Obesity paradox and stroke outcomes according to stroke subtype: a propensity score-matched analysis.

OBJECTIVE: Obesity has traditionally been considered a risk factor for ischemic stroke. However, some clinical observations have reported a complex relationship between patients who are overweight or obese with paradoxically better stroke outcomes. Stroke subtypes have differing distributions of risk factors, so this study aimed to explain the relationship between body mass index (BMI) and functional prognosis according to stroke subtype. METHODS: A prospective institutional database on stroke was accessed between March 2014 and December 2021, and consecutive patients with ischemic stroke were retrospectively selected. BMI was categorized into five groups (underweight, normal weight, overweight, obese, and morbid obesity). The outcome of interest in this study was the modified Rankin Scale (mRS) at 90 d, which was divided into favorable (mRS = 0-2) and unfavorable (mRS ≥ 3) groups. The relationship between functional outcome and BMI was analyzed according to stroke subtype. RESULTS: Among 2779 patients with stroke, 913 (32.9%) had unfavorable outcomes. After a propensity score-matched analysis, obesity was inversely associated with unfavorable outcomes (adjusted odds ratio [aOR] = 0.61, 95% confidence interval [95% CI]: 0.46-0.80) in all patients with stroke. Among the stroke subtypes, overweight (aOR = 0.38, 95% CI: 0.20-0.74) and obese (aOR = 0.40, 95% CI: 0.21-0.76) groups were inversely associated with unfavorable outcomes in the cardioembolism subtype. Obesity (aOR = 0.55, 95% CI: 0.32-0.95) was inversely associated with unfavorable outcomes in the small vessel disease subtype. There was no significant relationship between stroke outcome and BMI classification in the large artery disease subtype. CONCLUSIONS: These findings suggest that the obesity paradox in ischemic stroke outcomes might differ according to the stroke subtype.

Quantitative evaluation of hand motor function using a gyrosensor in mild and moderate carpal tunnel syndrome.

INTRODUCTION: The objective of this study was to determine whether patients with carpal tunnel syndrome (CTS) manifest changes in early-stage motor function and to investigate the utility of a gyrosensor for quantitative evaluation of motor function. METHODS: Angular velocity signal was measured during finger tapping in 52 patients with mild-to-moderate CTS and 45 controls. Four finger-tapping performance (FTP) values-root-mean-squared (RMS) velocity, RMS angle, peak power, and total power-were derived from the signal. RESULTS: All FTP values were significantly lower in patients with CTS than in controls (P = 0.001 or P < 0.001). There were no significant differences between the mild and moderate CTS subgroups. DISCUSSION: FTP measurement with a gyrosensor represents a valuable tool for the evaluation of median nerve motor function in patients with CTS. It facilitates the detection of subclinical motor dysfunction in patients with early stage CTS. Muscle Nerve 59:465-469, 2019.

Using the Region of Interest from Time-of-Flight Magnetic Resonance Angiography to Differentiate Between Intracranial Arterial Dissection and True Atherosclerotic Stenosis.

BACKGROUND: Noncontrast three-dimensional time-of-flight magnetic resonance angiography (3D TOF MRA) is commonly used to examine intracranial arterial stenosis, although it can be difficult to identify the etiology of the stenosis. Our aim was to determine the effectiveness of 3D TOF MRA in differentiating an intracranial arterial dissection from atherosclerosis. METHODS: During 2015-2017, 356 patients had confirmed intracranial arterial stenosis based on high resolution-magnetic resonance imaging. This study ultimately included 51 patients with severe focal stenosis that was caused by dissection and atherosclerosis. We compared the dissection group with the atherosclerotic narrowing group by measuring the region-of-interest (ROI) values 3 mm proximal and 3 mm distal from sites of severe focal stenosis. RESULTS: A significant difference was observed between the median ROI difference values in the dissection group (n = 18) and the atherosclerosis group (n = 33; 35.6 [20.9-78.4] vs. 165.5 [99.8-328.5]; p < 0.001). A receiver operating characteristic curve was prepared to distinguish between dissection and atherosclerosis using the ROI difference values. The area under the curve was 0.919 (sensitivity 75.8%, specificity 94.4%). The optimal cutoff value for using ROI to distinguish between dissection and atherosclerosis was found to be 99.0 based on the Youden's index. CONCLUSION: The ROI difference value from 3D TOF MRA could help distinguish between dissection and atherosclerosis. If the ROI difference value from 3D TOF MRA is small (< 99.0), detailed testing should be performed to identify dissection.

Increased plasma complement factor H is associated with geriatric depression.

ABSTRACTBackground:Complement factor H (CFH) plays a key role in regulating the cascade of the alternative pathway of the complement system. Dysregulation of CFH may be involved in the pathophysiology of various inflammation-mediated diseases including neuropsychiatric illnesses. This study aimed to investigate this relationship by examining determining CFH levels in elderly individuals with and without depression. METHODS: A total of 152 elderly individuals (major depressive disorder (MDD) group, n = 76; comparison sample, n = 76) were selected from the Ansan Geriatric study. The plasma level of CFH was measured. MDD was diagnosed with the Mini-International Neuropsychiatric Interview as per DSM-IV criteria. The severity of depression was evaluated with the geriatric depression scale (GDS). Mean CFH levels were compared using the Mann-Whitney U test. After adjusting for possible confounding factors including age, sex, marital status, education, alcohol use, hemoglobin levels, and the Korean version of the Mini-Mental State Examination (MMSE-KC), a multiple regression analysis was conducted. The GDS score and plasma level of CFH were analyzed using Spearman's correlation. RESULTS: Plasma CFH level was significantly higher in individuals with MDD than in the comparison sample (289.51 ± 21.16 vs. 339.67 ± 66.23, p < 0.001). In a regression model adjusted for possible confounders, CFH was significantly associated with geriatric depression (p < 0.001). CFH levels were not significantly related to GDS scores in the depressed group. CONCLUSION: This study revealed an association between high plasma levels of CFH and geriatric depression, thereby suggesting the alternative pathway of the complement system contributing to the development of geriatric depression.

Free fatty acid as an outcome predictor of atrial fibrillation-associated stroke.

OBJECTIVE: We investigated whether baseline plasma free fatty acid (FFA) concentration is associated with any (ischemic/hemorrhagic) stroke, ischemic stroke/systemic embolism (ISSE), or ischemic stroke among stroke survivors with atrial fibrillation (A-fib). Moreover, we compared the outcome predictability of FFA with previously adopted models, including the CHADS2 and CHA2 DS2 -VASc scoring systems. METHODS: We analyzed data from 279 stroke patients with A-fib and investigated the association between plasma FFA concentration and outcomes using Cox regression models with competing risk analyses. RESULTS: Median follow-up period was 17.5 months. During the study period, any stroke, ISSE, and ischemic stroke occurred in 22, 21, and 17 patients, respectively. The cumulative risk for any stroke, ISSE, and ischemic stroke were 5.1%, 4.7%, and 4.2% at the end of the first year and 14.8%, 12.1%, and 10.8% at the end of the third year, respectively. After adjusting covariates (model 1), baseline FFA concentration was associated with recurrence of any stroke (hazard ratio [HR] = 1.774, 95% confidence interval [CI] = 1.124-2.801, per 1mEq/l increment of FFA). FFA showed a trend association with ISSE (HR = 1.569, 95% CI = 0.950-2.592) and ischemic stroke (HR = 1.630, 95% CI = 0.967-2.746). In adjusted models including CHADS2 or CHA2 DS2 -VASc score as a covariate, (models 2 and 3) FFA was still shown to be an independent predictor of any stroke and ischemic stroke. There was a significant or trend association between FFA and ISSE. INTERPRETATION: FFA may be a potential biomarker that predicts outcome events in stroke with A-fib along with the CHADS2 and CHA2 DS2 -VASc scoring systems.

Subjective Memory Change, Mood, and Cerebrovascular Risk Factors in Older African Americans.

OBJECTIVE: Subjective memory change (SMC) in older individuals may represent a harbinger of cognitive decline. This study examined the factors associated with SMC in older African Americans (AA), who have greater risk of developing dementia. We predicted that symptoms of depression and anxiety, as well as the total number of cerebrovascular risk factors (tCVRFs), but not performances on objective memory measures, would be positively associated with SMC. METHODS: Ninety-six AA completed brief cognitive testing and answered questions about mood and memory at their primary care appointment. Vascular data were obtained from medical records. RESULTS: Symptoms of depression and anxiety, but not performances on objective memory measures, were positively associated with SMC, t(χ2(1) = 16.55 and 12.94, respectively, both P < .001). In nondepressed participants, the tCVRF was important in distinguishing between those with and without SMC. CONCLUSIONS: In older AA, symptoms of depression or anxiety were associated with SMC. In nondepressed AA, the tCVRFs were important in distinguishing between those with and without SMC.

Blood Pressure Variability and Cognitive Function Among Older African Americans: Introducing a New Blood Pressure Variability Measure.

BACKGROUND: Although blood pressure (BP) variability has been reported to be associated with cognitive impairment, whether this relationship affects African Americans has been unclear. We sought correlations between systolic and diastolic BP variability and cognitive function in community-dwelling older African Americans, and introduced a new BP variability measure that can be applied to BP data collected in clinical practice. METHODS: We assessed cognitive function in 94 cognitively normal older African Americans using the Mini-Mental State Examination (MMSE) and the Computer Assessment of Mild Cognitive Impairment (CAMCI). We used BP measurements taken at the patients' three most recent primary care clinic visits to generate three traditional BP variability indices, range, standard deviation, and coefficient of variation, plus a new index, random slope, which accounts for unequal BP measurement intervals within and across patients. RESULTS: MMSE scores did not correlate with any of the BP variability indices. Patients with greater diastolic BP variability were less accurate on the CAMCI verbal memory and incidental memory tasks. Results were similar across the four BP variability indices. CONCLUSIONS: In a sample of cognitively intact older African American adults, BP variability did not correlate with global cognitive function, as measured by the MMSE. However, higher diastolic BP variability correlated with poorer verbal and incidental memory. By accounting for differences in BP measurement intervals, our new BP variability index may help alert primary care physicians to patients at particular risk for cognitive decline.

Informant questionnaire on cognitive decline in the elderly (IQCODE) for classifying cognitive dysfunction as cognitively normal, mild cognitive impairment, and dementia.

BACKGROUND: The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) is a reliable, validated informant-based instrument in screening for cognitive dysfunction. However, previous studies have evaluated only the ability to discriminate dichotomously, such as dementia from cognitively normal (CN) individuals or mild cognitive impairment (MCI) from CN. This study investigated the ability of the IQCODE to classify not only dichotomous but also multiple stages of cognitive dysfunction. METHODS: We examined 228 consecutive participants (76 CN, 76 with MCI, and 76 with dementia). Receiver operating characteristic (ROC) curves determined dichotomous classification parameters. Multi-category ROC surfaces were evaluated to classify three stages of cognitive dysfunction. RESULTS: Dichotomous classification using the ROC curve analyses showed that the area under the ROC curve was 0.91 for dementia from participants without dementia and 0.71 for MCI from CN. Simultaneous multi-category classification analyses showed that the volume under the ROC surface was 0.61 and the derived optimal cut-off points were 3.15 and 3.73 for CN, MCI, and dementia. The Youden index for the IQCODE was estimated as 0.51 and the derived optimal cut-off points were 3.33 and 3.70. The overall classification accuracy by the VUS was 58.3% and that by the Youden index 61.8%. CONCLUSIONS: IQCODE is useful to classify the dichotomous and multi-category stages of cognitive dysfunction.

Correlation between overactive bladder symptom score and neuropsychological parameters in Alzheimer's disease patients with lower urinary tract symptom.

PURPOSE: To examine an association between the overactive bladder symptom score (OABSS) and neuropsychological parameters. Moreover, we investigate the factors that affect each item in the questionnaire. MATERIALS AND METHODS: A total of 376 patients (males: 184; females: 192) with probable Alzheimer's disease (AD) were recruited. Cognitive testing was conducted using the Mini Mental Status Examination (MMSE), Clinical Dementia Rating (CDR) scale, Global Deterioration Scale (GDS), and Barthel Activities of Daily Living (ADL). Lower urinary tract symptom (LUTS) was assessed using OABSS and voiding diary. RESULTS: The prevalence of overactive bladder (OAB) (defined as OABSS ≥3 with na urgency score of ≥2) in patients with AD was 72.6%. Among the OAB subjects, the most common severity of symptom was moderate (72.6%), followed by mild (21.2%), and severe (5.8%). It was found that OABSS had a very high correlation with aging (r=0.75; p<0.001). When compared with neuropsychological parameters, it was found that OABSS was highly correlated with the CDR scores (r=0.446; p<0.001). However, no significant correlation was found between the changes in OABSS scores and those in other neuropsychological parameters. Based on the individual symptom scores, urgency incontinence was highly correlated with the CDR scores (r=0.43; p<0.001). CONCLUSIONS: OABSS is a useful tool in assessing AD patients with LUTS. There was a consistent positive association between OABSS severity, including urgency incontinence, and CDR scores.

Group- and Home-Based Cognitive Intervention for Patients with Mild Cognitive Impairment: A Randomized Controlled Trial.

BACKGROUND: We examined the efficacy of group-based cognitive intervention (GCI) and home-based cognitive intervention (HCI) in amnestic mild cognitive impairment (aMCI) and intervention effects on serum brain-derived neurotrophic factor (BDNF). METHODS: In this randomized and rater-blinded trial, 293 patients with aMCI from 18 nationwide hospitals were randomized: 96 to the GCI group, 98 to the HCI group and 99 to the control group. For 12 weeks, subjects receiving GCI participated twice per week in group sessions led by trained instructors, and those receiving HCI completed homework materials 5 days per week. They were assessed at baseline, postintervention (PI) and at the 6-month follow-up after the intervention. The primary endpoint was the change from baseline to PI in the modified Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog). RESULTS: In comparison to the controls (a 0.8-point decrease), the subjects receiving GCI (a 2.3-point decrease, p = 0.01) or HCI (a 2.5-point decrease, p = 0.02) showed significant improvements in the modified ADAS-Cog at PI, respectively. By the 6-month follow-up, those receiving GCI or HCI had better scores in the modified ADAS-Cog than the controls. The changes in BDNF levels significantly correlated with the changes in the modified ADAS-Cog in the GCI (r = -0.29, p = 0.02 at PI) and HCI (r = -0.27, p = 0.03 at 6-month follow-up) groups, respectively. CONCLUSIONS: The GCI and HCI resulted in cognitive improvements in aMCI. An enhanced brain plasticity may be a component of the mechanism underpinning the cognitive improvements associated with the cognitive interventions.

Headache characteristics of uncomplicated intracranial vertebral artery dissection and validation of ICHD-3 beta diagnostic criteria for headache attributed to intracranial artery dissection.

BACKGROUND AND PURPOSE: Headache may be a warning sign of subsequent stroke in patients with vertebral artery dissection (VAD). Even though the headache characteristics of VAD have been described predominantly in patients with extracranial VAD and neurological complications, headache semiology is not well known in patients with uncomplicated intracranial vertebral artery dissection (ICVAD). In the present study, we attempt to identify the headache semiology that characterizes ICVAD and validate the revised version of the International Classification of Headache Disorders (ICHD-3 beta) criteria for headache attributed to intracranial artery dissection. METHODS: Six patients with neurologically uncomplicated ICVAD presented at a participating medical center, and eight similar patients were reviewed in the literature. Combining these data, we analyzed headache characteristics of patients with uncomplicated ICVAD according to their pain onset and duration, nature, intensity, location, aggravating and relieving factors, associated symptoms, response to medication, and prognosis. RESULTS: Headache in uncomplicated ICVAD usually has an acute mode of onset (11/14) and persistent (10/14) temporal feature. Pain that has a throbbing quality (nine of 14) and severe intensity (13/14) on the ipsilesional (10/14) and occipitonuchal area (12/14) is a headache prototype in ICVAD. Additionally, headache was intensified by head flexion and rotation (three of six), and relieved by head extension and supine positioning (five of six). Headache of all patients in the present study fulfilled the ICHD-3 beta criteria. CONCLUSION: Headache semiology of uncomplicated ICVAD is mostly homogenous in the present study. These characteristics may be helpful in the diagnosis of uncomplicated ICVAD.

Is there an MCI reversion to cognitively normal? Analysis of Alzheimer's disease biomarkers profiles.

BACKGROUND: We investigated the characteristics of Alzheimer's disease (AD) biomarkers for mild cognitive impairment (MCI) reversion to cognitively normal (CN). METHODS: Of a total of 1,233 participants from the ADNI database, 42 participants with MCI reversion to CN (MCIr), 778 with MCI, and 413 CN were obtained. We evaluated demographics, clinical outcomes, medication use, MCI type, and AD biomarkers, including genetic, cerebrospinal fluid, imaging, and neuropsychological data. RESULTS: This study showed that the differences between MCIr and CN were only age, Mini-Mental State Examination, and Clinical Dementia Rating - Sum of Boxes, but the differences between MCIr and MCI were not only clinical outcomes but also AD biomarkers, including genetic, cerebrospinal fluid, imaging, and neuropsychological data. Overall, MCIr may be similar to CN and not MCI in clinical characteristics. CONCLUSIONS: With assessment of MCI reversion to CN, the possibility of false-positive errors should be considered. With the assistance of AD biomarkers, MCI can be evaluated more accurately than the conventional criteria.

Reversed corrective saccades during head impulse test in acute cerebellar dysfunction.

Patients with cerebellar lesions may show horizontal (positive)- or downward (perverted)-corrective saccades during horizontal head impulse test (HIT). However, corrective saccades in the direction of head rotation (reversed corrective saccades) have not been reported during HIT. We present two patients who showed reversed corrective saccades during horizontal HIT as an initial sign of acute cerebellitis. In contrast to the corrective saccades mostly observed in peripheral vestibular paresis, this paradoxical response indicates abnormally increased vestibulo-ocular responses due to cerebellar disinhibition over the vestibulo-ocular reflex. This paradoxical response should be considered an additional bedside cerebellar sign.

Urinary incontinence in patients with Alzheimer's disease: relationship between symptom status and urodynamic diagnoses.

OBJECTIVE: To assess factors associated with detrusor overactivity in urinary incontinence patients with Alzheimer's disease, and to determine the correlation between the degree of Alzheimer's disease and the presence of detrusor overactivity. METHODS: A total of 144 Alzheimer's disease patients (48 men, 96 women; aged 56-97 years) with urinary incontinence were enrolled in this protocol. Cognitive testing was carried out using the Mini-Mental State Examination, the Clinical Dementia Rating scale, the Global Deterioration Scale and Barthel's Activities of Daily Living. Urinary incontinence was assessed using a frequency-volume chart and the Incontinence Questionnaire on Urinary Incontinence Short Form. All study participants had a urodynamic study carried out. RESULTS: Based on the Incontinence Questionnaire on Urinary Incontinence Short Form, the most common type of urinary incontinence was urge urinary incontinence followed by enuresis in men, whereas women most commonly complained of urge urinary incontinence followed by stress urinary incontinence. Detrusor overactivity was found in 57.6% of patients (25 men, 58 women) on urodynamic study. No statistical differences were found between those with and without detrusor overactivity in terms of age, sex or duration of education. No significant correlation was found between changes in Incontinence Questionnaire on Urinary Incontinence Short Form scores and those in the Mini-Mental State Examination, Clinical Dementia Rating and Barthel's Activities of Daily Living status. Multiple logistic regression analysis showed the presence of detrusor overactivity could be predicted using Clinical Dementia Rating and Barthel's Activities of Daily Living scores (P < 0.05). CONCLUSIONS: The most common type of urinary incontinence in patients with Alzheimer's disease is urge urinary incontinence. Clinical Dementia Rating and Barthel's Activities of Daily Living predict the severity of detrusor overactivity in this patient population.

Increased carotid intima-media thickness and plasma homocysteine levels predict cardiovascular and all-cause death: a population-based cohort study.

BACKGROUND: There is still debate over the utility of carotid intima-media thickness (C-IMT) or carotid plaque in predicting future cardiovascular events and death. Additionally, the importance of plasma homocysteine levels was raised as a predictor of cardiovascular events and death. METHODS: 1,391 subjects were recruited from the Ansan Geriatric cohort. We used B-mode carotid ultrasonography to assess C-IMT and plaque, measuring average maximal IMT and average mean IMT through 6-8 measurements of far-wall IMT in both common carotid arteries. We evaluated the presence of plaque in carotid segments. Multivariable Cox regression analysis was used to predict both cardiovascular and all-cause mortality. RESULTS: During a mean follow-up of 62.4 ± 12.4 months, 71 subjects (5.12%) died and 23 (1.66%) died of cardiovascular causes. Multivariable Cox regression analysis found the predictors of cardiovascular mortality to be average maximal IMT (HR = 3.709; 95% CI: 1.202-11.446) and plasma homocysteine (HR = 1.057; 95% CI: 1.012-1.103). All-cause mortality was independently associated with C-IMT (average maximal and average mean IMT) and plasma homocysteine. CONCLUSIONS: C-IMT and plasma homocysteine levels were found to predict cardiovascular and all-cause mortality independently of the presence of carotid plaque and other cardiovascular risk factors.

Plasminogen Activator Inhibitor-1: Potential Inflammatory Marker in Late-life Depression.

Objective: Although several previous studies have examined the association between late-life depression and blood adipokine levels, a marker of chronic inflammation, no studies have comprehensively considered the effects of metabolic syndrome, which is known to affect blood adipokine levels. This study examined blood adipokine levels in geriatric depression after adjusting for the effects of metabolic syndrome. Methods: Participants were selected from the Ansan Geriatric Study (depression group [n = 76] and control group [n = 76]). Blood concentrations of four adipokines (adiponectin, resistin, neutrophil-gelatinase-associated lipocalin [NGAL], and plasminogen activator inhibitor-1 [PAI-1]) were measured using immunoassays. The effects of blood adipokine concentration on the diagnosis of depression were analyzed using multivariate logistic regression to adjust for the effects of metabolic syndrome and potential confounding factors. Results: When the effects of metabolic syndrome and potential confounding factors were adjusted, only PAI-1 could explain the diagnosis of depression among all the adipokines. The depression group showed a lower blood PAI-1 level than the control group. Adiponectin, resistin, and NGAL could not explain the diagnosis of depression when the effects of metabolic syndrome and potential confounding factors were adjusted. Conclusion: This study suggests the possibility that the blood PAI-1 levels in clinically pathological late-life depression may show contrasting results to those with subclinical depressive symptoms. Additionally, considering that most previous studies have been conducted with pre-geriatric populations, the study suggests the possibility that geriatric depression may show inflammatory changes with patterns that are different from those of depression in the pre-geriatric population.

DNA methylation of the 5'-untranslated region at +298 and +351 represses BACE1 expression in mouse BV-2 microglial cells.

BACE1, which cleaves the amyloid precursor protein, is the rate-limiting enzyme for ß-amyloid peptide production, leading to the pathogenesis of Alzheimer's disease (AD). A high plasma level of homocysteine, acting as a potent methyltransferase inhibitor, is assumed to be a risk factor for AD onset. Using the demethylating drug 5-aza-2'-deoxycytidine (5-Aza), we tested whether and how BACE1 expression is regulated in mouse BV-2 microglial cells. 5-Aza increased both BACE1 mRNA and protein levels in a dose-dependent manner. Bisulfite-sequencing analysis revealed that two CpG sites at positions +298 and +351 in the 5'-untranslated region (5'-UTR) of the BACE1 gene were specifically demethylated in BV-2 cells treated with 5-Aza. In silico analysis showed that the +351 site is the STAT3/CTCF-binding site; the function of the +298 site has not been identified. To assess whether these two CpG sites play an important role in 5-Aza-induced transcriptional activation of BACE1, we constructed a BACE1 gene promoter including the 5'-UTR (-1136 to +500) fused to a CpG-free luciferase gene (pCpGL-BACE1) and its mutant pCpGL-BACE1-AA, which has substituted CG dinucleotides at the two CpG sites of pCpGL-BACE1 to AA. Promoter analysis showed a significant decrease (∼30%) in the activity of pCpGL-BACE1-AA compared with that of pCpGL-BACE1. Furthermore, in vitro methylation of these two reporter constructs showed a complete silencing of their promoter activities. Our data demonstrate that BACE1 gene expression is regulated by DNA methylation of at least two CpG sites at positions +298 and +351 in the 5'-UTR in BV-2 microglial cells.

Influence of BDNF variants on diagnosis and response to treatment in patients with major depression, bipolar disorder and schizophrenia.

AIM: The present study aimed to explore whether some single nucleotide polymorphisms (SNPs) within the BDNF gene could be associated with major depression (MD), bipolar disorder (BD) and schizophrenia, and whether they could predict clinical outcomes in Korean inpatients treated with antidepressants, mood stabilizers and antipsychotics, respectively. METHODS: One hundred and forty-five patients with MD, 132 patients with BD, 221 patients with schizophrenia and 170 psychiatrically healthy controls were genotyped for 5 BDNF SNPs (rs2030324, rs7103873, rs10835210, rs11030101 and rs6265). Baseline and final clinical measures--including the Montgomery-Asberg Depression Rating Scale, Young Mania Rating Scale and Positive and Negative Symptoms Scale for patients with MD, BD and schizophrenia, respectively--were recorded. RESULTS: rs10835210 CA and rs11030101 AT genotype frequencies were higher in BD and schizophrenia patients than in healthy and MD subjects. No significant association was found with clinical improvement. DISCUSSION: Our findings provide evidence of an association between BDNF and BD and schizophrenia. However, taking into account the several limitations of our study, including the moderately small sample size, further research is needed to draw more definitive conclusions.

Influence of GRIA1, GRIA2 and GRIA4 polymorphisms on diagnosis and response to treatment in patients with major depressive disorder.

The present study is aimed to exploring whether some single nucleotide polymorphisms (SNPs) within GRIA1, GRIA2 and GRIA4 could be associated with major depressive disorder (MDD) and whether they could predict clinical outcomes in Korean in-patients, respectively, treated with antidepressants. One hundred forty-five (145) patients with MDD and 170 healthy controls were genotyped for 17 SNPs within GRIA1, GRIA2 and GRIA4. Baseline and final clinical measures, including the Montgomery-Asberg Depression Rating Scale (MADRS) for patients with MDD, were recorded. No association was observed between alleles, genotypes and haplotypes under investigation and clinical and demographical variables. As a secondary finding, a marginal association was observed between rs4302506 and rs4403097 alleles within GRIA2 and age of onset in patients with MDD. Our findings provide evidence for a possible association between rs4302506 and rs4403097 SNPs and age of onset in patients with MDD. However, taking into account that the several limitations of our study including the moderately small sample size of our study, our findings should be considered with caution and further research is needed to draw more definitive conclusions.