The association between abused adults and substance abuse in Taiwan, 2000-2015.

OBJECTIVE: To investigate whether adults suffering from violence were at risk of substance abuse and provides insight into the relationship between male and female abusers and substance abuse from 2000 to 2015 in Taiwan. METHODS: This study used data on outpatient, emergency, and inpatient visits for 2 million people enrolled in universal health insurance from 2000 to 2015. ICD-9 diagnosis codes 995.8 (abused adult) and E960-E969 (homicide and injury purposely inflicted by other persons) were defined in this case study, analyzing first-time violence in adults aged 18-64 (study group). Non-abused patients (control group) were matched in a 1:4 ratio, and the paired variables were gender, age (± 1 year), pre-exposure Charlson Comorbidity Index, and year of medical treatment. SAS 9.4 and Cox regression were used for data analysis. RESULTS: A total of 8,726 people suffered violence (control group: 34,904 people) over 15 years. The prevalence of substance abuse among victims of violence was 78.3/104, 61.9/104, and 51.5/104 for tobacco use disorder, alcoholism, and alcohol abuse, respectively. The risk (adults, overall) of drug abuse, drug dependence, and alcoholism after exposure to violence (average 9 years) was 7.47, 7.15, and 6.86 times (p < 0.01), respectively, compared with those without violence. The risk (adults, males) of drug abuse, drug dependence, and alcohol abuse after exposure to violence (average 9 years) was 6.85, 6.27, and 6.07 times, respectively, higher than those without violence (p < 0.01). Risks of drug dependence, alcohol abuse and alcoholism (adults, females) after exposure to violence (average 9 years) were 14.92, 12.26, and 11.55 times, respectively, higher than non-abused ones (p < 0.01). CONCLUSION: The risks of substance abuse, after adult violence, are higher than in those who have not suffered violent injuries.

Effects of Early Risperidone Treatment on Metabolic Parameters in Socially Isolated Rats-Implication of Antipsychotic Intervention across Developmental Stages of Schizophrenia.

BACKGROUND: Second-generation antipsychotics (SGAs) is thought responsible for the metabolic abnormalities of schizophrenic patients, however, some untreated schizophrenic patients had already developed problems with glucose metabolism. The present study examined the hypothesis that schizophrenia itself but not risperidone, an extensively employed SGA, is accountable for metabolic abnormalities. METHODS: A 56-day risperidone regimen (1 mg/kg/day) was employed for rats of social isolation rearing (SIR) beginning at different developmental stage (28 or 56 days after weaning, i.e., adolescent and young adulthood, respectively). Metabolic parameters including body weight, systolic blood pressure (SBP), triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, and plasma glucose were measured at baseline, 28, and 56 days of the regimen. Oral glucose tolerance test (OGTT) was performed at the end of the regimen. Insulin function was evaluated by area under the curve (AUC) of OGTT, homeostasis model assessment-insulin resistance (HOMA-ir), and Matsuda index. RESULTS: Our results demonstrated that: (i) SIR rats presented higher body weight, plasma triglyceride, and HOMA-ir than social controls. (ii) Higher insulin resistance was specifically presented in young adult rather than adolescent SIR rats. (iii) Adolescent drugged rats showed a lower level of LDL in day 28 of the regimen than young adult. Risperidone led to a lower LDL level in only young adult IR rats in day 56 than undrugged rats. (iv) SIR-induced dysregulation of insulin can be reversed by chronic risperidone treatment beginning at adolescence but not young adulthood. CONCLUSIONS: Our findings support the primary role of schizophrenia in metabolic abnormalities and risperidone appear beneficial when administered earlier.

Resting-State EEG Connectivity at High-Frequency Bands and Attentional Performance Dysfunction in Stabilized Schizophrenia Patients.

Background and Objectives: Attentional dysfunction has long been viewed as one of the fundamental underlying cognitive deficits in schizophrenia. There is an urgent need to understand its neural underpinning and develop effective treatments. In the process of attention, neural oscillation has a central role in filtering information and allocating resources to either stimulus-driven or goal-relevant objects. Here, we asked if resting-state EEG connectivity correlated with attentional performance in schizophrenia patients. Materials and Methods: Resting-state EEG recordings were obtained from 72 stabilized patients with schizophrenia. Lagged phase synchronization (LPS) was used to measure whole-brain source-based functional connectivity between 84 intra-cortical current sources determined by eLORETA (exact low-resolution brain electromagnetic tomography) for five frequencies. The Conners' Continuous Performance Test-II (CPT-II) was administered for evaluating attentional performance. Linear regression with a non-parametric permutation randomization procedure was used to examine the correlations between the whole-brain functional connectivity and the CPT-II measures. Results: Greater beta-band right hemispheric fusiform gyrus (FG)-lingual gyrus (LG) functional connectivity predicted higher CPT-II variability scores (r = 0.44, p < 0.05, corrected), accounting for 19.5% of variance in the CPT-II VAR score. Greater gamma-band right hemispheric functional connectivity between the cuneus (Cu) and transverse temporal gyrus (TTG) and between Cu and the superior temporal gyrus (STG) predicted higher CPT-II hit reaction time (HRT) scores (both r = 0.50, p < 0.05, corrected), accounting for 24.6% and 25.1% of variance in the CPT-II HRT score, respectively. Greater gamma-band right hemispheric Cu-TTG functional connectivity predicted higher CPT-II HRT standard error (HRTSE) scores (r = 0.54, p < 0.05, corrected), accounting for 28.7% of variance in the CPT-II HRTSE score. Conclusions: Our study indicated that increased right hemispheric resting-state EEG functional connectivity at high frequencies was correlated with poorer focused attention in schizophrenia patients. If replicated, novel approaches to modulate these networks may yield selective, potent interventions for improving attention deficits in schizophrenia.

Age and sex differences on the association between anxiety disorders and obstructive sleep apnea: A nationwide case-control study in Taiwan.

AIM: The aim of this study was to examine the association between anxiety disorders and obstructive sleep apnea (OSA). METHODS: This is a population-based, retrospective case-control study using Taiwan's nationwide database. We included patients with OSA aged ≥12 years, diagnosed according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes: 327 and 780. Each enrolled patient with OSA needed to undergo a polysomnography examination within 1 year pre- or post-OSA occurrence. Patients with OSA and controls were selected in a 1:4 ratio. Patients with anxiety disorders (ICD-9-CM code 300) were diagnosed by board-certified psychiatrists and required to visit the outpatient clinic at least three times per year. Multivariate logistic regression and interaction analyses were used to evaluate the objective association. RESULTS: This study enrolled 7987 and 31 948 participants with and without OSA, respectively. A significant difference in anxiety exposure was observed only pre-OSA diagnosis but not post-OSA diagnosis. Compared with patients without anxiety disorders: (i) those with anxiety disorders had an adjusted odds ratio (aOR) of ≈1.864 in OSA comorbidity (aOR = 1.864; 95% confidence interval [CI] = 1.337-2.405); and (ii) subgroup analysis showed a significant interaction that anxiety patients of male sex, aged 18 to 44 years, aged 45 to 64 years, and hypertension had a higher aOR in OSA comorbidity (aOR = 2.104 [95% CI = 1.436-2.589], aOR = 1.942 [95% CI = 1.390-2.503], aOR = 2.179 [95% CI = 1.564-2.811], and aOR = 2.092 [95% CI = 1.497-2.706], respectively). CONCLUSION: The study revealed a higher ratio of previous anxiety exposure in patients with OSA. Compared with those without anxiety, anxiety patients of male sex, aged 18 to 64 years, and with hypertension had a higher risk of OSA comorbidity.

The Effects of Bi-Anodal tDCS Over the Prefrontal Cortex Regions With Extracephalic Reference Placement on Insight Levels and Cardio-Respiratory and Autonomic Functions in Schizophrenia Patients and Exploratory Biomarker Analyses for Treatment Response.

BACKGROUND: We previously showed the efficacy of bi-anodal transcranial direct current stimulation (tDCS) over the prefrontal cortex (PFC) regions with extracephalic reference placement in improving negative symptoms in schizophrenia. In this ancillary investigation, the effects of this intervention on insight levels, other clinical outcomes, and cardio-respiratory and autonomic functions were examined and the potential of biomarkers for treatment response was explored. METHODS: Schizophrenia patients were randomly allocated to receive 10 sessions of bi-anodal tDCS over the PFC regions with extracephalic reference placement (2 mA, 20 minutes, twice daily for 5 weeks) or sham stimulation. We examined, in 60 patients at baseline, immediately after stimulation and at follow-up visits, the insight levels, other clinical outcomes, blood pressure, respiratory rate, heart rate, and heart rate variability. RESULTS: Insight levels as assessed by the abbreviated version of the Scale to Assess Unawareness in Mental Disorder in schizophrenia awareness of the disease, positive and negative symptoms dimensions, and beliefs about medication compliance as assessed by Medication Adherence Rating Scale were significantly enhanced by active stimulation relative to sham. No effects were observed on cognitive insight, other clinical outcomes, or cardio-respiratory and autonomic functions. Heart rate variability indices as biomarkers were not associated with the clinical response to the intervention. CONCLUSIONS: Our results provide evidence for bi-anodal tDCS over the PFC regions with extracephalic reference placement in heightening the levels of insight into the disease and symptoms, as well as beliefs about medication compliance in schizophrenia, without impacting other clinical outcomes and cardio-respiratory/autonomic functions.

Eating disorders and the risk of esophageal and stomach cancers-A nationwide, population-based cohort study in Taiwan.

BACKGROUND: Previous studies have shown elevated cancer risk in anorexia nervosa but the literature on other eating disorders (EDs) is scarce. This study aimed to investigate the association between all EDs and esophageal, stomach, and other cancers. METHODS: We used a retrospective cohort design, based on a two-million randomized longitudinal health insurance dataset, a sub-dataset of Taiwan's National Health Insurance Research Database. From all the potential participants aged 20 years or more, a total of 6,628 participants were enrolled, including 1,657 patients with EDs, with sex-, age-, and indexed date-matched (1:3) 4,971 controls. Each participant was individually tracked from 2000 to 2015 to identify incident cases of cancers, including esophageal cancer (EC), stomach cancer (SC), and all other cancers (AOC). The multivariate Cox proportional hazards model was employed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between EDs and cancer. RESULTS: Of the total 6,628 enrollees, 222 in 1,657 individuals with EDs and 810 in the 4,971 non-ED control individuals developed cancer (1,262.40 vs. 1,472.15 per 100,000 person-years), and the Kaplan-Meier survival analysis was not statistically significant (log-rank, p = .324). However, after adjusting for covariates, the risk of EC and SC among the individuals with an ED was significantly higher, with adjusted HRs of 5.32 (95% CI: 1.07-26.49, p < .001) and 4.61 (95% CI: 1.91-11.14, p < .001), respectively. EDs were not associated with other cancers. CONCLUSIONS: This study provides evidence for the association between EDs and the risk for EC and SC. Further research on mechanisms and prevention is therefore needed.

Psychiatric disorders in female psychosexual disorders-a nationwide, cohort study in Taiwan : Psychiatric disorders and female psychosexual disorders.

We aimed to investigate whether females with psychosexual disorders were associated with the risk of affective and other psychiatric disorders. A total of 2240 enrolled individuals, with 560 patients with psychosexual disorders and 1680 subjects without psychosexual disorders (1:3) matched for age and index year, from the Longitudinal Health Insurance Database, retrieved from the National Health Insurance Research Database (NHIRD), between 2000 and 2015 in Taiwan. The multivariate Cox regression model was used to compare the risk of developing psychiatric disorders during the 15 years of follow-up. There were 98 in the cohort with psychosexual disorders (736.07 per 100,000 person-year) and 119 in the non-cohort without psychosexual disorders (736.07 per 100,000 person-year) that developed psychiatric disorders. The multivariate Cox regression model revealed that the adjusted hazard ratio (HR) was 9.848 (95% CI = 7.298 - 13.291, p < 0.001), after the adjustment of age, monthly income, urbanization level, geographic region, and comorbidities. Female patients with psychosexual disorders were associated with the risk of psychiatric disorders. This finding could be a reminder for clinicians about the mental health problems in patients with psychosexual disorders.

Posttraumatic stress disorder and the risk of erectile dysfunction: a nationwide cohort study in Taiwan : PTSD and erectile dysfunction.

BACKGROUND: This study aimed to investigate the association between posttraumatic stress disorder and the risk of developing erectile dysfunction. METHODS: In this population-based retrospective cohort study, we used Taiwan's National Health Insurance Research Database to analyze patients who were newly diagnosed with posttraumatic stress disorder (PTSD) between 2000 and 2013, with a 1:3 ratio by age and index year matched with patients in a non-PTSD comparison group, for the risk of erectile dysfunction. RESULTS: In total, 5 out of 1079 patients in the PTSD group developed erectile dysfunction, and 3 out of 3237 patients in the non-PTSD group (47.58 vs. 9.03 per 100,000 per person-year) developed erectile dysfunction. The Kaplan-Meier analysis showed that the PTSD cohort had a significantly higher risk of erectile dysfunction (log-rank, p < 0.001). The Cox regression analysis revealed that the study subjects were more likely to develop an injury (hazard ratio: 12.898, 95% confidence intervals = 2.453-67.811, p = 0.003) after adjusting for age, monthly income, urbanization level, geographic region, and comorbidities. Psychotropic medications used by the patients with PTSD were not associated with the risk of erectile dysfunction. CONCLUSIONS: Patients who suffered from PTSD had a higher risk of developing erectile dysfunction.

Attenuated vagally-mediated heart rate variability at rest and in response to postural maneuvers in patients with generalized anxiety disorder.

BACKGROUND: Altered heart rate variability (HRV), an index of autonomic nervous system function, has been reported in generalized anxiety disorder (GAD), but the results have been mixed. Thus, the present study, using a large sample size and better methodology, aims to examine whether GAD is associated with impaired HRV, both at rest and in response to posture challenges. METHODS: In total, 1832 participants were recruited in this study, consisting of 682 patients with GAD (including 326 drug- and comorbidity-free GAD patients) and 1150 healthy controls. Short-term HRV was measured during the supine-standing-supine test (5-min per position). Propensity score matching (PSM), a relatively novel method, was used to control for potential confounders. RESULTS: After PSM algorithm, drug- and comorbidity-free GAD patients had reductions in resting (baseline) high-frequency power (HF), an index for parasympathetic modulation, and increases in the low-frequency/HF ratio (LF/HF), an index for sympathovagal balance as compared to matched controls. Furthermore, the responses of HF and LF/HF to posture changes were all attenuated when compared with matched controls. Effect sizes, given by Cohen's d, for resting HF and HF reactivity were 0.42 and 0.36-0.42, respectively. CONCLUSIONS: GAD is associated with altered sympathovagal balance, characterized by attenuation in both resting vagal modulation and vagal reactivity, with an almost medium effect size (Cohen's d ≈ 0.4), regardless of medication use or comorbidity status.

Sex-specific pathways among tri-allelic serotonin transporter polymorphism, trait neuroticism and generalized anxiety disorder.

Background: Neuroticism personality trait is recognized as an important endophenotypic predictor of generalized anxiety disorder (GAD). Furthermore, endophenotype-based pathway approaches have recently been shown to have greater advantages for gene-finding strategies than traditional case-control studies. In the present study, in addition to conventional case-control methods, we used pathway analyses to test whether the tri-allelic serotonin transporter promoter polymorphism (combining 5-HTTLPR and rs25531) is associated with risk of GAD through its effects on trait neuroticism. Methods: We included 2236 Han Chinese adults in this study, including 736 patients with GAD and 1500 healthy participants. We genotyped the 5-HTTLPR and rs25531 polymorphisms using the polymerase chain reaction restriction fragment length polymorphism method. We used the Neuroticism scale of the Maudsley Personality Inventory (MPI) short version (MPI-Neuroticism) to measure participants' tendency toward neuroticism. Results: Using endophenotype-based path analyses, we found significant indirect effects of the tri-allelic genotype on risk of GAD, mediated by MPI-Neuroticism in both men and women. Compared to women carrying the S'S' genotype, women carrying the L' allele had higher levels of MPI-Neuroticism, which in turn were associated with higher risk of GAD. Men, however, showed the opposite pattern. Using traditional case-control comparisons, we observed that the effect of tri-allelic genotype on GAD was significant, but only in women. Limitations: Participants were restricted to Han Chinese, and we used only 1 questionnaire to assess neuroticism. Conclusion: These findings are the first to show that the triallelic 5-HTTLPR polymorphism is associated with elevated risk of GAD, and that this effect is mediated via increased trait neuroticism, a sex-dependent risk pathway.

Psychiatric Disorders After Traumatic Brain Injury: A Nationwide Population-Based Cohort Study and the Effects of Rehabilitation Therapies.

OBJECTIVE: To investigate the risk of psychiatric disorders after traumatic brain injury (TBI), and to clarify whether the post-TBI rehabilitation was associated with a lower risk of developing psychiatric disorders. DESIGN: A register-based, retrospective cohort design. SETTING: Using data from the National Health Insurance Research Database of Taiwan, we established an exposed cohort with TBI and a nonexposed group without TBI matched by age and year of diagnosis between 2000 and 2015. PARTICIPANTS: This study included 231,894 patients with TBI and 695,682 patients without TBI (N=927,576). INTERVENTIONS: Rehabilitation therapies in TBI patients. MAIN OUTCOME MEASURES: A multivariable Cox proportional hazards regression model was used to compare the risk of developing psychiatric disorders. RESULTS: The incidence rate of psychiatric disorders was higher in the TBI group than the control group. Compared with the control group, the risk of psychiatric disorders in the TBI group was twofold (hazard ratio [HR]=2.072; 95% confidence interval [95% CI], 1.955-2.189; P<.001). Among the participants with TBI, 49,270 (21.25%) had received rehabilitation therapy and had a lower risk of psychiatric disorders (HR=0.691; 95% CI, 0.679-0.703; P<.001). In the subgroup analysis, the medium- to high-level intensity rehabilitation therapy was associated with lower risks of psychiatric disorder (HR=0.712 and 0.568, respectively), but there was no significant finding in the low-intensity group. CONCLUSIONS: We found that TBI was associated with a high risk for developing psychiatric disorders, and that the post-TBI rehabilitation significantly reduced the risk of psychiatric disorders in a dose-dependent manner.

Effects of oxytocin on prosocial behavior and the associated profiles of oxytocinergic and corticotropin-releasing hormone receptors in a rodent model of posttraumatic stress disorder.

BACKGROUND: Traumatic experience may lead to various psychological sequelae including the unforgettable trauma-associated memory as seen in posttraumatic stress disorder (PTSD), with a mechanism of impaired fear extinction due to biological imbalance among hypothalamic-pituitary-adrenal (HPA) axis and fear circuit areas such as medial prefrontal cortex (mPFC), hippocampus, and amygdala. Recently the impaired sociability seen in PTSD patients received great attention and the involvement of oxytocin (OXT) mediation is worth being investigated. This study examined whether the trauma-altered prosocial behavior can be modulated by OXT manipulation and its relationship with corticotropin-releasing hormone (CRH) signaling. METHODS: Male rats previously exposed to a single prolonged stress (SPS) were evaluated for their performance in social choice test (SCT) and novel object recognition test (NORT) following the introduction of intranasal oxytocin (OXT) and OXT receptor antagonist atosiban (ASB). OXT receptors (OXTR) and CRH receptors (CRHR1, CRHR2) were quantified in both protein and mRNA levels in medial prefrontal cortex (mPFC), hippocampus, and amygdala. RESULTS: SPS reduced inclination of rats staying at the sociable place with performing less prosocial contacts. OXT can amend the deficit but this effect was blocked by ASB. Expression of OXTR became reduced following SPS in mPFC and amygdala, the latter exhibited higher therapeutic specificity to OXT. Expression of CRHR1 appeared more sensitive than CRHR2 to SPS, higher CRHR1 protein levels were found in mPFC and amygdala. CONCLUSION: Psychological trauma-impaired sociability is highly associated with OXT signaling pathway. Intranasal OXT restored both the SPS-impaired prosocial contacts and the SPS-reduced OXTR expressions in mPFC and amygdala. OXT may have therapeutic potential to treat PTSD patients with impaired social behaviors.

Mortality Risk of Atypical Antipsychotics for Behavioral and Psychological Symptoms of Dementia: A Meta-Analysis, Meta-Regression, and Trial Sequential Analysis of Randomized Controlled Trials.

BACKGROUND: Evidence suggests that atypical antipsychotics (AAPs) exert a short-term mortality risk in people with dementia. We assessed whether additional randomized clinical trials influence the current evidence and the potential effect modifiers. METHODS: Electronic databases were systematically searched for randomized controlled trials from their inception through March 2018. A random-effects model was used for analysis. Potential effect modifiers were examined through meta-regression. Trial sequential analysis was performed to quantify the statistical reliability of data in the cumulative meta-analysis with adjustment of significance levels for sparse data and repetitive testing on accumulating data. Certainty of evidence and risk of bias were also evaluated. RESULTS: We found that compared with placebos, AAPs may increase the risk of mortality (odds ratio [OR], 1.536; 95% confidence intervals [CIs], 1.028-2.296; P = 0.036, high certainty). In the subgroup analysis, the estimated ORs were the highest for olanzapine (1.919; P = 0.232), followed by those for quetiapine (1.663; P = 0.506), aripiprazole (1.649; P = 0.297), and risperidone (1.354; P = 0.277); however, the mortality risk presented by individual AAPs did not exhibit between-group differences. The meta-regression did not identify any effect modifiers, including the chlorpromazine equivalent dose, trial duration, and cognitive status. The trial sequential analysis revealed that future similar trials are unlikely to alter our findings. CONCLUSIONS: Atypical antipsychotics are associated with increased short-term mortality risk, although a disease-drug interaction may contribute to such risk in people with dementia. Patients with dementia may still benefit by AAPs after appropriate assessment of the disease severity as well as the dosage of AAPs, treatment duration, and monitoring of AAPs.

Pinworm infections associated with risk of psychiatric disorders-A nationwide cohort study in Taiwan: Pinworm infections and psychiatric disorders.

AIM: This study aimed to investigate the association between males with pinworm infections and the risk of developing psychiatric disorders. METHOD: A total of 2044 enrolled patients, with 511 pinworm subjects and 1533 unexposed subjects (1:3) matched for sex, age and index year, from Taiwan's Longitudinal Health Insurance Database (LHID) from 2000 to 2015, selected from the National Health Insurance Research Database (NHIRD). After adjusting for confounding factors, the Cox regression model was used to compare the risk of developing psychiatric disorders during the 15 years of follow-up. RESULTS: Of all the enrollees, 24 in the pinworm cohort and 18 in the unexposed cohort (343.10 vs 84.96 per 100,000 person-year) developed psychiatric disorders. The Cox regression model revealed that, after adjusting for sex, age, monthly income, urbanization level, geographic region, and comorbidities, the adjusted HR was 4.581 (95% CI: 2.214-9.480, p < .001, p < .001). Pinworm infections were associated with the increased risk in anxiety disorders, depressive disorders, and sleep disorders, respectively. CONCLUSION: Patients who suffered from pinworm infections have a higher risk of developing psychiatric disorders, and this finding should be considered as a timely reminder for the clinicians to provide much more attention for these patients because of their mental health issues.

Risk of sleep disorders in patients with decompression sickness: a nationwide, population-based study in Taiwan.

BACKGROUND: Decompression sickness (DCS) primarily manifests musculoskeletal pain, cutaneous manifestations, lymphatic symptoms, and neurological symptoms. DCS might affect the central nervous system and induce the stress in the patients, but few studies about the psychiatric morbidity after DCS have been conducted. This study aimed to investigate the association between DCS and the risk of developing psychiatric disorders. SUBJECTS AND METHODS: This study was a population-based, matched-cohort design. A total of 738 enrolled patients, with 123 study subjects who had suffered from DCS, and 615 controls matched for sex and age, from the Longitudinal Health Insurance Databank from 2000-2010 in Taiwan, and selected from the National Health Insurance Research Database. After adjusting for the confounding factors, Cox proportional hazards analysis was used to compare the risk of developing psychiatric disorders during the 10 years of follow-up period. RESULTS: Of the study subjects, 10 (8.13%) developed psychiatric disorders when compared to 35 (5.69%) in the control group. The study subjects were more likely to develop psychiatric disorders (crude hazard ratio [HR]: 2.79 (95% CI=1.37-5.69, P<0.01). After adjusting for sex, age, monthly income, urbanization level, geographic region, and comorbidities, the adjusted HR was 3.83 (95% CI=1.60-9.16, P<0.01). Sleep disorders was associated with DCS with the adjusted HR as 5.74 (95% CI=1.04-31.56, P<0.01). Hyperbaric oxygenation therapy was not associated with a lower risk of psychiatric disorders. CONCLUSIONS: Patients who suffered from DCS have a 3.8-fold risk of developing psychiatric disorders, and a 5.7-fold risk of sleep disorders. This finding is a reminder for the clinicians that a regular psychiatric follow-up might well be needed for these patients.

The Effects of Add-on Fronto-Temporal Transcranial Direct Current Stimulation (tDCS) on Auditory Verbal Hallucinations, Other Psychopathological Symptoms, and Insight in Schizophrenia: A Randomized, Double-Blind, Sham-Controlled Trial.

Background: The efficacy of fronto-temporal transcranial direct current stimulation in treating auditory verbal hallucinations and other psychopathological symptoms of schizophrenia patients has been examined in a small number of clinical trials with limited sample sizes, but the results are mixed. Fronto-temporal transcranial direct current stimulation has also been demonstrated to enhance patients' insight into their mental illness in an open-label pilot study. The current investigation aimed to investigate the therapeutic effects of fronto-temporal transcranial direct current stimulation on the severity of auditory verbal hallucinations, other schizophrenia symptoms, and insight in a large double blind, randomized, sham-controlled trial. Methods: Sixty patients with medication-refractory auditory verbal hallucinations were randomized over 2 conditions: transcranial direct current stimulation with 2-mA, twice-daily sessions for 5 consecutive days, with anodal stimulation to the left prefrontal cortex and cathodal stimulation to the left temporo-parietal junction, and sham treatment. Results: Fronto-temporal transcranial direct current stimulation failed to cause significant changes in the severity of auditory verbal hallucinations and other schizophrenia symptoms. The levels of insight into illness (effect size=0.511, P<.001) and positive symptoms (effect size=0.781, P<.001) were largely promoted by 5 days of transcranial direct current stimulation relative to sham treatment. The beneficial effects on the 2 insight dimensions remained 1 month after transcranial direct current stimulation. Conclusions: Fronto-temporal transcranial direct current stimulation is not more effective for auditory verbal hallucinations and other schizophrenia symptoms than sham treatment. But the results of transcranial direct current stimulation-associated improvement in awareness of illness and positive symptoms show promise and provide a new direction for future research into insight promotion interventions in schizophrenia.

Add-On Memantine Treatment for Bipolar II Disorder Comorbid with Alcohol Dependence: A 12-Week Follow-Up Study.

BACKGROUND: Bipolar disorder (BD), especially BD-II, is frequently comorbid with alcohol dependence. Because BD-II and alcohol dependence are neurodegenerative disorders, agents with anti-inflammatory and neurotrophic effects might provide effective therapy. We investigated whether add-on memantine to regular valproic acid treatment ameliorated clinical symptoms, reduced alcohol use, and cytokine levels, and increased plasma brain-derived neurotrophic factor (BDNF) in BD-II patients with comorbid alcohol dependence. METHODS: In a single-arm 12-week clinical trial, BD-II patients with comorbid alcohol dependence (n = 45) undergoing regular valproic acid treatments were given add-on memantine (5 mg/d). Symptom severity, alcohol use, cytokine (plasma tumor necrosis factor-α and C-reactive protein [CRP], transforming growth factor-ß1 [TGF-ß1], interleukin-8 [IL-8], IL-10), and plasma BDNF levels were regularly assessed. RESULTS: Mean within-group decreases in Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) scores, alcohol use, CRP, BDNF, and IL-8 levels were significantly different from baseline after 12 weeks of treatment. We found no significant correlation between alcohol use levels and changes in HDRS or YMRS scores. The correlation between reduced alcohol use and reduced TGF-ß1 level was significant (B = 0.003, p = 0.019). CONCLUSIONS: BD-II comorbid with alcohol dependence might benefit from add-on memantine treatment, which significantly reduced clinical severity, alcohol use, and plasma cytokine levels, and increased BDNF levels.

The impact of cognitive insight, self-stigma, and medication compliance on the quality of life in patients with schizophrenia.

Impaired quality of life (QoL) is a common and clinically relevant feature of schizophrenia. In the present study, we attempted to formulate a model of QoL in the chronic stage of schizophrenia by including key variables-namely cognitive insight, self-stigma, insight into treatment, and medication compliance-that were proposed as its significant predictors in previous studies. We employed structural equation modeling (SEM) to simultaneously test the associations between these variables. A total of 170 community-dwelling patients with schizophrenia participated in this study. Cognitive insight, self-stigma, insight into treatment, medication compliance, and QoL were assessed through self-reporting. Symptoms were rated by interviewers. The influences of cognitive insight, stigma, insight into treatment, and medication compliance on QoL were supported using SEM. Our findings indicated that cognitive insight had a significant, positive, and direct effect on both self-stigma and insight into treatment; in contrast, it had a negative and direct effect on medication compliance. Notably, no evidence indicated a direct effect of cognitive insight on QoL. Thus, individuals with high cognitive insight reported low QoL because of stigma, low medication compliance, and their increased insight into treatment. In contrast, cognitive insight might indirectly ameliorate QoL mediated by the effect of insight into treatment on medication compliance. The findings provide additional support of the links between cognitive and clinical insight, self-stigma, medication compliance, and QoL in those with schizophrenia and suggest the need for screening and intervention services appropriate for this high-risk population.

Risk of psychiatric disorders in irritable bowel syndrome-A nationwide, population-based, cohort study.

AIMS: This cohort study aimed to investigate the association between irritable bowel syndrome (IBS) and the risk of developing psychiatric disorders. METHODS: Utilizing the National Health Insurance Research Database (NHIRD) of Taiwan, IBS patients were identified and compared with age, sex, and index year-matched controls (1:3). RESULTS: Of the IBS subjects, 3934 in 22 356 (17.60%, or 1533.68 per 100 000 person-years) developed psychiatric disorders when compared with 6127 in 67 068 (9.14%, or 802 per 100 000 person-years) in the non-IBS control group. Fine and Gray's survival analysis revealed that the study subjects were more likely to develop psychiatric disorders. The crude hazard ratio (HR) is 3.767 (95% CI: 3.614-3.925, P < .001), and the adjusted HR is 3.598 (95% CI: 3.452-3.752, P < .001) in the risk of developing psychiatric disorders after being adjusted for age, sex, comorbidities, geographical area of residence, urbanisation level of residence, and monthly insurance premiums. The cohort study revealed that IBS subjects were associated with an increased risk of anxiety, depression, bipolar, and sleep disorders. CONCLUSIONS: This cohort study, using NHIRD, shows evidence support that patients with IBS have a 3.6-fold risk of developing psychiatric disorders. Other large or national datasets should be done to explore to underlying mechanisms.