis model assessment-estimated insulin resistance (HOMA-IR), homeostasis model assessment-estimated pancreatic ß-cell function (HOMA-ß), and lipid plasma level, in medicated patients with major depressive disorder (MDD) and to assess factors related to metabolic parameters in patients with MDD. 121 patients with MDD and 63 controls were recruited. The Hamilton Depression Rating Scale (HDRS), Wisconsin Card Sorting Test (WCST), Continuous Performance Test (CPT), and Finger-Tapping Test (FTT), were administered. BMI, HOMA-IR, and HOMA-ß were calculated as modifiable metabolic parameters. The FTT results and BMI in depressed patients were significantly poorer and lower, respectively, than those of the controls. However, no significant differences were noted between MDD patients and controls included metabolic parameters and other neuropsychological tests. Among depressed patients, higher BMI is significantly related with lower education, no tobacco use, and male. The result demonstrated metabolic parameters could be neutral among medicated patients with MDD, particularly in non-elderly Asian individuals. The deficits of psychomotor speed could be more prominent than other cognitive alterations in patient with MDD.

Plasma oxytocin levels in major depressive and bipolar II disorders.

Oxytocin may play a role in mood regulation. Research has shown the plasma oxytocin level of patients with bipolar I disorder (BD I) during a manic episode was significantly higher than that of BD I patients of other statuses, and also that of healthy subjects. However, whether or not a difference in the level of oxytocin exists between patients with major depressive disorder (MDD) and those with BD II is unclear. This study aimed to investigate the plasma oxytocin levels in MDD and BD II patients in a depressive episode. 119 healthy controls, 135 BD II patients, and 97 MDD patients were enrolled. All of the BD II and MDD patients were drug-naïve, with baseline depressive status 17-item Hamilton Depression Rating Scale scores >15. The plasma oxytocin level of the BD II patients was significantly higher than that of the MDD patients and controls at baseline. After treatment, the plasma oxytocin level of the BD II patients increased significantly; however, in the MDD group, the oxytocin level decreased slightly after treatment. Our findings suggested more significant plasma oxytocin dysregulation in the patients in the BD II group than in the MDD patients and controls, both before and after treatment.

The correlation between perceived social support, cortisol and brain derived neurotrophic factor levels in healthy women.

In this study, the role of brain derived neurotrophic factor (BDNF) in stress resilience was investigated. With a focus on healthy subjects, we explored whether plasma BDNF levels are correlated with the dexamethasone suppression test (DST) and subjectively perceived social support status. Moreover, we examined the possible interacting effect of DST status and perceived social support on BDNF levels. Seventy-two healthy volunteers, 44 females and 28 males, were recruited from the community and completed the perceived routine support subscale of Measurement of Support Function (PRS_MSF) questionnaire. Plasma BDNF levels and DST suppression rate with the low dose DST were measured. There was a significant positive correlation between BDNF and DST suppression rate in the female subjects. This was also true for the plasma BDNF levels and PRS_MSF in the female subjects. The positive correlation between BDNF and PRS_MSF was significant only in female subjects with low DST suppression rates. Plasma BDNF levels were associated with stress resilience in a sex-specific manner. Subjects' belief in social support might buffer the biological stress reactions. Differences in social perception and the biological stress response between men and women merits further investigation.

The Association between Baseline Subjective Anxiety Rating and Changes in Cardiac Autonomic Nervous Activity in Response to Tryptophan Depletion in Healthy Volunteers.

The aim of this study was to investigate the influence of serotonin on anxiety and autonomic nervous system (ANS) function; the correlation between subjective anxiety rating and changes of ANS function following tryptophan depletion (TD) in healthy volunteers was examined. Twenty-eight healthy participants, consisting of 15 females and 13 males, with an average age of 33.3 years, were recruited.Baseline Chinese Symptom Checklist-90-Revised and ANS function measurements were taken. TD was carried out on the testing day, and participants provided blood samples right before and 5 hours after TD. ANS function, somatic symptoms, and Visual Analogue Scales (VASs) were determined after TD. Wilcoxon signed rank test and Spearman ρ correlation were adapted for analyses of the results.The TD procedure reduced total and free plasma tryptophan effectively. After TD, the sympathetic nervous activity increased and parasympathetic nervous activity decreased. Baseline anxiety ratings positively correlated with post-TD changes in sympathetic nervous activity, VAS ratings, and physical symptoms. However, a negative correlation with post-TD changes in parasympathetic nervous activity was found.The change in ANS function after TD was associated with the severity of anxiety in healthy volunteers. This supports the fact that the effect of anxiety on heart rate variability is related to serotonin vulnerability. Furthermore, it also shows that the subjective anxiety rating has a biological basis related to serotonin.

The readmission rate and medical cost of patients with schizophrenia after first hospitalization - A 10-year follow-up population-based study.

BACKGROUND: Hospital readmissions caused by relapse in patients with schizophrenia are associated with prognosis. Identifying individuals at high risk of readmission and providing interventions to lower the readmission rate are important. METHODS: Patients with schizophrenia who were hospitalized for the first time were recruited from the National Health Insurance Research Database from 2001 to 2010 (n=808, mean age 28.9years) and compared with matched controls. Data on the demographics, cost, and utilization of medical resources of patients who were readmitted were compared with non-readmitted patients. The readmission time curve was analyzed by the Kaplan-Meier method. RESULT: 570 (70.5%) patients were readmitted within 10years; the median time between admissions was 1.9years, and 25% of subjects were readmitted within 4months of the first hospitalization. There were no significant differences in age, gender, or length of hospitalization between the readmission and non-readmission groups. Taking into account all psychiatric medical services, the readmission group had a significantly higher mean frequency of care and a greater medical cost than the non-readmission group and matched controls. However, there were no significant differences with regard to non-psychiatric medical services. CONCLUSION: Schizophrenia has a high rate of readmission and high medical cost in naturalistic settings. In addition to the traditional hospital-based treatment model for patients with schizophrenia, the development of an effective intervention program is important, especially in the early years of the disease.

Comparison of cognitive deficits among drug-naive patients with schizophrenia and major depressive disorder.

BACKGROUND: Cognitive deficits have been well-established among patients with severe mental illness. The aim of this study was to clarify the patterns of cognitive deficits in drug-naive patients with schizophrenia and non-psychotic major depressive disorder (MDD) as compared with controls. METHODS: Thirty drug-naïve participants with schizophrenia, 30 counterparts with non-psychotic MDD, and 30 age-, sex-, and education years-matched healthy controls were recruited. Neuropsychological tests, including the Wisconsin Card Test (WCST), the Continuous Performance Test (CPT) and the Finger Tapping Test (FTT), were administered. RESULTS: Patients with schizophrenia performed more poorly than the patients with MDD and the normal controls in the WCST. The patients with schizophrenia and the patients with MDD both performed more poorly than the normal controls in the CPT. The patients with MDD also performed more poorly than the normal controls in the FTT. LIMITATIONS: The age of onset of MDD in this study was younger than in previous reports. The cross-sectional design, small sample sizes, and limited numbers of neuropsychological domains in this study are all obstacles to making a clear causal conclusion. CONCLUSIONS: These results revealed a distinct pattern of neurocognitive dysfunction among drug-naive patients with schizophrenia and MDD, which may imply different underlying neurobiological mechanisms in schizophrenia and MDD.

Lower availability of striatal dopamine transporter in generalized anxiety disorder: a preliminary two-ligand SPECT study.

Dopamine and serotonin have been indirectly found to be associated with generalized anxiety disorder (GAD). The aims of this study were to examine the availabilities of the striatal dopamine transporter (DAT) and the midbrain serotonin transporter (SERT) in patients with GAD. 12 patients with GAD and 12 sex-matched, age-matched, and smoking status-matched healthy controls were recruited. The availabilities of DAT and SERT were approximated using single-photon emission computed tomography, with [Tc]TRODAT-1 and [I]ADAM as the ligands. There were several missing data for six participants with GAD in the ADAM study because of a lack of the radioligand at the time of the experiment. The DAT availability in the striatum was significantly lower in the patients with GAD than in the healthy controls. However, the SERT availability did not differ between the two groups. The results with respect to the striatal DAT level suggested a potential role in the pathophysiology of GAD.

The reductions in monetary cost and gains in productivity with methadone maintenance treatment: one year follow-up.

While methadone maintenance treatment (MMT) is beneficial for heroin dependence, there is little information regarding the reductions in monetary cost and gains in productivity following MMT. The aim of this study was to evaluate the changes in the monetary cost of heroin addiction and productivity after one year of MMT. Twenty-nine participants from an MMT clinic were included. The monetary cost, productivity, quality of life (QOL) and mental health status were assessed at both baseline and one year follow-up. The average annual total cost was approximately US$26,485 (1.43 GDP per capita in 2010) at baseline, and decreased by 59.3% to US$10,784 (0.58 GDP) at follow-up. The mean number of months of unemployment dropped from 6.03 to 2.79, the mean income increased to exceed the basic salary, but only reached 45.3% of the national average monthly earnings. The participants׳ mental health improved, but their QOL scores did not increase significantly. After one year of MMT, the monetary cost of heroin addiction fell, both the productivity and mental health of the participants׳ improved, but limited gains were seen with regard to their QOL.

Sex-specific associations between plasma oxytocin levels and schizotypal personality features in healthy individuals.

OBJECTIVES: Oxytocin (OT) has been shown to play a crucial role in the biology of social interaction. Sex differences associated with this neuropeptide system have been reported. OT may serves as an indicator of interpersonal stress, especially in women. The aim of this study was to investigate the sex-specific associations between plasma OT levels and schizotypal personality features, especially in interpersonal dimension, in healthy individuals. METHODS: Ninety six healthy participants, including 41 males and 55 females, were recruited. Fasting blood samples were analyzed by enzyme immunoassay of OT. The Schizotypal Personality Questionnaire (SPQ) was administered. Mann-Whitney U test was used to test the difference between male and female. Spearman's ρ correlation analysis (two-tailed) was carried out to examine the association between OT level and SPQ score. RESULTS: The results showed that OT level was significantly positively correlated with total score and interpersonal dysfunction dimensional scores of the SPQ only in females. CONCLUSIONS: Although the causal relationship remains unclear, our findings provide further evidence to support the sexual dimorphic role of OT in interpersonal biology. Moreover, the effect of sex difference also is taken into consideration.

Probing the association between dexamethasone-induced cortisol suppression and serotonin transporter availability among drug-free patients with major depressive disorder--a small-sample SPECT study with [¹²³I]ADAM.

The association between hypothalamo-pituitary-adrenal (HPA) axis function and the serotonergic system could be involved in the mechanism of depression. However, neuroimaging evidence is scarce. The aim of the present study was to probe the association between dexamethasone suppression test response and serotonin transporter (SERT) availability in drug-free patients with major depressive disorder (MDD). Seventeen MDD patients (five males and twelve females) were recruited. SPECT with [(123)I] ADAM was used to measure the midbrain SERT availability, and HPA axis function was measured by the dexamethasone suppression test (DST). The association was significant when considering all participants (ρ=0.69, p=0.002). This association may have clinical implications for the treatment of MDD.