Changes in cognitive function after a 12-week POWER rehabilitation in older adults with schizophrenia and frailty.

BACKGROUND: The effectiveness of isolated resistance training (RT) on cognitive function among older adults with schizophrenia is insufficiently investigated. This study investigated the effectiveness of 12-weeks POWER rehabilitation, a novel RT regimen, on cognitive function among older patients with schizophrenia and frailty. METHODS: Thirty-two older adults with schizophrenia and frailty were enrolled and randomized to receive either a 12-week, twice weekly POWER rehabilitation, or without add-on training. Cognitive functioning was assessed using mini-mental state examination (MMSE), digit symbol substitution test, color trail task (CTT), and digit span task (DST). Physical performance was assessed by walking speed and hand grip strength. The generalized estimating equations was used to compare pre- and post-training outcome measure between groups. RESULTS: Between-group analysis revealed significant improvement in CTT1 and hand grip strength in the intervention group compared to the controls. Subgroup analyses showed CTT1 performance significantly improved after 12 weeks of POWER rehabilitation in the intervention group (time, p < .001), independent of age, educational level, global cognition, depressive symptoms, and psychotropic medication use. Increased hand grip strength was significantly associated with improved performance in MMSE, CTT1, and DST forward at study endpoint. CONCLUSION: A 12-week POWER rehabilitation for older patients with schizophrenia and frailty is safe and feasible, and may benefit physical and some domains of cognitive functioning.

Poor subjective sleep quality and trait impulsivity in patients with bipolar disorder.

BACKGROUND: Sleep disturbance and impulsivity are key components of mood vulnerability in bipolar disorder (BD), but few studies have assessed the association between these two symptoms among patients with BD. METHODS: Forty-seven euthymic patients with bipolar I disorder (BDI) or bipolar II disorder (BDII) and 58 age- and sex-matched healthy controls were enrolled in this cross-sectional study. Trait impulsivity was measured using the Barratt Impulsiveness Scale Version 11 (BIS-11), which yielded 3 second-order factors: attention, motor, and non-planning. Subjective sleep quality was assessed using the self-reported Pittsburgh Sleep Quality Index (PSQI). General linear models (GLMs) were used to assess the associations between subjective poor sleep and trait impulsivity with multiple testing corrections. RESULTS: Patients with BD scored higher in BIS-11 and PSQI than healthy controls. PSQI total scores positively correlated with BIS-11 total scores, while sleep disturbance and daytime dysfunction were associated with attentional impulsiveness after controlling for covariates. Participants with higher PSQI total scores (>10) had higher scores in BIS-11 total, attention, and non-planning than those with low PSQI scores (≤5). CONCLUSION: These findings support the hypothesis that poor sleep quality might lead to impulsivity and add to the growing evidence that improving sleep quality may be a therapeutic target for patients with BD.

Brain structural abnormalities and trait impulsivity in suicidal and non-suicidal patients with bipolar disorder.

BACKGROUND: Impulsivity is a characteristic of patients with bipolar disorder (BD) and may result in a higher risk of suicide attempt (SA). Although brain structural abnormalities have been suggested in the pathophysiology of BD, the relationship to impulsivity and suicide in BD is still not clear. METHODS: 52 euthymic patients with BD (26 of them had a history of SA) and 56 age- and sex-matched healthy controls were recruited. All participants received clinical assessment, including Barratt impulsiveness scale (BIS), and underwent structural magnetic resonance imaging examination. An automated surface-based method (FreeSurfer) was used to measure brain volume and cortical surface area. A general linear model was applied to analyze the association between brain-wise greater gray matter volume (GMV), surface area and BIS scores separately for BD patients with and without SA history. RESULTS: BD patients with SA history scored higher in BIS total score and subscores in attention, motor, cognitive complexity and cognitive instability than those without SA history and controls (all p < 0.01). In patients with SA history, higher BIS scores were associated with greater GMV in the left pars triangularis and greater surface area in left pars opercularis (all p < 0.01). BD patients with SA history showed a greater GMV in inferior frontal gyrus than patients without SA history (p < 0.05). LIMITATION: The cross-sectional design precluded examination of chronological relationships of SA, brain structural abnormalities, and trait impulsivity among BD. CONCLUSIONS: The findings indicate that the prefrontal cortex, especially the left inferior frontal gyrus, plays a vital role in trait impulsivity and suicidal behavior among patients with BD.

A longitudinal study of the association between pro-inflammatory cytokines and mood symptoms in bipolar disorder.

BACKGROUND: Because of a relative dearth of longitudinal studies, the directionality of the relationship between mood and inflammation among patients with bipolar disorder (BD) is still unclear. We aimed to investigate the longitudinal associations of pro-inflammatory markers with mood symptom severity in BD. METHODS: Hundred and thirty-two adult patients with BD were enrolled. At the baseline and 1-year follow-up visit, all participants received mood assessment with Montgomery Åsberg depression rating scale (MADRS) and Young mania rating scale, and underwent blood draws to quantify metabolic profile and serum levels of the pro-inflammatory markers, including soluble interleukin-6 receptor, soluble tumor necrosis factor-α receptor type 1 (sTNF-αR1), monocyte chemoattractant protein-1, and C-reactive protein. A four-factor model of MADRS, consisting of sadness, negative thoughts, detachment, and neurovegetative symptoms, were applied. RESULTS: At baseline, 65 patients with BD were in depressed state, and 67 patients with BD were in euthymic state. Among patients in depressed state, baseline MADRS total score positively correlated with sTNF-αR1 level at follow-up. While baseline sTNF-αR1 level positively predicted sadness symptom in euthymic patients with BD who later developed depression (n = 22), sadness in patients with bipolar depression predicted later increase in serum sTNF-αR1 level even after remission (n = 17). Moreover, lithium had a stronger effect of lowering peripheral sTNF-αR1 level as compared with other mood stabilizers. CONCLUSION: Our results indicate the bidirectional inflammation-depression relationship in BD.

Exploring the role of hub and network dysfunction in brain connectomes of schizophrenia using functional magnetic resonance imaging.

Introduction: Pathophysiological etiology of schizophrenia remains unclear due to the heterogeneous nature of its biological and clinical manifestations. Dysfunctional communication among large-scale brain networks and hub nodes have been reported. In this study, an exploratory approach was adopted to evaluate the dysfunctional connectome of brain in schizophrenia. Methods: Two hundred adult individuals with schizophrenia and 200 healthy controls were recruited from Taipei Veterans General Hospital. All subjects received functional magnetic resonance imaging (fMRI) scanning. Functional connectivity (FC) between parcellated brain regions were obtained. Pair-wise brain regions with significantly different functional connectivity among the two groups were identified and further analyzed for their concurrent ratio of connectomic differences with another solitary brain region (single-FC dysfunction) or dynamically interconnected brain network (network-FC dysfunction). Results: The right thalamus had the highest number of significantly different pair-wise functional connectivity between schizophrenia and control groups, followed by the left thalamus and the right middle frontal gyrus. For individual brain regions, dysfunctional single-FCs and network-FCs could be found concurrently. Dysfunctional single-FCs distributed extensively in the whole brain of schizophrenia patients, but overlapped in similar groups of brain nodes. A dysfunctional module could be formed, with thalamus being the key dysfunctional hub. Discussion: The thalamus can be a critical hub in the brain that its dysfunctional connectome with other brain regions is significant in schizophrenia patients. Interconnections between dysfunctional FCs for individual brain regions may provide future guide to identify critical brain pathology associated with schizophrenia.

Pro-inflammatory cytokines and cognitive dysfunction among patients with bipolar disorder and major depression.

AIM: Bipolar disorder and major depressive disorder (MDD) have been demonstrated to be associated with proinflammatory states and cognitive function deficits. We aimed to investigate the differences of cognitive function and proinflammatory cytokines between patients with bipolar I disorder (BDI), bipolar II disorder (BDII), and MDD. METHODS: Thirty-seven patients with BDI, 33 with BDII, 25 with MDD, and 54 age-, sex-matched controls were enrolled. All patients had a clinical global impression-severity scale ≤2. Serum levels of proinflammatory markers, including soluble interleukin-6 receptor, C-reactive protein, and soluble tumor necrosis factor receptor 1 (sTNF-αR1) were measured. Performance in the Word List Memory Task (WLMT), Wisconsin Card Sorting Task (WCST), 2-back task, Go/No-Go task, and divided attention task was assessed. RESULTS: Patients with BDI had higher levels of sTNF-αR1 than patients with MDD and controls (P < 0.001). Patients with BDI performed worse on WLMT, WCST, 2-back task, divided attention_visual and divided attention_auditory tasks than the other three groups (all P < 0.05). Furthermore, sTNF-αR1 levels were negatively correlated with cognitive function measured using the WLMT and divided attention_auditory (all P < 0.05). CONCLUSIONS: Patients with BDI had higher levels of sTNF-αR1 and cognitive function impairments than the remaining groups. Future studies are needed to explore the pathophysiology of sTNF-αR1 in the contribution of cognitive alterations.

Predictors of emergency department visit among people with dementia in Taiwan.

BACKGROUND: We aimed to identify predictors of emergency department (ED) visit by people with dementia (PWDs) and their caregivers with a one-year follow-up in a country with public health system. METHODS: Data were collected from a national dementia registration survey. Andersen's Behavioral Model of Health Services Use was used. Variables such as demographic data of PWDs and their caregivers, caregivers' monthly income, the relationship between PWD and caregivers, the severity of dementia (clinical dementia rating, CDR), physical comorbidities, cognitive function (mini-mental state examination, MMSE), and activities of daily living of PWDs, the caregiver burden, and neuropsychiatric symptoms (assessed by the Neuropsychiatric Inventory Questionnaire) were included in the analyses. RESULTS: A total of 1,227 PWDs-caregiver dyads completed the survey, and 405 (33%) of PWDs visited ED during the one-year follow-up. Multivariable logistic analyses revealed that older age of PWDs (odds ratio [OR] = 1.03, 95% confidence interval [CI] = 1.01-1.05), more severe dementia (CDR; OR = 1.42, 95% CI = 1.09-1.86), higher cognitive function (MMSE; OR = 1.04, 95% CI = 1.01-1.07), and having a female family caregiver (OR = 1.50, 95% CI = 1.13-2.01) were predictors of ED visit. CONCLUSION: Our study results provided information for healthcare providers and policy makers to target models of care that support PWD and their caregivers and reduce the need for ED visits.

RETRACTED - Risk factors for mild behavioral impairment in non-demented geriatrics: a population-based survey in Taiwan.

OBJECTIVES: To investigate potential risk factors for mild behavioral impairment (MBI) among non-demented geriatrics. DESIGN: Population-based, cross-sectional survey. SETTING: Taiwan Alzheimer Disease Association (TADA) Database. PARTICIPANTS: Participants were selected by multistage random sampling of all Taiwan counties. They received in-person interviews between December 2011 and March 2013. MEASUREMENTS: 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. RESULTS: 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). CONCLUSIONS: Good sleep was associated with lower MBI risk. Underweight, lower education, medical comorbidities of cancer, hypertension, hyperlipidemia were predictive of MBI.

Pro-inflammatory cytokines and suicidal behavior among patients with bipolar I disorder.

OBJECTIVE: Suicidal behavior and different mood states of bipolar I disorder (BD) have been shown to be associated with dysregulated proinflammatory cytokines. Only a few studies have examined the association between inflammation and SB in BD, and the association between proinflammatory cytokines, SB, and cognitive deficits in patients with BD remains unclear. METHODS: 77 patients with BD and 61 age-/sex-matched healthy controls were recruited. Patients were divided into two groups: with suicidal ideation (SI; n = 21) and no SI (n = 56). SI was defined by a score of ≥1 in item 10 of Montgomery Åsberg Depression Rating Scale. Levels of proinflammatory cytokines, including soluble interleukin-6 receptor (sIL-6R), soluble tumor necrosis factor-α receptor type 1 (sTNF-αR1), and C-reactive protein (CRP), were measured, and cognitive function was assessed using 2-back task and Go/No-Go task. RESULTS: Patients with SI had higher levels of sTNF-αR1 than those without SI and the controls (p = .004). BD patients with or without a history of suicide attempt had higher levels of CRP than the controls. SI was associated with serum levels of sTNF-αR1 and IL-6sR, even after additionally controlling for working memory and inhibitory control (p < .05). CONCLUSION: This study indicates that serum levels of sTNF-αR1 have distinct differences between BD patients with or without SI, and our findings strengthen the hypothesis of a link between suicidal behavior and neuro-inflammation pathophysiology in BD.

Treatment response and age of onset as risk indicators for parkinson disease in patients with major depressive disorder: A nationwide longitudinal study.

BACKGROUND: Individuals with major depressive disorder (MDD) have a higher risk of developing Parkinson disease (PD). This study investigated whether response to treatment with antidepressants for MDD can determine patients at risk of developing PD later in life. METHODS: We enrolled 3303 patients with newly-diagnosed MDD and 13,212 controls between 2002 and 2004 using Taiwan's Nationwide Health Insurance Research Database. We stratified patients with MDD according to the number of antidepressant regimens prescribed to them and the age at MDD onset and followed all participants until the end of 2013. During follow-up, we evaluated patients for the possibility of developing PD. RESULTS: Patients with MDD had a greater likelihood of developing PD than controls. Patients with difficult-to-treat (DTT) MDD had a higher risk of developing PD than the other MDD subgroups (hazard ratio [HR] = 3.44, 95% confidence interval [95% CI]: = 1.99-5.95). When stratified by age (<50, 50-65, >65 years), DTT patients with middle-age or late-onset MDD exhibited elevated risks of developing PD (50-65 years: HR: 7.03, 95% CI: 2.95-16.76; >65 years: HR: 2.89, 95% CI: 1.26-6.65). DISCUSSION: Patients with MDD and an onset age of >50 years who responded poorly to antidepressant treatment have an associated higher risk of subsequently developing PD. Therefore, when treating patients with MDD, clinicians should provide intensive antidepressant treatment and evaluations for PD so that risk-prevention measures can be implemented upon MDD diagnosis.

Association between gastrointestinal symptoms and depression among older adults in Taiwan: A cross-sectional study.

BACKGROUND: Older adults with depression more frequently experience somatic and gastrointestinal (GI) problems compared with people without depression and younger adults with depression. However, whether GI symptoms are predictive of elevated rates of depression among older adults is unclear. METHODS: We enrolled 106 older adults (>60 years old); 69 had late-life depression (LLD), and 37 were controls. All participants gave ratings on the Gastrointestinal Symptom Rating Scale (GSRS) and Hamilton Depression Rating Scale. Food consumption was assessed using a food frequency questionnaire, and a Mediterranean diet score was used as a covariate. RESULTS: Compared with the controls, patients with LLD reported higher levels of depressive and GI symptoms and reported more reflux, abdominal pain, and dyspepsia symptoms, and these symptoms were correlated with Hamilton Depression Rating Scale scores (GSRS total: ß = 0.47; reflux: ß = 1.47; abdominal pain: ß = 1.98; dyspepsia: ß = 1.02; all p < 0.01). After demographic variables and Mediterranean diet score were controlled for, a logistic regression analysis indicated that total GSRS score was an independent determinant of LLD (odds ratio: 1.20, 95% CI: 1.04-1.38). Moreover, a stratified analysis by depression severity indicated that higher total GSRS score may contribute to greater depression severity (odds ratio: 1.25, 95% CI: 1.04-1.52). CONCLUSION: We provide evidence that GI symptoms are associated with depressive symptoms among patients with LLD. Older people with more specific GI symptoms, such as reflux, abdominal pain, and dyspepsia, are potentially at greater risk of having LLD.

Treatment-Resistant depression enhances risks of dementia and alzheimer's disease: A nationwide longitudinal study.

BACKGROUND: Previous evidence indicates late-onset depression or depression with greater severity are associated with subsequent risk of dementia or Alzheimer's disease (AD). However, whether treatment-resistant depression is associated with such risks remain elusive. METHODS: Using the Taiwan Nationwide Health Insurance Research Database, 3,345 patients with newly-diagnosed major depressive disorder (MDD) and 13,380 well-matched controls were enrolled between 2002 and 2004. MDD patients were stratified according to their treatment response to adequate antidepressant trials, and all participants were followed up until the end of 2013. Those who developed dementia and AD were identified. RESULTS: MDD patients were more likely to develop dementia and AD than controls. Difficult-to-treat patients (i.e., DTT; those who failed to respond to at least two adequate antidepressant trials) had the highest risk of developing dementia (hazard ratio [HR] = 5.19) and AD (HR 4.44), whereas easy-to-treat patients (i.e., ETT-1; those who had no prescription of antidepressants) had the lowest risk of developing dementia (HR 2.37) and AD (HR 2.59) compared with controls. Subsequent analysis demonstrated that only among patients with late-onset depression (age > 65 years), DTT patients consistently showed higher risks and faster development of dementia (HR 6.64, mean: 1.45 yr) and AD (HR 4.97, mean: 1.67 yr) than did ETT-1 patients and controls. LIMITATIONS: Subjects who have not received medical examination were not included as diagnosis were determined by ICD codes. Also, longer follow-up period might be needed for the younger group. CONCLUSIONS: Late-onset treatment-resistant depression is associated with an elevated risk of dementia and AD.

Post-traumatic Stress Disorder and Risk of Parkinson Disease: A Nationwide Longitudinal Study.

OBJECTIVE: Increasing evidence has suggested a relationship between post-traumatic stress disorder (PTSD) and neurodegenerative disorder, such as Alzheimer disease. The association between PTSD and Parkinson disease (PD), however, remains unclear. METHOD: Using the Taiwan National Health Insurance Research Database, 7,280 subjects (1,456 patients aged ≥45 years with PTSD and 5,824 age-/sex-matched individuals without PTSD) were enrolled between 2002 and 2009 and followed to the end of 2011. Subjects who developed PD during the follow-up period were identified. RESULTS: An increased risk of developing PD was found in patients with PTSD (Wald χ2 = 12.061, hazard ratio [HR]: 3.46, 95% confidence interval [CI]: 1.72-6.96) compared with individuals without PTSD, after adjusting for demographic data and medical and psychiatric comorbidities. The sensitivity tests after excluding the first year observation (Wald χ2 = 7.948, HR: 3.01, 95% CI: 1.40-6.46) and the first 3-year observation (Wald χ2 = 5.099, HR: 3.07, 95% CI: 1.16-8.15) were consistent. CONCLUSIONS: Patients with PTSD had an elevated risk of developing PD in later life. Further studies would be required to clarify the exact pathophysiology between PTSD and PD and to investigate whether the prompt intervention for PTSD may reduce this risk.

Increased matriptase zymogen activation in inflammatory skin disorders.

Matriptase, a type 2 transmembrane serine protease, and its inhibitor hepatocyte growth factor activator inhibitor (HAI)-1 are required for normal epidermal barrier function, and matriptase activity is tightly regulated during this process. We therefore hypothesized that this protease system might be deregulated in skin disease. To test this, we examined the level and activation state of matriptase in examples of 23 human skin disorders. We first examined matriptase and HAI-1 protein distribution in normal epidermis. Matriptase was detected at high levels at cell-cell junctions in the basal layer and spinous layers but was present at minimal levels in the granular layer. HAI-1 was distributed in a similar pattern, except that high-level expression was retained in the granular layer. This pattern of expression was retained in most skin disorders. We next examined the distribution of activated matriptase. Although activated matriptase is not detected in normal epidermis, a dramatic increase is seen in keratinocytes at the site of inflammation in 16 different skin diseases. To gain further evidence that activation is associated with inflammatory stimuli, we challenged HaCaT cells with acidic pH or H(2)O(2) and observed matriptase activation. These findings suggest that inflammation-associated reactive oxygen species and tissue acidity may enhance matriptase activation in some skin diseases.