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Bipolar disorder is a chronic mental disorder related to cognitive deficits. Low serum vitamin D levels are significantly associated with compromised cognition in neuropsychiatric disorders. Although patients with bipolar disorder frequently exhibit hypovitaminosis D, the association between vitamin D and cognition in bipolar disorder, and their neuroaxonal integrity, is unclear.
To investigate the interaction effects between vitamin D and neurofilament light chain (NfL) levels on cognitive domains in bipolar disorder.
Serum vitamin D and NfL levels were determined in 100 euthymic patients with bipolar disorder in a cross-sectional study. Cognitive function was measured with the Brief Assessment of Cognition in Affective Disorders. We stratified by age groups and used general linear models to identify associations between vitamin D and NfL levels and their interaction effects on cognitive domains.
The mean vitamin D and NfL levels were 16.46 ng/nL and 11.10 pg/mL, respectively; 72% of patients were vitamin D deficient. In the older group, more frequent hospital admissions and lower physical activity were identified in the group with versus without vitamin D deficiency. The age-modified interaction effect of vitamin D and NfL was associated with composite neurocognitive scores and verbal fluency in both age groups, and with processing speed domain in the younger group.
We observed a high vitamin D deficiency prevalence in bipolar disorder. We identified the interaction of vitamin D and NfL on cognitive domains, and the effect was modified by age. Longitudinal or randomised controlled studies enrolling patients with various illness durations and mood statuses are required to validate our findings.
The effects of non-invasive, non-convulsive electrical neuromodulation (NINCEN) on depression, anxiety and sleep disturbance are inconsistent in different studies. Previous meta-analyses on transcranial direct current stimulation (tDCS) and cerebral electrotherapy stimulation (CES) suggested that these methods are effective on depression. However, not all types of NINECN were included; results on anxiety and sleep disturbance were lacking and the influence of different populations and treatment parameters was not completely analyzed. We searched PubMed, Embase, PsycInfo, PsycArticles and CINAHL before March 2021 and included published randomized clinical trials of all types of NINCEN for symptoms of depression, anxiety and sleep in clinical and non-clinical populations. Data were pooled using a random-effects model. The main outcome was change in the severity of depressive symptoms after NINCEN treatment. A total of 58 studies on NINCEN were included in the meta-analysis. Active tDCS showed a significant effect on depressive symptoms (Hedges' g = 0.544), anxiety (Hedges' g = 0.667) and response rate (odds ratio = 1.9594) compared to sham control. CES also had a significant effect on depression (Hedges' g = 0.654) and anxiety (Hedges' g = 0.711). For all types of NINCEN, active stimulation was significantly effective on depression, anxiety, sleep efficiency, sleep latency, total sleep time, etc. Our results showed that tDCS has significant effects on both depression and anxiety and that these effects are robust for different populations and treatment parameters. The rational expectation of the tDCS effect is ‘response’ rather than ‘remission’. CES also is effective for depression and anxiety, especially in patients with disorders of low severity.
During the first postnatal week in rodents, cholinergic retinal waves initiate in starburst amacrine cells (SACs), propagating to retinal ganglion cells (RGCs) and visual centers, essential for visual circuit refinement. By modulating exocytosis in SACs, dynamic changes in the protein kinase A (PKA) activity can regulate the spatiotemporal patterns of cholinergic waves. Previously, cysteine string protein-α (CSPα) is found to interact with the core exocytotic machinery by PKA-mediated phosphorylation at serine 10 (S10). However, whether PKA-mediated CSPα phosphorylation may regulate cholinergic waves via SACs remains unknown. Here, we examined how CSPα phosphorylation in SACs regulates cholinergic waves. First, we identified that CSPα1 is the major isoform in developing rat SACs and the inner plexiform layer during the first postnatal week. Using SAC-specific expression, we found that the CSPα1-PKA-phosphodeficient mutant (CSP-S10A) decreased wave frequency, but did not alter the wave spatial correlation compared to control, wild-type CSPα1 (CSP-WT), or two PKA-phosphomimetic mutants (CSP-S10D and CSP-S10E). These suggest that CSPα-S10 phosphodeficiency in SACs dampens the frequency of cholinergic waves. Moreover, the level of phospho-PKA substrates was significantly reduced in SACs overexpressing CSP-S10A compared to control or CSP-WT, suggesting that the dampened wave frequency is correlated with the decreased PKA activity. Further, compared to control or CSP-WT, CSP-S10A in SACs reduced the periodicity of wave-associated postsynaptic currents (PSCs) in neighboring RGCs, suggesting that these RGCs received the weakened synaptic inputs from SACs overexpressing CSP-S10A. Finally, CSP-S10A in SACs decreased the PSC amplitude and the slope to peak PSC compared to control or CSP-WT, suggesting that CSPα-S10 phosphodeficiency may dampen the speed of the SAC-RGC transmission. Thus, via PKA-mediated phosphorylation, CSPα in SACs may facilitate the SAC-RGC transmission, contributing to the robust frequency of cholinergic waves.
To investigate potential risk factors for mild behavioral impairment (MBI) among non-demented geriatrics.
Population-based, cross-sectional survey.
Taiwan Alzheimer Disease Association (TADA) Database.
Participants were selected by multistage random sampling of all Taiwan counties. They received in-person interviews between December 2011 and March 2013.
Demographic data, lifestyle and habits, medical comorbidities, cognitive status measured by the Taiwanese Mini-Mental Status Examination (TMSE) and presence of MCI of the participants were collected. Subjects were distributed to the MBI and non-MBI groups. These factors had been evaluated for their effects on MBI in the univariate and multivariable logistic regression models.
In total, 6,196 non-demented participants aged 65 years or older, including 409 MBI and 5,787 non-MBI participants, were recruited. After adjustment for age, sex, education, body mass index, lifestyle and habits, medical comorbidities, and MCI, good sleep was associated with lower risk of MBI (OR 0.09, 95% CI 0.07 – 0.12). Low body weight (OR 2.01, 95% CI 1.21–3.33), low-to-medium education (OR 1.40, 95%CI 1.06–1.85; OR 2.32, 95% CI 1.67–3.21), medical comorbidities of hypertension (OR 1.56, 95% CI 1.25–1.95), hyperlipidemia (OR 1.29, 95% CI 1.00–1.67), cancer (OR 2.05, 95% CI 1.37–3.06) were significantly associated with increased MBI risk. MCI neither increased nor decreased risk of MBI (OR 1.00, 95% CI 0.76–1.32).
Good sleep was associated with lower MBI risk. Underweight, lower education, medical comorbidities of cancer, hypertension, hyperlipidemia were predictive of MBI.
Supported by (1) medical research grants CMRPG3C0041/42 from Chang Gung Memorial Hospital and NRRPG2H0031 from Ministry of Science and Technology, Taiwan to Chemin Lin (2) NMRPG3G6031/32 from Ministry of Science and Technology, Taiwan to Shwu-Hua, Lee (3) the KKHo International Charitable Foundation to Tatia Lee.
Suicide rate tends to peak in old age, and major depression is the most salient risk factor for late-life suicide. However, few studies have focused on the neuroscientific facet of suicide in the context of late-life depression (LLD).
We recruited 114 participants of LLD (28 with history of suicide attempt and 86 without) and 47 elderly controls. They received MRI scanning and behavioral assessment. White matter hyperintensity (WMH) was quantified by an automated segmentation algorithm and graph theoretical analysis was applied to resting-state fMRI. We used ANCOVA to compare group difference in WMH loading and multivariate generalized linear model to compare global and local topological parameters in fMRI signals, controlling for demographics. Partial correlation was conducted between imaging parameters and behavioral data in group of suicide attempters.
We found significant higher WMH in suicide attempters than those of LLD without suicide attempts and elderly controls (F =7.091; p = 0.001). Suicide attempters also had increased betweenness centrality (BC) in right superior occipital gyrus (SOG) (Bonferroni corrected), right precuneus (False positive corrected) and right superior temporal gyrus (uncorrected) and decreased BC in left hippocampus (uncorrected). In suicide attempters, higher BC in right SOG correlated with higher WMH, higher depression severity, higher illness awareness and insight, and lower cognitive function (digit backward), while higher BC in right precuneus correlated with higher decrease awareness and insight and higher cognitive function (digit backward).
Resonating with the vascular hypothesis in LLD, higher WMH was found in those having history of suicide attempts. However, the re-organized brain topology changes are related with divergent cognitive function and convergent heightened disease insight.
Rice (Oryza sativa L.) is the primary staple crop in Taiwan, and it can be grown twice a year. The prevalent subspecies grown in Taiwan is Japonica, and a transplanting system is used for rice production. Although the transplanting system is known for efficient weed control at the seedling stage, weedy red rice (WRR, O. sativa f. spontanea) infestation is progressively being reported. Fieldwork and previous studies have suggested that WRR infestation in Taiwan is probably related to growers’ operating practices and their perception of WRR. However, no data are available for a detailed investigation. The present study aimed to collect data on rice growers’ backgrounds, farming practices, and perceptions of WRR to quantify and characterize the patterns of farming operations for rice growers in Taiwan and to investigate factors contributing to WRR infestation. We collected 408 questionnaires completed by rice growers from 17 counties covering all rice production regions in Taiwan. The growers’ median age was 51 to 60 yr, and 75% of respondents had paddies from 0.25 to 2.75 ha in size, which corresponded with nationwide data for farmers’ backgrounds. In general, growers applied similar farming practices for both cropping seasons. Most respondents did not notice WRR infestation or consider it to be a problem: only 9.8% noticed a moderate to severe infestation of WRR in their fields. The major perceived causes of WRR infestation was seed impurity (55.1%) or cultivar degeneration (18.6%). Correlation analysis and farming patterns estimated with a nonnegative matrix factorization algorithm showed that WRR contamination rate was due to the use of dry or wet tillage. The present study provides the first quantitative and qualitative evidence of rice production practices and growers’ perceptions of WRR infestation in Taiwan.
Family coaggregation of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia have been presented in previous studies. The shared genetic and environmental factors among psychiatric disorders remain elusive.
This nationwide population-based study examined familial coaggregation of major psychiatric disorders in first-degree relatives (FDRs) of individuals with ASD. Taiwan's National Health Insurance Research Database was used to identify 26 667 individuals with ASD and 67 998 FDRs of individuals with ASD. The cohort was matched in 1:4 ratio to 271 992 controls. The relative risks (RRs) and 95% confidence intervals (CI) of ADHD, ASD, BD, MDD and schizophrenia were assessed among FDRs of individuals with ASD and ASD with intellectual disability (ASD-ID).
FDRs of individuals with ASD have higher RRs of major psychiatric disorders compared with controls: ASD 17.46 (CI 15.50–19.67), ADHD 3.94 (CI 3.72–4.17), schizophrenia 3.05 (CI 2.74–3.40), BD 2.22 (CI 1.98–2.48) and MDD 1.88 (CI 1.76–2.00). Higher RRs of schizophrenia (4.47, CI 3.95–5.06) and ASD (18.54, CI 16.18–21.23) were observed in FDRs of individuals with both ASD-ID, compared with ASD only.
The risk for major psychiatric disorders was consistently elevated across all types of FDRs of individuals with ASD. FDRs of individuals with ASD-ID are at further higher risk for ASD and schizophrenia. Our results provide leads for future investigation of shared etiologic pathways of ASD, ID and major psychiatric disorders and highlight the importance of mental health care delivered to at-risk families for early diagnoses and interventions.
Whether the first-degree relatives (FDRs) of patients with obsessive-compulsive disorder (OCD) have an increased risk of the major psychiatric disorders, namely schizophrenia, bipolar disorder, OCD, major depressive disorder (MDD), autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD), remains unclear.
Using the Taiwan National Health Insurance Research Database with the whole population sample size (n = 23 258 175), 89 500 FDRs, including parents, offspring, siblings, and twins, of patients with OCD were identified in our study. The relative risks (RRs) of major psychiatric disorders were assessed among FDRs of patients with OCD.
FDRs of patients with OCD had higher RRs of major psychiatric disorders, namely OCD (RR 8.11, 95% confidence interval (CI) 7.68–8.57), bipolar disorder (RR 2.85, 95% CI 2.68–3.04), MDD (RR 2.67, 95% CI 2.58–2.76), ASD (RR 2.38, 95% CI 2.10–2.71), ADHD (RR 2.19, 95% CI 2.07–2.32), and schizophrenia (RR 1.97, 95% CI 1.86–2.09), compared with the total population. Different familial kinships of FDRs, such as parents, offspring, siblings, and twins consistently had increased risks for these disorders. In addition, a dose-dependent relationship was found between the numbers of OCD probands and the risk of each major psychiatric disorder.
The FDRs, including parents, offspring, siblings, and twins, of patients with OCD have a higher risk of OCD, schizophrenia, bipolar disorder, MDD, ADHD, and ASD. The familial co-aggregation of OCD with OCD and other major psychiatric disorders was existent in a dose-dependent manner. Given the increased risks of psychiatric disorders, medical practitioners should closely monitor the mental health of the FDRs of patients with OCD.
The earliest colonisation of oceanic islands by Homo sapiens occurred ~50 000–30 000 years ago in the Western Pacific, yet how this was achieved remains a matter of debate. With a focus on East Asia, the research presented here tests the hypothesis that bamboo rafts were used for these early maritime migrations. The authors review the evidence for Palaeolithic seafaring in East Asia as the context for an experimental archaeology project to build two bamboo watercraft. Sea trials demonstrate the unsuitability of bamboo, at least in East Asia, indicating that more sophisticated and durable vessels would have been required to traverse the Kuroshio Current.
Consumption of a high-fat diet increases fat accumulation and may further lead to inflammation and hepatic injuries. The aim of the study was to investigate the effects of Camellia oleifera seed extract (CSE) on non-alcoholic fatty liver disease (NAFLD). After a 16-week NAFLD-inducing period, rats were assigned to experimental groups fed an NAFLD diet with or without CSE. At the end of the study, we found that consuming CSE decreased the abdominal fat weight and hepatic fat accumulation and modulated circulating adipokine levels. We also found that CSE groups had lower hepatic cytochrome P450 2E1 and transforming growth factor (TGF)-β protein expressions. In addition, we found that CSE consumption may have affected the gut microbiota and reduced toll-like receptor (TLR)-4, myeloid differentiation primary response gene 88, toll/IL-1 receptor domain-containing adaptor-inducing interferon-β (TRIF) expression and proinflammatory cytokine concentrations in the liver. Our results suggest that CSE may alleviate the progression of NAFLD in rats with diet-induced steatosis through reducing fat accumulation and improving lipid metabolism and hepatic inflammation.
The condition of caregivers is important to the quality of care received by people with Parkinson’s disease (PD), especially at the late disease stages. This study addresses the distress placed on caregivers by participants’ neuropsychiatric symptoms at different stages of PD in Taiwan
This prospective study enrolled 108 people with PD. All participants were examined with the Unified Parkinson’s Disease Rating Scale (UPDRS), Neuropsychiatric Inventory (NPI), Mini-Mental State Examination (MMSE), Cognitive Abilities Screening Instrument (CASI), and Clinical Dementia Rating (CDR) scale. Caregiver distress was measured using the Neuropsychiatric Inventory Caregiver Distress Scale (NPI-D). Statistical analysis was used to explore the PD-related factors that contribute to caregiver distress.
The mean follow-up interval in the 108 PD participants were 24.0 ± 10.2 months with no participant lost to follow-up due to death. NPI-distress (the sum of NPI caregiver distress scale across the 12 domains of the NPI) was positively correlated with NPI-sum (the total score across the 12 domains of the NPI) (r = 0.787, p < 0.001), CDR (r = 0.403, p < 0.001), UPRDS (r = 0.276, p = 0.004), and disease duration (r = 0.246, p = 0.002), but negatively correlated with CASI (r = −0.237, p = 0.043) and MMSE (r = −0.281, p < 0.001). Multiple linear regression analysis showed that only NPI-sum and disease duration were independently correlated with NPI-distress.
The disease duration and NPI-sum are independent predictors of caregiver distress in Taiwanese populations with PD. Early detection and reduction of neuropsychiatric symptoms in people with PD can help decrease caregiver distress.
Research suggests an association between metabolic disorders, such as type 2 diabetes mellitus (T2DM), and schizophrenia. However, the risk of metabolic disorders in the unaffected siblings of patients with schizophrenia remains unclear.
Using the Taiwan National Health Insurance Research Database, 3135 unaffected siblings of schizophrenia probands and 12,540 age-/sex-matched control subjects were included and followed up to the end of 2011. Individuals who developed metabolic disorders during the follow-up period were identified.
The unaffected siblings of schizophrenia probands had a higher prevalence of T2DM (3.4% vs. 2.6%, p = 0.010) than the controls. Logistic regression analyses with the adjustment of demographic data revealed that the unaffected siblings of patients with schizophrenia were more likely to develop T2DM (odds ratio [OR]: 1.39, 95% confidence interval [CI]: 1.10–1.75) later in life compared with the control group. Moreover, only female siblings of schizophrenia probands had an increased risk of hypertension (OR: 1.47, 95% CI: 1.07–2.01) during the follow-up compared with the controls.
The unaffected siblings, especially sisters, of schizophrenia probands had a higher prevalence of T2DM and hypertension compared with the controls. Our study revealed a familial link between schizophrenia and T2DM in a large sample. Additional studies are required to investigate the shared pathophysiology of schizophrenia and T2DM.
Bipolar disorder is a highly heritable mental illness that transmits intergeneratively. Previous studies supported that first-degree relatives (FDRs), such as parents, offspring, and siblings, of patients with bipolar disorder, had a higher risk of bipolar disorder. However, whether FDRs of bipolar patients have an increased risk of schizophrenia, major depressive disorder (MDD), autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD) remains unclear.
Among the entire population in Taiwan, 87 639 patients with bipolar disorder and 188 290 FDRs of patients with bipolar disorder were identified in our study. The relative risks (RRs) of major psychiatric disorders were assessed among FDRs of patients with bipolar disorder.
FDRs of patients with bipolar disorder were more likely to have a higher risk of major psychiatric disorders, including bipolar disorder (RR 6.12, 95% confidence interval (CI) 5.95–6.30), MDD (RR 2.89, 95% CI 2.82–2.96), schizophrenia (RR 2.64, 95% CI 2.55–2.73), ADHD (RR 2.21, 95% CI 2.13–2.30), and ASD (RR 2.10, 95% CI 1.92–2.29), than the total population did. These increased risks for major psychiatric disorders were consistent across different familial kinships, such as parents, offspring, siblings, and twins. A dose-dependent relationship was also found between risk of each major psychiatric disorder and numbers of bipolar patients.
Our study was the first study to support the familial coaggregation of bipolar disorder with other major psychiatric disorders, including schizophrenia, MDD, ADHD, and ASD, in a Taiwanese (non-Caucasian) population. Given the elevated risks of major psychiatric disorders, the public health government should pay more attention to the mental health of FDRs of patients with bipolar disorder.
Impaired regulation of blood glucose levels in diabetes mellitus (DM) patients and the associated elevation of blood glucose levels are known to increase the risk of diabetic cardiomyopathy (DC). In the present study, a probiotic bacterium, Lactobacillus reuteri GMN-32, was evaluated for its potential to reduce blood glucose levels and to provide protection against DC risks in streptozotocin (STZ)-induced DM rats. The blood glucose levels of the STZ-induced DM rats when treated with L. reuteri GMN-32 decreased from 4480 to 3620 mg/l (with 107 colony-forming units (cfu)/d) and 3040 mg/l (with 109 cfu/d). Probiotic treatment also reduced the changes in the heart caused by the effects of DM. Furthermore, the Fas/Fas-associated protein with death domain pathway-induced caspase 8-mediated apoptosis that was observed in the cardiomyocytes of the STZ-induced DM rats was also found to be controlled in the probiotic-treated rats. The results highlight that L. reuteri GMN-32 treatment reduces blood glucose levels, inhibits caspase 8-mediated apoptosis and promotes cardiac function in DM rats as observed from their ejection fraction and fractional shortening values. In conclusion, the administration of L. reuteri GMN-32 probiotics can regulate blood glucose levels, protect cardiomyocytes and prevent DC in DM rats.
Glycogen stored in skeletal muscle is the main fuel for endurance exercise. The present study examined the effects of oral hydroxycitrate (HCA) supplementation on post-meal glycogen synthesis in exercised human skeletal muscle. Eight healthy male volunteers (aged 22·0 (se 0·3) years) completed a 60-min cycling exercise at 70–75 % and received HCA or placebo in a crossover design repeated after a 7 d washout period. They consumed 500 mg HCA or placebo with a high-carbohydrate meal (2 g carbohydrate/kg body weight, 80 % carbohydrate, 8 % fat, 12 % protein) for a 3-h post-exercise recovery. Muscle biopsy samples were obtained from vastus lateralis immediately and 3 h after the exercise. We found that HCA supplementation significantly lowered post-meal insulin response with similar glucose level compared to placebo. The rate of glycogen synthesis with the HCA meal was approximately onefold higher than that with the placebo meal. In contrast, GLUT4 protein level after HCA supplementation was significantly decreased below the placebo level, whereas expression of fatty acid translocase (FAT)/CD36 mRNA was significantly increased above the placebo level. Furthermore, HCA supplementation significantly increased energy reliance on fat oxidation, estimated by the gaseous exchange method. However, no differences were found in circulating NEFA and glycerol levels with the HCA meal compared with the placebo meal. The present study reports the first evidence that HCA supplementation enhanced glycogen synthesis rate in exercised human skeletal muscle and improved post-meal insulin sensitivity.