Search

Background Long-term opioid and amphetamine-type stimulants (ATS) abuse may affect immunological function and impair executive function. We aimed to determine whether biomarkers of inflammation and executive function were associated with substance use in individuals with opioid use disorder (OUD) and ATS use disorder (ATSUD). The interactions between these biomarkers were also explored. Methods We assessed plasma cytokines [tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-8, IL-6, transforming growth factor (TGF)-β1, brain-derived neurotrophic factor (BDNF), and executive function in terms of the Wisconsin Card Sorting Test (WCST) and Continuous Performance Test (CPT) in OUD and ATSUD patients and healthy controls (HC). OUD and ATSUD patients were followed for 12 weeks, and their urine morphine and amphetamine tests, cytokine levels, and executive function were repeatedly measured. Results We enrolled 483 patients and 145 HC. Plasma TNF-α, CRP, IL-8, IL-6, and BDNF levels and most subscale scores on the WCST and CPT significantly differed between OUD and ATSUD patients and HC. Increased TNF-α levels and more perseveration error on the WCST were significantly associated with more urine drug-positive results and less abstinence. Plasma IL-6 and CRP levels were significantly negatively correlated with WCST and CPT performance. Conclusion OUD and ATSUD patients had more inflammation and worse executive function than HC. Inflammatory markers and WCST performance were associated with their urinary drug results, and higher inflammation was associated with poor executive function. Studies on regulating the inflammatory process and enhancing executive function in OUD and ATSUD are warranted.

BackgroundThe hyper-function of the striatal dopamine system has been suggested to underlie key pathophysiological mechanisms in schizophrenia. Moreover, patients have been observed to present a significant elevation of dopamine receptor availability compared to healthy controls. Although it is difficult to measure dopamine levels directly in humans, neurochemical imaging techniques such as single-photon emission computed tomography (SPECT) provide indirect indices of in vivo dopamine synthesis and release, and putative synaptic levels.MethodsWe focused on the role of dopamine postsynaptic regulation using [123I] iodobenzamide (IBZM) SPECT. We compared D2/3 receptor availability between 53 healthy controls and 21 medication-naive patients with recent-onset schizophrenia.ResultThe mean specific striatal binding showed no significant difference between patients and controls (estimated difference = 0.001; 95% CI −0.11 to 0.11; F = 0.00, df = 1, 69; p = 0.99). There was a highly significant effect of age whereby IBZM binding declined with advancing age [estimated change per decade of age = −0.01(binding ratio); 95% CI −0.01 to −0.004; F = 11.5, df = 1, 69; p = 0.001]. No significant correlations were found between the mean specific striatal binding and psychopathological or cognitive rating scores.ConclusionsMedication-naïve patients with recent-onset schizophrenia have similar D2/3 receptor availability to healthy controls. We suggest that, rather than focusing exclusively on postsynaptic receptors, future treatments should target the presynaptic control of dopamine synthesis and release.

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-naive, 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-naive 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.

Background: Repetitive transcranial magnetic stimulation (rTMS) shows potential therapeutic effects for individuals with addiction, but few studies have examined individuals with opioid use disorde...

Objectives Chronic inflammation and neuroprogression underlie bipolar disorder (BP) and associated cognitive deficits. Memantine (MM) exerts neuroprotective effects by reducing neuroinflammation. Therefore, we investigated whether add-on low-dose MM (5 mg/day) in BP-II patients may improve cognition and inflammation. Methods We combined two 12-week randomized, double-blind, placebo-controlled studies (NCT 01188148 and NCT 03039842) for analysis. Each participant was allocated to the MM or placebo group. Symptom severity, neuropsychological tests, and the cytokine plasma levels [tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukin-8 (IL-8), transforming growth factor-β1 (TGF-β1), and brain-derived neurotrophic factor (BDNF)] were evaluated at baseline and endpoint. A subgroup analysis of middle- to old-aged BP-II patients was also performed. Results We recruited 155 BP-II patients (23 of which were middle- to old-aged) for the MM group and 170 patients (20 of which were middle- to old-aged) for the placebo group. Add-on MM did not result in significant improvements in cognitive functions in all BP-II patients, but a group difference in TNF-α levels was found in the MM group (P=0.04). Specifically, in middle- to old-aged BP-II patients, there was a significant time and group interaction effect on omission T-scores, hit reaction time T-scores, and hit reaction time standard error T-scores on continuous performance tests (CPTs) in the MM group (P=0.007, 0.02, and 0.01, respectively), and a decrease in plasma TNF-α levels (P=0.04). Limitations The sample size of middle- to old-aged BP-II patients were limited. Conclusion Add-on MM may attenuate inflammation in BP-II and improve cognition in middle- to old-aged BP-II patients.

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.

Although patients with schizophrenia are well-known to exhibit significant brain volume reduction and cognitive function impairment, it remains unclear as to whether the reduction/impairment is correlated with dopaminergic activity under drug-naïve conditions.51 drug-naïve patients with and 128 healthy subjects were recruited in this study. DAT by [A significantly lower DAT availability existed in the drug-naïve group as compared with the healthy subjects (1.67 ± 0.45 vs. 1.98 ± 0.37, P0.005). DAT availability was significantly positively correlated with GMV in the left middle frontal lobe (r = 0.58, P0.005), the GMV being significantly reduced in the patients with schizophrenia (0.45 ± 0.10 vs. 0.49 ± 0.07, P0.005). Furthermore, the GMV in the left middle frontal lobe was significantly and positively correlated with full IQ (r = 0.34, P = 0.02) in the patients with schizophrenia, but not in the controls.Dysregulated dopaminergic activity may modulate volume variation in specific brain areas, and brain volume might alter IQ in drug-naïve patients with schizophrenia.

Objective Patients with opioid use disorder (OUD) have impaired attention, inhibition control, and memory function. The aldehyde dehydrogenase 2(ALDH2) gene has been associated with OUD and ALDH2 gene polymorphisms may affect aldehyde metabolism and cognitive function in other substance use disorder. Therefore, we aimed to investigate whether ALDH2 genotypes have significant effects on neuropsychological functions in OUD patients undergoing methadone maintenance therapy (MMT). Methods OUD patients undergoing MMT were investigated and followed-up for 12 weeks. ALDH2 gene polymorphisms were genotyped. Connors' Continuous Performance Test (CPT) and the Wechsler Memory Scale-Revised (WMS-R) were administered at baseline and after 12 weeks of MMT. Multivariate linear regressions and generalized estimating equations (GEEs) were used to examine the correlation between the ALDH2 genotypes and performance on the CPTs and WMS-R. Results We enrolled 86 patients at baseline; 61 patients completed the end-of-study assessments. The GEE analysis showed that, after the 12 weeks of MMT, OUD patients with the ALDH2 *1/*2＋*2/*2 (ALDH2 inactive) genotypes had significantly higher commission error T-scores (p= 0.03), significantly lower hit reaction time T-scores (p= 0.04), and significantly lower WMS-R visual memory index scores (p= 0.03) than did patients with the ALDH2 1*/*1 (ALDH2 active) genotype. Conclusion OUD patients with the ALDH2 inactive genotypes performed worse in cognitive domains of attention, impulse control, and memory than did those with the ALDH2 active genotype. We conclude that the ALDH2 gene is important in OUD and is associated with neuropsychological performance after MMT.

Objectives: Depression with partial remission and residual symptoms following treatments is common. Elucidating the problems remaining in the remitted patients would help optimize treatment. In this study, we intended to study remission rate and related factors as well as their unresolved problems in patients with treated depressive disorder. Methods: We included 65 medicated patients with depression for 6–12 months. We also chose 65 healthy persons as a control group. The study participants completed Beck Depression Inventory (BDI), checklists of side effects, Sheehan Disability Scale, World Health Organization Quality-of-Life-brief version, and Pittsburgh Sleep Quality Index (PSQI). Remission was defined as a BDI score of ≤ 15. Results: We found that the PSQI score was still higher in the remission group than the control group. Conclusion: Sleep problems, which may still be a commonly unresolved problem in medicated patients with depression, should be noticed by clinicians.

Purpose Loneliness is a subjective feeling by which an individual perceives a lack of closeness in interpersonal relationships. An isolated living status is linked with higher odds of risky health behavior. The conflicting impacts of loneliness and isolated living status on stress-related biomarkers, depressive symptoms, and disability remain unexplained. Methods Six hundred twenty-nine participants aged 66.0 (SD=7.3) separated into four groups: “Lonely and Isolated,” “Not Lonely, but Isolated,” “Lonely, but Not Isolated,” and “Neither Lonely, nor Isolated,” were retrieved from the Social Environment and Biomarkers of Aging Study conducted in 2000. Follow-up health indicators in 2006 included three stress-related biomarkers, depressive symptoms, and two physical disability indicators. A hierarchical regression was performed for the analysis. Results Firstly, compared to the “Neither Lonely nor Isolated” group, only the “Lonely, but Not Isolated” participants at baseline retained positive associations with the stress-related biomarkers levels 6 years later (urine cortisol level (B=9.25, 95% CI=3.24-15.27), serum Interleukin-6 level (B=2.76, 95% CI=0.72-4.79) and the serum high sensitivity C-reactive protein (hsCRP) level (B=0.40, 95% CI=0.17-0.62)). However, such associations were not observed in the “Lonely and Isolated” participants. Secondly, only “Lonely and Isolated” participants at baseline were positively associated with depressive symptoms 6 years later (B=1.70, 95% CI=0.11-3.30). Finally, the associations between combinations of loneliness and isolated living status and physical disability were eliminated after adjusting the covariables. Conclusion Four combinations of loneliness and isolated living status were associated with different impacts on stress-related biomarkers, depressive symptoms, and physical disability. Further dynamic investigations are warranted.

Background Treatment-resistant schizophrenia (TRS) and non-TRS may be associated with different dopaminergic and glutamatergic regulations. The concept of dysregulated glutamatergic concentrations in specific brain regions remains controversial. Herein, we aimed to assess (i) the distribution of the glutamatergic concentration in the brain, (ii) the association between working memory (WM) differences in TRS and non-TRS patients, and (iii) whether an alteration in the glutamate (Glu) level is associated with WM. Methods The participants included 38 TRS patients, 35 non-TRS patients, and 19 healthy controls (HCs), all of whom underwent 1.5-Tesla proton magnetic resonance spectroscopy of anterior cingulate cortex (ACC) and medial prefrontal cortex (MPFC). The ratios of glutamatergic neurometabolites to N-acetylaspartate + N-acetyl aspartylglutamate (NAAx) were calculated. Cognitive function was assessed using the Wechsler Adult Intelligence Scales, 4th Edition, which included the working memory index (WMI). Result The TRS patients had a higher glutamate + glutamine (Glx)/NAAx ratio compared to the non-TRS patients and HCs in the ACC, but this was not significantly different in the MPFC. WM was negatively correlated with Glx/NAAx in the ACC among the non-TRS patients, but not in the TRS patients or HCs. Conclusions Our findings were consistent with most studies indicating that the glutamatergic concentration in the ACC plays important roles in the classification of TRS and cognition. Our results may provide potential evidence for predictors and treatment response biomarkers in TRS patients. Further research is needed to probe the value using the relationship between Glu and WM as a potential prognostic predictor of schizophrenia.

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.

Objective The present study aimed to detect differences in the reward response between adults with attention deficit hyperactivity disorder (ADHD) and healthy controls (HCs) using functional magnetic resonance imaging (fMRI). Methods The Iowa gambling task (IGT) was designed to explore participants’ reward-related decision-making in relation to selections during risky behaviors. Twenty adults with ADHD and 20 HCs were enrolled. fMRI with a modified IGT was performed. Results The adults with ADHD showed a poorer performance in terms of avoidance during risky behaviors. The fMRI results indicated that the adults with ADHD had significantly lower orbitofrontal cortex (OFC) activation. A positive correlation between performance in the IGT and brain activation in the OFC was detected. Conclusions The results suggested that the adults with ADHD exhibited abnormal OFC responses during decision-making. Significance To the best of our knowledge, this is the first study to use fMRI to collect brain activation data while performing the IGT in adults with ADHD. Our findings suggest that deficits in reward processing in ADHD are still present during adulthood.

Objective: Few studies have examined the outcome predictors in methamphetamine (MA) use disorder patients referred from the justice system. Craving and personality trait, such as novelty seeking (NS) and harm avoidance (HA), have important roles in developing and sustaining addiction. Therefore, we investigated whether craving severity and personality traits are correlated with the MA use disorder treatment outcomes in those under the deferred prosecution status. Methods: We measured craving levels and personality traits of NS and HA at the beginning of a one-year treatment program for MA use disorder. We monitored urinary MA/amphetamine results during the one-year treatment program. Multiple linear regressions were used to examine the correlation between craving severity, personality traits, and MA use disorder treatment outcomes. Results: We first enrolled 98 patients, but only 56 patients completed the end-of-treatment assessments. We did not find any association between craving severity, personality traits, and MA treatment outcomes in those populations. But we found that age and percentage of positive urine MA/amphetamine results were significantly related to treatment completion (p ＜ 0.05). Higher percentages of positive urine MA/amphetamine results were also significantly associated with shorter treatment duration (p = 0.01). In addition, positive urine results at baseline were significantly associated with higher percentages of positive urine tests in the following treatment course (p = 0.001). Conclusion: Our study data did not find that craving severity and personality traits were associated treatment outcomes in this special population. But urine MA/amphetamine results were more related with completion of programs. Further studies to evaluate the treatment outcomes and other potential outcome predictors in those were referred from the justice system are needed.

Patients with schizophrenia have difficulties in social cognitive domains including emotion recognition and mentalization, and in sensorimotor processing and learning. The relationship between social cognitive deficits and sensorimotor function in patients with schizophrenia remains largely unexplored. With the hypothesis that impaired visual motor processing may decelerate information processing and subsequently affects various domains of social cognition, we examined the association of nonverbal emotion recognition, mentalization, and visual motor processing in schizophrenia. The study examined mentalization using the verbal subset of the Chinese version of Theory of Mind (CToM) Task, an equivalent task of the Faux Pas Test; emotion recognition using the Diagnostic Analysis of Nonverbal Accuracy 2-Taiwan version (DANVA-2-TW), and visual motor processing using a joystick tracking task controlled for basic motor function in 34 individuals with chronic schizophrenia in the community and 42 healthy controls. Patients with schizophrenia had significantly worse performance than healthy controls in social cognition, including facial, prosodic emotion recognition, and mentalization. Visual motor processing was also significantly worse in patients with schizophrenia. Only in patients with schizophrenia, both emotion recognition (mainly in prosodic modality, happy, and sad emotions) and mentalization were positively associated with their learning capacity of visual motor processing. These findings suggest a prospective role of sensorimotor function in their social cognitive deficits. Despite that the underlying neural mechanism needs further research, our findings may provide a new direction for restoration of social cognitive function in schizophrenia by enhancing visual motor processing ability.

The hyper-function of the striatal dopamine system has been suggested to underlie key pathophysiological mechanisms in schizophrenia. Moreover, patients have been observed to present a significant elevation of dopamine receptor availability compared to healthy controls. Although it is difficult to measure dopamine levels directly in humans, neurochemical imaging techniques such as single-photon emission computed tomography (SPECT) provide indirect indices ofWe focused on the role of dopamine postsynaptic regulation using [The mean specific striatal binding showed no significant difference between patients and controls (estimated difference = 0.001; 95% CI -0.11 to 0.11;Medication-naïve patients with recent-onset schizophrenia have similar D

The impact of serotonergic system on obsessive-compulsive disorder (OCD) is well studied. However, the correlation between OC presentations and autonomic nervous system (ANS) is still unclear. Furthermore, whether the correlation might be modulated by serotonin is also uncertain.We recruited eighty-nine healthy subjects. Serotonin transporter (SERT) availability by [The interactions were significant in the factors of low frequency (LF), high frequency (HF), and root mean square of successive differences (RMSSD). Furthermore, the significantly negative correlations between OC symptoms and the above HRV indexes existed only in subjects with higher SERT availability.OC symptoms might be correlated with ANS regulations in subjects with higher SERT availability.

Background Dissociative symptoms have been constantly found in schizophrenia (SCZ). Traumatic experience seems to relate to dissociative symptoms and brain volume alterations in SCZ. The current study aimed to clarify the inter-relations of dissociative symptoms, traumatic experience, and brain volume in SCZ. Methods We employed voxel-based morphometry to compare the distributions of gray matter volumes (GMV) in 37 SCZ patients and 26 healthy volunteers (HV). All participants underwent T1-weighted images on a 1.5 T MRI system. Traumatic experience was examined by the Brief Betrayal Trauma Survey. Pathological and non-pathological dissociation were measured by the Dissociative Symptoms Scale and the Dissociative Experiences Scale, respectively. Results A GMV reduction was found in SCZ patients in the right thalamus. Importantly, a significant group by pathological dissociation interaction was observed in the medial frontal cortex (MFC), bilateral anterior insular area, and precuneus. A negative correlation between MFC/insular GMV and pathological dissociation was observed in HV; higher non-pathological dissociation and smaller volume in MFC/insula were associated with pathological dissociation. In contrast, higher traumatic experience, higher non-pathological dissociation, and larger volume in MFC/insula were associated with pathological dissociation in SCZ. Conclusion The negative association between MFC/insula GMV and pathological dissociation in HV was not observed in SCZ patients. The absent negative association in SCZ suggests a unique neural underpinning in SCZ with dissociative pathology, in which medial frontal and temporal regions play crucial roles.

Collapsin response mediator protein 5 (CRMP5), a member of the CRMP family, is expressed in the brain, particularly in the hippocampus, an area of the brain that can modulate stress responses. Social stress has a well-known detrimental effect on health and can lead to depression, but not all individuals are equally sensitive to stress. To date, researchers have not conclusively determined how social stress increases the susceptibility of the brain to depression. Here, we used the chronic social defeat stress (CSDS) model and observed higher hippocampal CRMP5 expression in stress-susceptible (SS) mice than in control and stress-resilient (RES) mice. A negative correlation was observed between the expression levels of CRMP5 and the social interaction (SI) ratio. Reduced hippocampal CRMP5 expression increased the SI ratio in SS mice, whereas CRMP5 overexpression was sufficient to induce social avoidance behaviors in control mice following exposure to subthreshold social stress induced by lentivirus-based overexpression and inducible tetracycline-on strategies to upregulate CRMP5. Interestingly, increased CRMP5 expression in SS and lenti-CRMP5-treated mice also caused serum corticosterone concentrations to increase. These findings improve our understanding of the potential mechanism by which CRMP5 triggers susceptibility to social stress, and they support the further development of therapeutic agents for the treatment of stress disorders in humans.

Treatment-resistant schizophrenia (TRS) is one of the subgroups of schizophrenia of which little is known with regard to its optimal mechanism. Treatment response, either as full remission of symptoms or prediction by biomarker, is important in psychiatry. We have proposed a model that integrates dopaminergic and glutamatergic systems with the biological interactions of TRS patients. We hypothesize that the subgroups of schizophrenia may be determined by glutamatergic and dopaminergic concentrations prior to medical treatment. This hypothesis implies that higher glutamatergic concentration in the brain with normalized or decreased dopamine synthesis capacity may explain aspects of TRS as observed in clinical medical practice, neuroimaging measurements, and brain stimulations. According to this hypothesis, the ability to prescribe a proper medication combination, to predict the outcome in first-episode psychosis, and personalized medicine for chronic schizophrenia patients can be applied into practice. This represents an initial step in explaining psychosis due to the valence of two neurotransmitters. Future studies are needed to examine the validity of this mechanism.

Transcranial direct current stimulation (tDCS) could be a potential treatment for nicotine dependency. Little is known with regards to the efficacy of this treatment in cigarette-smoking patients with heroin dependency. In this sham-controlled study, we probed the effect of 5-day, 20-min, 2-mA-intensity tDCS treatment on the outcomes of cigarette-smoking. Our objectives are to examine the effects of tDCS on two outcomes: objective expired CO concentration and subjective self-reported number of cigarettes smoked per day. A total of 30 patients were randomized into active or sham control groups. The stimulation site was randomized to anodal stimulation of the left dorsal lateral prefrontal cortex or the orbital frontal cortex. The expired CO concentration was recorded. The patients also reported their cigarette consumption and level of craving prior to each 5-day treatment period and after 5 days of follow-up. tDCS was found to be effective in terms of reducing the expired CO concentration, and both groups demonstrated reduced numbers of cigarettes smoked. However, no significant group difference was found with regards to craving tendency. tDCS may affect objective outcomes related to cigarette-smoking among patients with heroin dependence.

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.

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.

Antisocial personality disorder (ASPD) is highly comorbid with substance use disorders (SUDs). We hypothesize that chronic neuroinflammation and the loss of neurotrophic factors prompts the pathogenesis of both disorders. We used ELISA to measure plasma levels of proinflammatory (tumor necrosis factor-α [TNF-α], C-reactive protein [CRP]) and anti-inflammatory factors (transforming growth factor-β1 [TGF-β1] and interleukin-10 [IL-10]), and brain-derived neurotrophic factor (BDNF) in male patients with ASPD (n=74), SUDs (n=168), ASPD comorbid with SUDs (ASPD+SUDs) (n=438), and Healthy Controls (HCs) (n=81). A multivariate analysis of covariance (MANCOVA) controlled for possible confounders was used to compare cytokines and BDNF levels between groups. The results of MANCOVA adjusted for age showed a significant (p

ObjectivePrevious studies have indicated that there is dopamine transporter (DAT) dysregulation and P300 abnormality in adults with attention-deficit hyperactivity disorder (ADHD); however, the correlations among the three have not been fully explored.MethodsA total of 11 adults (9 males and 2 females) with ADHD and 11 age-, sex-, and education-level-matched controls were recruited. We explored differences in DAT availability using single-photon emission computed tomography and P300 wave of event-related potentials between the two groups. The correlation between DAT availability and P300 performance was also examined.ResultsDAT availability in the basal ganglia, caudate nucleus, and putamen was significantly lower in the ADHD group. Adults with ADHD had lower auditory P300 amplitudes at the Pz and Cz sites, as well as longer Fz latency than controls. DAT availability was negatively correlated to P300 latency at Pz and Fz.ConclusionsAdults with ADHD had both abnormal DAT availability and P300 amplitude, suggesting that ADHD is linked to dysfunction of the central dopaminergic system and poor cognitive processes related to response selection and execution.

Objectives: We investigated the association of the aldehyde dehydrogenase 2 ( ALDH2) polymorphism (rs671), which is involved with the dopaminergic function, and with changes in cytokine levels and cognitive function, in a 12-week follow-up study in patients with bipolar disorder. Methods: Patients with a first diagnosis of bipolar disorder were recruited. Symptom severity and levels of plasma cytokines (tumor necrosis factor α, C-reactive protein, interleukin 6 and transforming growth factor β1) were examined during weeks 0, 1, 2, 4, 8 and 12. Neurocognitive function was evaluated at baseline and endpoint. The ALDH2 polymorphism genotype was determined. Results: A total of 541 patients with bipolar disorder were recruited, and 355 (65.6%) completed the 12-week follow-up. A multiple linear regression analysis showed a significant ( p = 0.000226) association between the ALDH2 polymorphism and changes in C-reactive protein levels. Different aspects of cognitive function improved in patients with different ALDH2 genotypes. Only patients with the ALDH2*1*1 genotype showed significant correlations between improvement of cognitive function and increased transforming growth factor -β1. Conclusion: The ALDH2 gene might influence changes in cytokine levels and cognitive performance in patients with bipolar disorder. Additionally, changes in cytokine levels and cognitive function were correlated only in patients with specific ALDH2 genotypes.

Aim Clozapine-associated fever is common but the specific cytokine changes and treatment durations that may cause fever remain unknown. We investigated the association between inflammatory cytokine changes and clozapine-induced fever in patients who were treated with clozapine. Methods Forty-three patients with schizophrenia or schizoaffective disorder, diagnosed by using the Chinese Version of the Mini International Neuropsychiatric Interview, were treated with clozapine for the first time (first-time use group, n = 22) or for more than 6 months (long-term use group, n = 21). The Positive and Negative Syndrome Scale, tympanic temperature, and levels of tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), interleukin-2 (IL-2), and interleukin-6 (IL-6) were determined at baseline and weeks 1, 2, 3, 4, and 6. A multiple linear regression with generalized estimating equation methods was used to analyze the association between the changes in the cytokine levels and clozapine-induced fever in the different groups. Results The IL-6 level changes were significantly different between the two groups (P = 0.04). In the first-time use group, the fever rate was increased (47.1%) compared with the long-term use group (5.6%, P = 0.005). Moreover, in these patients, the TNF-α, INF-γ, IL-2, and IL-6 levels were significantly (P < 0.001) different from patients who did not develop a fever. An interaction effect with the different treatment duration groups and fever development was only significant for IL-6 (P < 0.001). Conclusion Patients who were treated with clozapine for the first time have an increased rate of developing a fever, and IL-6 might have a specific role in the interaction effect between treatment duration and fever development.

Background The outcome of methadone maintenance therapy (MMT) varies in each patient with opioid use disorder (OUD). Opioid abuse activates proinflammatory processes by increasing cytokine production and impairing neurotrophic factor expression, and possibly leads to a vicious cycle that hinders recovery. Therefore, we investigated whether markers of inflammation and neurotrophic expression correlate with the MMT outcomes in OUD patients. Method We investigated OUD patients undergoing MMT and followed them up for 12 weeks. We measured plasma tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-6, IL-1β, transforming growth factor (TGF)-β1, brain-derived neurotrophic factor (BDNF), urinary morphine tests, and plasma morphine levels at baseline and on weeks 1, 4, 8, and 12 during MMT. Multiple linear regressions and generalized estimating equations (GEEs) were used to examine the correlation between the cytokine and BDNF levels and MMT outcomes. Results We initially enrolled 104 patients, but only 78 patients completed end-of-study assessments. Plasma levels of CRP, TGF-β1, and BDNF fell during MMT. Plasma IL-6 levels were significantly associated with plasma morphine levels (P = 0.005) and urinary morphine-positive (+) results (P = 0.04), and significantly associated with poor compliance (P = 0.009) and early dropout from MMT (P = 0.001). However, other cytokine and BDNF levels were not consistently associated with MMT outcomes. Conclusion Higher IL-6 levels were associated with poor MMT outcomes. Additional studies on regulating IL-6 expression to improve treatment outcomes in OUD patients might be warranted.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by several behavioral disturbances, especially cognitive decline and deficits in social competence. Previous studies revealed that decreased social activity would accelerate AD progression, whereas enhanced social interaction could rescue AD-induced memory impairment. Collapsin response mediator protein 5 (CRMP5), which belongs to a family of cytosolic proteins, is abundantly expressed in the brain and is involved in the regulation of neurodevelopment and the pathology of several neuropsychiatric diseases. However, the functions of CRMP5 in AD are still unclear. Here, we demonstrated that 9-month-old 3xTg-AD mice exhibited social behavioral deficits and increased hippocampal CRMP5 levels compared to control (B6129S) mice. Knockdown of CRMP5 reversed the social deficits in 9-month-old 3xTg-AD mice, whereas CRMP5 overexpression decreased social interaction in both 3xTg-AD and control mice at 6 months of age. Interestingly, decreased expression of CRMP5 rescued AD-induced memory impairment, but overexpression of CRMP5 accelerated memory loss only in 3xTg-AD mice. In addition, we found that CRMP5 could regulate surface GluA2 and GluA2 S880 phosphorylation. These results suggest that CRMP5 regulates social behavior via modulation of surface GluA2 trafficking and affects memory performance in 3xTg-AD mice.

It has been proposed that the dopaminergic system and heritability may play roles in attention deficit/hyperactivity disorder (ADHD). We assessed the performance of healthy parents of children with ADHD in the finger tapping test (FTT) in this study, which is a reliable test and sensitive to central dopamine activity. A total of 16 parents of children with ADHD and 32 controls were enrolled. The FTT was conducted. The 16 healthy parents of children with ADHD exhibited a significantly poorer performance in the FTT, using the nondominant hand, than the 32 healthy controls. This finding indicated that poor motor function could be a potential characteristic in parents of offspring with ADHD.

AIM: Our study aimed to explore whether anxiety disorders were associated with certain physical illnesses as previous studies mentioned or a greater number of comorbid anxiety disorders would influence the physical illnesses in the elderly by the population-based analyses. METHODS: Using the National Health Insurance Research Database (NHIRD), we included subjects aged over 60 years. Nine hundred and fifty four subjects with anxiety disorders defined by ICD-9-CM and 4770 control subjects without anxiety disorders were included. The odds ratios (ORs) were calculated for the risks of physical illnesses in the both groups. RESULTS: Subjects with anxiety disorders had higher ORs of cardiovascular disease (OR = 1.33-2.80), cerebrovascular disease (OR = 2.07), peptic ulcer (OR = 3.41), and hyperlipidemia (OR = 2.99). Furthermore, a greater number of comorbid anxiety disorders may further increase the ORs of the physical illnesses aforementioned except the peripheral vascular disorder when compared to those without anxiety disorders. CONCLUSIONS: Elderly subjects with more anxiety disorders may be associated with vascular and metabolic problems. Carefully assessing the physical illnesses for the elderly with anxiety disorders should be aware in the clinical practice. Language: en