Magnetization transfer ratio for assessing remyelination after transcranial ultrasound stimulation in the lysolecithin rat model of multiple sclerosis.

It has been shown that transcranial ultrasound stimulation (TUS) is capable of attenuating myelin loss and providing neuroprotection in animal models of brain disorders. In this study, we investigated the ability of TUS to promote remyelination in the lysolecithin (LPC)-induced local demyelination in the hippocampus. Demyelination was induced by the micro-injection of 1.5 µL LPC (1%) into the rat hippocampus and the treated group received daily TUS for 5 or 12 days. Magnetic resonance imaging techniques, including magnetization transfer ratio (MTR) and T2-weighted imaging, were used to longitudinally characterize the demyelination model. Furthermore, the therapeutic effects of TUS on LPC-induced demyelination were assessed by Luxol fast blue (LFB) staining. Our data revealed that reductions in MTR values observed during demyelination recover almost completely upon remyelination. The MTR values in demyelinated lesions were significantly higher in TUS-treated rats than in the LPC-only group after undergoing TUS. Form histological observation, TUS significantly reduced the size of demyelinated lesion 7 days after LPC administration. This study demonstrated that MTR was a sensitive and reproducible quantitative marker to assess remyelination process in vivo during TUS treatment. These findings might open new promising treatment strategies for demyelinating diseases such as multiple sclerosis.

Exposure to psychotropic medications and mortality in schizophrenia: a 5-year national cohort study.

BACKGROUND: Relatively few studies have explored the differential contributions of the accumulative dosage of psychotropic medications on mortality in patients with schizophrenia. METHODS: We aimed to explore the effects of the exposure dosage of psychotropic medications on mortality during a follow-up period of 5 years with a national cohort of individuals with schizophrenia in 2010. Causes of death were linked through Taiwan's National Mortality Registry. The mean defined daily dose of antipsychotics, antidepressants, mood stabilizers, and sedative-hypnotics, were calculated and survival analyses were conducted. RESULTS: A total of 102 964 individuals (54 151 men, 52.59%) with schizophrenia were included. Compared to patients with no exposure to antipsychotics, those with antipsychotic exposure had better survival outcomes, regardless of antipsychotic dosage. Antidepressant exposure, in low and moderate dosage, was associated with decreased all-cause mortality; exposure to mood stabilizers appeared to be associated with an increase in all-cause mortality. Although 89.7% of the patients had been prescribed sedative-hypnotics, exposure to sedative-hypnotics was associated with dose-related increased mortality risk [hazard ratio (HR) in low dose group: 1.16, 95% confidence interval (CI) 1.07-1.27; HR in moderate dose: 1.32, 95% CI 1.21-1.44; HR in high dose: 1.83, 95% CI 1.67-2.01)]. CONCLUSIONS: The results indicate that in the treatment of schizophrenia, antipsychotics and antidepressants are associated with lower mortality when using adequate dosages and mood stabilizers and sedative-hypnotics with higher mortality compared with no use. Furthermore, exposure to sedative-hypnotics is associated with a dose-related increased mortality risk which warrants clinical attention and further study.

Degree of exposure to psychotropic medications and mortality in people with bipolar disorder.

OBJECTIVES: To investigate the associations between psychotropic medication dosage and mortality in patients with bipolar disorder. METHODS: A nationwide cohort of individuals aged ≥15 years who had received a diagnosis of bipolar disorder in 2010 was identified from the Taiwanese national health-care database linked with the mortality registry and followed up for 5 years. The mean defined daily dose (DDD) of mood stabilizers, antipsychotics, antidepressants, and sedative-hypnotics was estimated, and survival analyses were conducted to assess the effects of degree of exposure to psychotropic medications on mortality. RESULTS: A total of 49,298 individuals (29,048 female individuals, 58.92%) with bipolar disorder were included. Compared with individuals without exposure to mood stabilizers, those prescribed mood stabilizers had a decreased overall mortality risk, regardless of exposure dosage. By contrast, compared with a reference group with no exposure to antipsychotics, individuals using antipsychotics had dose-dependent, increased mortality in both overall causes of deaths and deaths due to cardiovascular diseases, with hazard ratios of 1.13 (95% CI: 1.21-1.42) in the low-dose (<0.5 DDD) group, 1.69 (1.51-1.90) in the moderate-dose (0.5-1.5 DDD) group, and 2.08 (1.69-2.57) in the high-dose (>1.5 DDD) group for overall mortality. CONCLUSIONS: In sum, mood stabilizers were associated with decreased overall mortality in individuals with bipolar disorder, regardless of the dosage. However, the use of antipsychotics appeared to be associated with a dose-dependent increased mortality risk. Owing to study limitations, precise information on prior use of psychotropic medications, and patient's adherence to medication are not available. Potential adverse effects and benefits should be carefully considered when prescribing psychotropic medications for long-term use in patients with bipolar disorder.

Associations between mortality and exposure to psychotropic medication: A population-based cohort study for depressive disorders.

BACKGROUND: Use of antidepressants and antipsychotics to treat depressive disorders is becoming increasingly prevalent. METHODS: This study investigated how the use and cumulative dosage of these medications affect the mortality risk in a Taiwan's national cohort of individuals ages 15 years and older who were diagnosed with depressive disorders in 2010 and followed up for 5 years. An age- and gender-matched control group was identified. The mean defined daily doses of antidepressants and antipsychotics were calculated, and survival analyses were conducted to examine the effects of exposure dosage on overall mortality and mortality due to cardiovascular diseases, in comparison with the control sample. RESULTS: A total of 400,042 individuals (255,288 women; 63.8%) with depressive disorders were identified. A low-to-moderate dosage of antidepressants was associated with a decrease in cardiovascular disease-related mortality risks compared to no exposure for those with depressive disorders. By contrast, a dose-related increase was found when using antipsychotics, with a 1.6-, 2.4- and 2.9-fold risk in the low, moderate and high exposure groups, respectively, for overall mortality, and a 1.2-, 2.4- and 3.5-fold risk in the low, moderate and high exposure groups, respectively, for cardiovascular disease-related mortality, relative to the control sample. CONCLUSION: For individuals with depression, use of low-to-moderate dosage antidepressants was associated with decreased mortality. However, use of antipsychotics was found to be associated with a dose-related increase in overall and cardiovascular disease-related mortality risks. Adverse health outcomes should be also considered when prescribing psychotropic medications to patients with depressive disorders.

Nicotine Replacement Therapy and Healthy Lifestyle Psychoeducation for Smoking Reduction in Acute Psychiatric Inpatients: A Cluster-Randomized Parallel Study.

BACKGROUND: Effectiveness of nicotine replacement therapies in acute psychiatric inpatient settings remains under-researched. The aim of this study was to compare effectiveness and acceptability of 3 different forms of nicotine replacement therapy in achieving smoking reduction among acute psychiatric inpatients. METHODS: This cluster-randomized, parallel study compared effectiveness and acceptability of nicotine inhalers, nicotine gum, and nicotine patches for smoking reduction in the acute psychiatric inpatient setting. The primary outcome was the exhaled breath carbon monoxide (CO) level change from baseline at weeks 4 and 8. Secondary outcomes included changes in nicotine withdrawal symptoms and psychiatric symptom severity. RESULTS: Three hundred ten inpatients on the acute care wards were randomly assigned to nicotine inhalers (n = 184), gum (n = 71), and patches (n = 55). Only the nicotine inhaler group showed statistically significant reduction in CO level from baseline at both weeks 4 and 8 (P < 0.001 and P = 0.032, respectively). The nicotine inhaler and the patch group showed significant decrease in nicotine withdrawal symptoms from baseline at both weeks 4 and 8. Meanwhile, the nicotine inhaler and the gum group showed significant decrease in psychiatric symptom severity from baseline at both weeks 4 and 8. Post hoc comparisons revealed that the inhaler group had a greater decrease in psychiatric symptom severity compared with the patch group. CONCLUSIONS: Nicotine inhalers may be an effective choice for smoking reduction in acute psychiatric inpatient settings given its significant effects on CO level, withdrawal symptoms, and psychiatric symptom severity, particularly during the first 4 weeks of treatment.

The influence of friendship on migraine in young adolescents: A social network analysis.

OBJECTIVE: The current study explored whether the chances of having migraine are influenced by a youth's friendship with a migraineur. METHODS: The study was centered on a community-based non-referral cohort of eighth graders from two middle schools in Taiwan. Among the 642 recruited adolescent students, 610 (95%) (mean age 14.1 years, male ratio 51.2%) nominated three good friends and completed a validated headache questionnaire for migraine diagnosis at the follow-up survey 1 year later. To explore social influences on incident migraine, we used longitudinal statistical models to examine whether the development of migraine in one adolescent during the 1-year observational period was associated with that in his/her friends. RESULTS: Overall, 1700 social ties were established in the social network based on the reported lists of good friends. Randomization test for the homophily effect demonstrated that the students with migraine tended to cluster together in the social network even when those with incident migraine were also considered (p = 0.003). Besides, when friendship choices were mutual, the relative risk of an adolescent becoming a migraineur was 3.26 (95% CI: 1.25-8.47, p = 0.015) if his/her friend became a migraineur (induction) during the 1-year observational period. CONCLUSION: To the best of our knowledge, this is the first study to demonstrate that migraine may spread through social networks in young adolescents. Both homophily and induction effects are possibly contributory.

Quetiapine ameliorates collagen-induced arthritis in mice via the suppression of the AKT and ERK signaling pathways.

OBJECTIVE AND DESIGN: To investigate the amelioration effects of quetiapine on rheumatoid arthritis with RAW 264.7 macrophage and collagen-induced arthritis (CIA) DBA/1J mouse model. SUBJECTS: RAW 264.7 macrophage and DBA/1J mice. TREATMENT: Lipopolysaccharide and collagen. METHODS: RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS) followed by quetiapine treatments were investigated. Activations of CD80 and CD86 were analyzed by flow cytometry. Pro-inflammatory cytokines such as IL-6, TNF-α and IL-1ß were analyzed by ELISA. Proteins involved in signaling pathways related to the formation of rheumatoid arthritis were assayed by Western blotting. Therapeutic efficacy of quetiapine in CIA mouse model was also assayed. 18F-FDG/micro-PET was used to monitor the inflammation status in the joints, and the severity of bone erosion was evaluated with micro-CT and H&E staining. RESULTS: The inhibition of pro-inflammatory cytokines by quetiapine was found through the ERK and AKT phosphorylation and subsequent NF-κB and CREB signaling pathways. Pro-inflammatory cytokines such as IL-17, IL-6 and IL-1ß were decreased, while immunosuppressive factors such as TGF-ß and IL-10 were increased in CIA mice treated with quetiapine. Notably, no uptake of 18F-FDG and bone erosion was found with micro-PET images on days 32 and 43 in the quetiapine-treated and normal control groups. However, significant uptake of 18F-FDG could be observed in the CIA group during the same time course. Similar results were further verified with ex vivo autoradiography. CONCLUSION: Taken together, these results suggest that quetiapine is a potential anti-inflammatory drug, and may be used as an adjuvant for the treatment of rheumatoid arthritis.

Time to Discontinuation of Second-Generation Antipsychotics Versus Haloperidol and Sulpiride in People With Schizophrenia: A Naturalistic, Comparative Study.

PURPOSE: A retrospective study was conducted to evaluate the time to discontinuation (TTD) of the first- (FGAs) and second-generation antipsychotics (SGAs). METHODS: In total, 918 treatment episodes of patients with schizophrenia, initiated on one of the investigated drugs on an outpatient basis during 2004-2006, were entered into the study. The primary outcome was the duration of the investigated treatment episode. Discontinuation was defined when either patients were admitted or the investigated drug had been stopped for more than 28 days. We used the Cox proportional hazard model to compare hazards of discontinuations among 8 SGAs versus 2 FGAs (haloperidol and sulpiride). The follow-up period was up to 18 months. RESULTS: During the follow-up period, clozapine had the highest rate of continuous treatment in the primary analysis: clozapine, 40.6%; olanzapine, 23.4%; aripiprazole, 22.9%; amisulpride, 21.9%; zotepine, 21.3%; sulpiride, 17.0%; risperidone, 12.8%; quetiapine, 12.5%; haloperidol, 10.6%; and ziprasidone, 10.4%. Compared with haloperidol, 5 SGAs had significantly longer TTD (adjusted hazard ratios and 95% confidence intervals): clozapine (0.403, 0.267-0.607), olanzapine (0.611, 0.439-0.849), aripiprazole (0.570, 0.407-0.795), amisulpride (0.680, 0.487-0.947), and zotepine (0.687, 0.497-0.948), but only clozapine had significantly longer TTD compared with sulpiride (0.519, 0.342-0.786). The sensitivity analysis showed similar results. IMPLICATIONS/CONCLUSIONS: The current findings suggested that SGAs or FGAs are not homogeneous groups. Clozapine has the highest rate of continuous treatment among SGAs, and haloperidol is not the representative drug for all FGAs. Furthermore, antipsychotics dropout rate is high in naturalistic situation. A good service model needs to be constructed to enhance antipsychotic treatment adherence of people with schizophrenia.

Longitudinal risk factors for suicidal thoughts in depressed and non-depressed young adolescents.

OBJECTIVE: Evidence regarding the role of risk factors in the longitudinal course of suicidal ideation among young adolescents is lacking. We aimed to assess the effects of a range of risk factors, including obesity, academic performance, child-parent relationship, physical maltreatment, and depressive symptoms, on the development of suicidal ideation in young adolescents. METHODS: A school cohort of seventh and eighth graders was followed for 1 year and differences in the risk factors distributions were examined between depressed and non-depressed adolescents. We further examined risk factors for newly developed suicidal ideation and persistent suicidal ideation in the groups of adolescents based on the presence of suicidal ideation at baseline. RESULTS: A total of 1710 young adolescents were recruited, among whom 8.2% were categorised as having clinically significant depression. For depressed adolescents, being obese was associated with a three-fold increased risk of having suicidal ideation. For non-depressed adolescents, physical maltreatment, a feeling of not being cared about and sub-threshold depressive symptoms were the risk factors. The latter two remained robust in predicting newly developed suicidal ideation. CONCLUSION: The current study may shed light on the differential strategies to address suicidal thoughts in depressed and non-depressed adolescents. We emphasise the importance of recognition and management of sub-threshold depressive symptoms and the relevance of obesity, physical maltreatment and a feeling of not being cared about to suicide prevention programmes in early adolescence.

Carotid blowout and cerebral gas embolism related to bidirectional carotid-esophageal fistula: a serious complication of esophageal cancer under radiotherapy.

Carotid-esophageal fistula (CEF) could be a serious complication of esophageal cancer in a patient receiving radiotherapy. We reported a 47-year-old male patient with advanced cervical esophageal cancer under radiotherapy who developed CEF with the presentations of unstable vital signs and disturbances of consciousness. Carotid-esophageal fistula-associated life-threatening conditions of carotid blowout syndrome and cerebral gas embolism were diagnosed after presentation. Subsequently, intramural dissection of esophageal and gastric walls, profound hemoperitoneum, and hypovolemic shock occurred. When a patient who had an underlying cervical esophageal cancer treated by radiotherapy develops unstable vital signs and neurological symptoms, CEF should be kept in mind in the differential diagnoses. Physicians must be alert of the associated complications of carotid blowout syndrome and cerebral gas embolism and perform timely management including decompression, fluid resuscitation, and aggressive endovascular procedure when indicated.

Hyperdense Artery Sign, Clot Characteristics, and Response to Intravenous Thrombolysis in Han Chinese People with Acute Large Arterial Infarction.

BACKGROUND: Whether the presence of hyperdense artery sign (HAS) correlates with clot characteristics and response to intravenous thrombotic therapy (IVT) remains to be determined. Given that the existent literature was mainly from the Western nations, the current study aimed to examine the relationships among HAS, clot characteristics, and outcome of IVT in a Han Chinese sample in Taiwan. The specific objectives are (1) to correlate HAS with clot characteristics and (2) to explore relationships between HAS and effectiveness/complication of IVT. METHODS: We enrolled 75 patients treated with IVT following acute large arterial infarctions. All patients had a baseline brain computed tomography and a follow-up image at 24 hours after thrombolysis. Correlations were explored between HAS and clot characteristics. Multivariable logistic regressions were employed to examine the relationships between HAS and response to IVT at 24 hours, including early improvement and all forms of intracerebral hemorrhage (ICH). RESULTS: In this Han Chinese sample in Taiwan, 50.7% of the patients had HAS and 64% had early improvements following IVT. Those with HAS tended to have clots lodging at main trunks of cerebral arteries but no significant associations were found between HAS and stroke etiology. In multivariable logistic regressions, HAS predicted neither early improvement nor ICH complication. CONCLUSIONS: Instead of clot etiology, we found that it might be clot location that correlated with HAS. HAS was not associated with early improvement or ICH complication after IVT in this Han Chinese sample. We also showed that some other patient characteristics were likely to influence outcomes of IVT, which warrant clinical attention.

Treatment effects of combining social skill training and parent training in Taiwanese children with attention deficit hyperactivity disorder.

BACKGROUND/PURPOSE: Children with attention-deficit/hyperactivity disorder (ADHD) often have problems in social interactions. We investigated the social and behavioral effects of providing both social skill training and parent training to school-aged children with ADHD in Taiwan. METHODS: Seven consecutive 8-week behavioral-based social skill training (SST) group sessions were held for 48 children with ADHD; parallel 8-week parent group sessions were provided simultaneously. Fifty-five children with ADHD were recruited as a control group. All children took medication as prescribed by their doctors. The effects were assessed using the teacher and parent version of the Chinese version of Swanson, Nolan, and Pelham, version IV scale (SNAP-IV), the Chinese version of the Child Behavior Check List (CBCL-C), child and teacher version of the modified Social Skill Rating System (SSRS-C and SSRS-T), at baseline, post-treatment, and 4 months from baseline. The doses of methylphenidate and drug compliance were controlled during the analysis. RESULTS: The mixed-effects model demonstrated the main effect of group sessions on the Oppositional subscale of SNAP-P, the Anxious/Depressed subscale of CBCL-C, the Self Control subscale of SSRS-C, and the Active Participation subscale of SSRS-T, all in favor of the experimental group. However, the improvement on the Oppositional subscale of SNAP-P and the Self Control subscale of SSRS-C were noted only between baseline and post-treatment period and were not sustained at the end of the follow-up period. CONCLUSION: Our study demonstrated that children with ADHD could benefit from this low intensity psychosocial program, although some improvements were not maintained at follow-up assessment.

Antipsychotic discontinuation in patients with dementia: a systematic review and meta-analysis of published randomized controlled studies.

BACKGROUND: There is a lack of clarity in the literature on the impact of antipsychotic discontinuation in dementia. METHOD: We conducted a systematic review and meta-analysis of published randomized controlled studies comparing the effects of antipsychotic discontinuation versus continuation in dementia. MEDLINE, EMBASE, PsycInfo, Cochrane Library and CINAHL were searched. Severity change of behavioral and psychological symptoms of dementia (BPSD) was the primary outcome. RESULTS: Ten studies were included in the systematic review and 9 studies in the meta-analysis. The results showed that the antipsychotic discontinuation group had no statistically significant difference in BPSD severity change compared to the continuation group (n = 214, standardized mean difference: 0.19, 95% CI: -0.20 to 0.58). Secondary outcome analyses revealed that the discontinuation group included a statistically significantly higher proportion of subjects whose BPSD severity worsened (n = 366, risk ratio: 1.78, 95% CI: 1.31-2.41). Although not statistically significant, the discontinuation group appeared to have higher early study termination rates and a lower mortality during follow-up. CONCLUSIONS: This meta-analysis showed that antipsychotic discontinuation resulted in no statistically significant difference in BPSD severity change, early study terminations and mortality. However, a statistically significantly higher proportion of subjects with BPSD worsened in this group compared to the continuation group. Further studies are needed to explore the effects of antipsychotic discontinuation on BPSD. © 2013 S. Karger AG, Basel.

Psychotropic medications and mortality from cardiovascular disease and suicide for individuals with depression in Taiwan.

BACKGROUND: Polypharmacy for treatment of depression has been increasing in Taiwan. METHODS: Individuals having depressive disorders were identified in a national database for healthcare services and followed up for 5 years. The mean dosage of antidepressants, antipsychotics, mood stabilizers, and sedative-hypnotics was calculated; the associations between the exposure dosage to different psychotropic medications and patients' overall death and death due to cardiovascular diseases (CVD) and suicide were examined. RESULTS: A total of 400,042 individuals with depressive disorders (63.8% women) were identified. Compared with those with no exposure to antidepressants, patients prescribed antidepressants had decreased mortality. Use of antipsychotics had a dose-related increase in overall mortality risk compared to no exposure group. Contrarily, depressed patients taking sedative-hypnotics had decreased overall and CVD mortality compared to no exposure group, with the most prominent decrease in CVD mortality of up to 54.9% for those in the moderate exposure group (hazard ratio: 0.451, 95% confidence interval: 0.405-0.503). A moderate or high dose of antidepressants or sedative-hypnotics was shown to be associated with a significantly increased mortality for suicide compared to those with no exposure. CONCLUSIONS: Antidepressant and sedative-hypnotic use was associated with decreased all-cause and CVD-related mortality and use of antipsychotics was associated with a dose-related increase in mortality risk. Future studies are needed to further clarify the involved mechanisms and benefits and risks should be carefully weighed when prescribing psychotropic medications in patients with depressive disorders.

Medication Dosage Impact on Mortality in Old-Age Individuals with Schizophrenia: A National Cohort Study.

As the prevalence of old-age individuals with schizophrenia (OAS) increases in a society undergoing demographic aging, the exploration of medication choices becomes increasingly crucial. Due to the current scarcity of literature on OAS, this study seeks to examine how the utilization and cumulative dosages of psychotropic medications influence both overall and cause-specific mortality risks within this population. A national cohort of 6433 individuals diagnosed with OAS was followed up for 5 years. This study involved comparing the mortality rates associated with low, moderate, and high dosages of antipsychotics, antidepressants, mood stabilizers, and sedative/hypnotic drugs against the 'no exposure' category, based on individual dosages. Cox regression was employed for survival analyses to compare overall mortality and specific-cause mortality across various dosage groups. The exposure variable examined was the dosage of a specific psychotropic medication. Covariates were adjusted accordingly. The analysis revealed that patients on low/moderate antipsychotic doses had improved survival compared to non-exposed individuals. Moderate antipsychotic use corresponded to reduced cardiovascular disease mortality risk. Similarly, those exposed to antidepressants had enhanced survival in low and moderate doses. Sedative-hypnotic exposure was linked to decreased mortality risk in low doses. This study observed that low/moderate antipsychotic doses in older adults with schizophrenia were associated with decreased all-cause mortality, emphasizing the significance of precise medication selection and dosing. It underscores the need for vigilant polypharmacy management and tailored medication strategies in addressing the complexities of treating OAS.

Medication-Seeking Behaviors and Correlated Characteristics of Zolpidem Users in Taiwan-A Shared Patient Network Analysis.

Increasing insomnia signals a public health problem, alongside rising zolpidem use. This study investigates the factors behind the disproportionate rise in zolpidem prescriptions in Taiwan. It aims to identify the determinants of high-dose zolpidem users in Taiwan's Yilan County and employ an innovative approach to outline their medication-seeking patterns, using Taiwan's healthcare database. The associations between sociodemographic and clinical factors and low-dose and high-dose users were analyzed using multiple logistic regression. Social network analysis was employed to explore medication-seeking behavior among these user groups across different healthcare institutions. Of our 5290 participants, 22.82% are high-dose users. This study found that males face a 1.33-fold higher risk and that having chronic diseases is a major risk factor, contributing to a more than four-times higher risk (adjusted OR = 4.27, 95% CI 1.55-11.70) of being a high-dose user of zolpidem. A social network analysis showed a higher density (0.52) for high-dose users, revealing their frequent visits, for zolpidem, to different healthcare institutions. Psychiatrists have a central role in both low-dose and high-dose user networks, with a greater influence on low-dose users (64.4) than high-dose users (32.2). In sum, patients seeking high doses of zolpidem are driven by personal factors. Future efforts should include regulated dispensing, public health education, and specialized training for healthcare professionals on drug addiction.

Focused Ultrasound Stimulates the Prefrontal Cortex and Prevents MK-801-Induced Psychiatric Symptoms of Schizophrenia in Rats.

BACKGROUND AND HYPOTHESIS: Treatment of schizophrenia remains a major challenge. Recent studies have focused on glutamatergic signaling hypoactivity through N-methyl-D-aspartate (NMDA) receptors. Low-intensity pulsed ultrasound (LIPUS) improves behavioral deficits and ameliorates neuropathology in dizocilpine (MK-801)-treated rats. The aim of this study was to investigate the efficacy of LIPUS against psychiatric symptoms and anxiety-like behaviors. STUDY DESIGN: Rats assigned to 4 groups were pretreated with or without LIPUS for 5 days. The open field and prepulse inhibition tests were performed after saline or MK-801 (0.3 mg/kg) administration. Then, the neuroprotective effects of LIPUS on the MK-801-treated rats were evaluated using western blotting and immunohistochemical staining. STUDY RESULTS: LIPUS stimulation of the prefrontal cortex (PFC) prevented deficits in locomotor activity and sensorimotor gating and improved anxiety-like behavior. MK-801 downregulated the expression of NR1, the NMDA receptor, in rat medial PFC (mPFC). NR1 expression was significantly higher in animals receiving LIPUS pretreatment compared to those receiving only MK-801. In contrast, a significant increase in c-Fos-positive cells in the mPFC and ventral tegmental area was observed in the MK-801-treated rats compared to those receiving only saline; this change was suppressed by pretreatment with LIPUS. CONCLUSIONS: This study provides new evidence for the role of LIPUS stimulation in regulating the NMDA receptor and modulating c-Fos activity, which makes it a potentially valuable antipsychotic treatment for schizophrenia.

Socioeconomic disadvantage, mental disorders and risk of 12-month suicide ideation and attempt in the National Comorbidity Survey Replication (NCS-R) in US.

PURPOSE: We aim to explore the distinctive interrelationships between family income and mental disorders on suicidality in recent 12 months. METHODS: A stratified random subsample of adults in a household survey in US, National Comorbidity Survey Replication, was used for analyses. The ratio of family income to poverty threshold (RoFIPT) per capita was the primary predictor of interest to 12-month occurrence of suicide ideation and attempt. Effect modification by mental disorders was further explored. RESULTS: A total of 4,724 subjects were analyzed. Inverse associations were found with RoFIPT for both suicidal outcomes after confounding control. Furthermore, effect modification was revealed that RoFIPT was more strongly associated with suicide ideation for those with mental disorders (OR 0.87; 95 % CI 0.79, 0.95). CONCLUSIONS: An inverse gradient of RoFIPT was shown with suicide ideation and attempt. Moreover, having mental disorders was found to be an effect modifier for the relationships between family income and suicidality.

Correlates of anxiety and depressive symptoms in inpatients with COVID-19 in Taiwan.

Objectives: Inpatients with COVID-19 may experience high levels of anxiety and depressive symptoms during the pandemic. No prior study has examined these symptoms with COVID-19 inpatients in Taiwan. Using data from a tertiary hospital in Northern Taiwan, we investigated anxiety and depressive symptoms and the associated sociodemographic or clinical characteristics in these patients. Methods: Data of anxiety and depressive symptoms by the Hospital Anxiety and Depression Scale (HADS) as well as the sociodemographic and clinical correlates were retrospectively retrieved and analyzed for COVID-19 patients admitted to Far Eastern Memorial Hospital from June 4 to June 28, 2021. Results: In total, 152 patients with COVID-19 were included. Among all the COVID-19 inpatients, 9.9 % (n = 15) had an HADS anxiety score of ≥8 and 7.2 % (n = 11) had an HADS depression score of ≥8. COVID-19 inpatients with HADS anxiety score ≥8 or HADS depression score ≥8 were found to have a longer length of hospital stay compared to the respective comparison group. The female patients, patients aged >55 years, and patients hospitalized for >15 days had significantly higher anxiety scores than did the corresponding comparison groups. Conclusion: COVID-19 inpatients with either anxiety or depression were associated with longer length of hospital stay. Age, sex, and hospitalization length were found to be associated with anxiety symptoms in inpatients with COVID-19. Future studies are warranted to elucidate differential mechanisms potentially related to anxiety and depressive symptoms in patients with COVID-19.

Antipsychotics and Mortality in Adult and Geriatric Patients with Schizophrenia.

Patients with schizophrenia have a high mortality risk, and the role of antipsychotic medications remains inconclusive. In an aging society, older patients with schizophrenia warrant increased attention. This study investigated the association of antipsychotic medication dosages with mortality in patients with schizophrenia by using data from Taiwan's National Health Insurance Research Database from 2010 to 2014. This study included 102,964 patients with schizophrenia and a subgroup of 6433 older patients in addition to an age- and sex-matched control group. The findings revealed that among patients with schizophrenia, the no antipsychotic exposure group had the highest mortality risk (3.61- and 3.37-fold higher risk for overall and cardiovascular mortality, respectively) in the age- and sex-adjusted model, followed by the high, low, and moderate exposure groups. A similar pattern was observed in the older patients with schizophrenia. High exposure to antipsychotics was associated with the highest risks of overall and cardiovascular mortality (3.01- and 2.95-fold higher risk, respectively). In conclusion, the use of antipsychotics can be beneficial for patients with schizophrenia with recommended exposure levels being low to moderate. In older patients, high antipsychotic exposure was associated with the highest mortality risk, indicating that clinicians should be cautious when administering antipsychotic medications to such patients.