Effects of Vitamin D Supplementation on Cognitive Outcomes: A Systematic Review and Meta-Analysis.

Clinical studies examining the effects of vitamin D on cognition have reported inconsistent results. To date, no comprehensive study has examined this effect on the basis of sample characteristics or intervention model-related factors. This systematic review and meta-analysis of randomized controlled trials investigated the effects of vitamin D supplementation on global cognitive function and specific cognitive domains. This review was preregistered in the PROSPERO database (CRD42021249908) and comprised 24 trials enrolling 7557 participants (mean age: 65.21 years; 78.54% women). The meta-analysis revealed that vitamin D significantly influenced global cognition (Hedges' g = 0.128, p = .008) but not specific cognitive domains. A subgroup analysis indicated that the effect size of vitamin D was stronger for vulnerable populations (Hedges' g = 0.414) and those with baseline vitamin D deficiency (Hedges' g = 0.480). On the basis of subgroup analyses in studies without biological flaws (Hedges' g = 0.549), we suggest that an intervention model should correct baseline vitamin D deficiency. Our results indicate that vitamin D supplementation has a small but significant positive effect on cognition in adults.

Incidence, risk and protective factors for suicide mortality among patients with major depressive disorder.

AIM: Patients with major depression have greater suicide mortality, but there is no data on the standardised mortality ratio (SMR) and factors for suicide of major depression for Asian countries. This research estimates the SMR and the risk and protective factors for suicide mortality in patients with major depression in a large-scale Asian cohort. METHODS: Patients with major depression (N = 1978) admitted to a psychiatric hospital in Taiwan between 1985 and 2008 were enrolled as the study cohort. When the cohort was linked to the national mortality database, 415 deceased patients were identified. Of these 415 deaths, 107 were from suicide. Nested case-control with risk sampling was used, where each case was matched with two controls. Clinical information was collected through a standardised chart review process. The SMR for suicide mortality was estimated, and a conditional logistic regression analysis was performed to determine risk and protective factors for suicide. RESULTS: Patients with major depression had high all-cause and suicide mortality, with SMRs of 3.9 and 35.4, respectively. Agitation (adjusted risk ratio [aRR] = 2.85, P = 0.058), restlessness (aRR = 15.05, P = 0.045) and previous suicide attempts (aRR = 4.48, P = 0.004) were identified as risk factors for suicide mortality. By contrast, those with employment (aRR = 0.15, P = 0.003) or loss of interest (aRR = 0.32, P = 0.04) had lower risk. CONCLUSIONS: Patients with depression exhibited higher suicide mortality. Clinical staff should pay close attention to risk and protective factors to reduce suicide risk.

Effect of Pharmacological and Neurostimulation Interventions for Cognitive Domains in Patients with Bipolar Disorder: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: The priority of interventions to alleviate cognitive deficits in patients with bipolar disorder (BD) is inconclusive. We systematically evaluate the efficacy of pharmacological or neurostimulation interventions for cognitive function in BD through a network meta-analysis. METHODS: The PubMed, PsycINFO, Embase, and Cochrane Library databases were searched from database inception to September 30, 2021. Following PRISMA guidelines, all eligible studies were randomized controlled trials of adult bipolar patients that provided detailed cognitive outcomes. Studies were excluded if participants limited to comorbid substance use disorder or the intervention was a psychotherapy. Network meta-analysis comparing different interventions was conducted for 8 cognitive domains. Partially ordered set with Hasse diagram was used to resolve conflicting rankings between outcomes. The study was preregistered on PROSPERO database (CRD42020152044). RESULTS: Total 21 RCTs including 42 tests for assessing intervention effects on cognition were retrieved. Adjunctive erythropoietin (SMD = 0.61, 95% CI = 0.00-1.23), Withania somnifera (SMD = 0.58, 95% CI = 0.03-1.13), and galantamine (SMD = 1.22, 95% CI = 0.10-2.35) was more beneficial for attention, working memory, and verbal learning in euthymic BD patients than treatment as usual, respectively. Hasse diagram suggested ranking of choice when multiple domains were combined. CONCLUSION: Considerable variability in measurements of cognitive domains in BD was observed, and no intervention resulted in superior benefits across all domains. We suggested interventions priority can be tailored according to individual patients' cognitive deficits. As current findings from relatively small and heterogeneous dataset, future trials with consensus should be applied for building further evidence.

Shortened leukocyte telomere length in young adults who use methamphetamine.

Methamphetamine (METH) use, most prevalent in young adults, has been associated with high rates of morbidity and mortality. The relationship between METH use and accelerated biological aging, which can be measured using leukocyte telomere length (LTL), remains unclear. We examined whether young adult METH users have shorter LTL and explored the relationship between characteristics of METH use and LTL by using Mendelian randomization (MR) analysis. We compared the LTL for 187 METH users and 159 healthy individuals aged between 25 and 34 years and examined the relationship of LTL with METH use variables (onset age, duration, and maximum frequency of METH use) by using regression analyses. In addition, 2-stage-least-squares (2SLS) MR was also performed to possibly avoid uncontrolled confounding between characteristics of METH use and LTL. We found METH users had significantly shorter LTL compared to controls. Multivariate regression analysis showed METH use was negatively associated with LTL (ß = -0.36, P < .001). Among METH users, duration of METH use was negatively associated with LTL after adjustment (ß = -0.002, P = .01). We identified a single nucleotide polymorphism (SNP) rs6585206 genome-wide associated with duration of METH use. This SNP was used as an instrumental variable to avoid uncontrolled confounding for the relationship between the use duration and LTL shortening. In conclusion, we show that young adult METH users may have shorter LTL compared with controls and longer duration of METH use was significantly associated with telomere shortening. These observations suggest that METH use may accelerate biological senescence.

The Heterogeneity of Longitudinal Cognitive Decline in Euthymic Bipolar I Disorder With Clinical Characteristics and Functional Outcomes.

We characterized the heterogeneity and risk factors of cognitive decline in euthymic bipolar disorder (BD), and their magnitude of associations with subjective daily functions. In this retrospective cohort, BD type I patients (N = 128) were followed for an average of 6.5 years. Intelligence quotient (IQ) at index date was recorded, and premorbid IQ was estimated. We used Brief Assessment of Cognition in Affective Disorders (BAC-A) to assess cognition at follow-up. We evaluated current functions with World Health Organization Disability Assessment Schedule 2.0. Clinical and sociodemographic factors were examined for their independent effects on longitudinal cognitive decline. In addition, we employed multivariate adaptive regression spline to detect inflection points for the nature of slope changes in cognitive decline among BD patients. During follow-up years, 21 BD patients (16.4%) showed longitudinal cognitive decline. In cognitive decline group, all cognitive domains of BAC-A were significantly worsened. We found that density of episodes with psychotic features was an independent risk factor for cognitive decline after adjusted for age, gender and dose of mood stabilizer. After the age of 42 years, a steeper cognitive change was observed in the cognitive decline group. The correlation pattern between cognitive domains and functional outcomes differed between patients with and without cognitive decline. The present study characterized cognitive heterogeneity longitudinally in BD patients. As density of episodes play roles for cognitive decline, our results emphasize the importance of relapse prevention. Our findings provide hints for future personalized interventions and facilitating genetic and biological studies for dissecting the heterogeneity of bipolar illness.

Exploring the mediating role of methamphetamine use in the relationship between adverse childhood experiences and attempted suicide.

OBJECTIVE: Methamphetamine (METH) use and adverse childhood experiences (ACEs) has been associated with an increased risk of suicidal behaviour. However, whether METH use underlies the risk of suicide attributable to ACEs is unknown and warrants investigation to inform preventive interventions. In this study, we examined the mediating role of METH use in the relationship between attempted suicide and ACEs. METHOD: METH users recruited from a mandatory detoxification center (n = 346) and healthy controls (n = 342) both completed a survey related to 9 types of ACE, which was based the Family Health Questionnaire. A lifetime history of attempted suicide was obtained using the Chinese version of the Composite International Diagnostic Interview. We conducted a bootstrapped mediation analysis to examine the mediating effect of METH use on the association between ACEs and attempted suicide. RESULTS: Female gender, METH use, and having multiple (≥3) ACEs were associated with an increased risk of attempted suicide. A dose-response relationship between the number of ACEs and suicide rate was observed among individuals with METH use. METH use significantly mediated the association between ACEs and attempted suicide in those with multiple (2 and 3 ACEs respectively with proportion mediated 0.16 and 0.42) and specific types of ACEs (physical abuse, witnessing maternal battering, household substance abuse, sexual abuse, and parental separation with proportion mediated 0.25, 0.35, 0.38, 0.48, 0.47 respectively). CONCLUSION: Our study is the first to demonstrate that METH use partially mediates the association between ACEs and attempted suicide. Addressing METH use in people with ACEs could reduce their suicide risk.

Palliative care for nursing home patients with dementia: service evaluation and risk factors of mortality.

BACKGROUND: Difficulties in prognostication are common deterrents to palliative care among dementia patients. This study aimed to evaluate the effectiveness of palliative care in reducing the extent of utilization of medical services and the potential risk factors of mortality among dementia patients receiving palliative care. METHODS: We surveyed dementia patients involved in a palliative care program at a long-term care facility in Taipei, Taiwan. We enrolled 57 patients with advanced dementia (clinical dementia rating ≥ 5 or functional assessment staging test stage 7b). We then compared the extent of their utilization of medical services before and after the provision of palliative care. Based on multivariable logistic regression, we identified potential risk factors before and after the provision of palliative care associated with 6-month mortality. RESULTS: The utilization of medical services was significantly lower among dementia patients after the provision of palliative care than before, including visits to medical departments (p < 0.001), medications prescribed (p < 0.001), frequency of hospitalization (p < 0.001), and visits to the emergency room (p < 0.001). Moreover, patients dying within 6 months after the palliative care program had a slightly but not significantly higher number of admissions before receiving hospice care (p = 0.058) on univariate analysis. However, no significant differences were observed in multivariate analysis. CONCLUSIONS: The provision of palliative care to dementia patients reduces the extent of utilization of medical services. However, further studies with larger patient cohorts are required to stratify the potential risk factors of mortality in this patient group.

Comparison of cognitive function between early- and late-onset late-life depression in remission.

Differences in cognitive function have been suggested in people with late-life depression between those with early- (EOD) and late-onset (LOD), possibly reflecting different etiologies. The cutoff point for EOD and LOD was the first depressive episode before age 60 or later. However, depressive symptoms at the time of disorder are important confounders. The study aimed to compare cognitive function in older people with EOD and LOD in the euthymic state. A sample of 135 participants aged 60+ with a history of major depressive disorder in remission, received neuropsychological evaluation including tests of memory, attention, processing speed, visuospatial function, language, and executive function. Individual test scores and a derived composite score were investigated as dependent variables against age of onset using multiple linear regressions adjusted for potential confounders, including residual depressive symptoms. We found EOD (N = 67) and LOD (N = 68) groups did not differ significantly in overall composite cognitive scores after adjustment. Of individual test scores, only those for immediate recall were significantly lower in participants with EOD compared to LOD. In conclusion, the study found no associations between cognitive function and age of onset in this sample of people with depressive disorder in remission. Active or residual depressive symptoms might have confounded this relationship in previous research.

The updated PIM-Taiwan criteria: a list of potentially inappropriate medications in older people.

BACKGROUND: Explicit criteria for potentially inappropriate medications (PIMs) developed for other countries are difficult to apply to a specific territory. This study aimed to update the PIM-Taiwan criteria from a qualitative review of several published PIM criteria, followed by consensus among regional experts in Taiwan. METHODS: After a review of the literature, we selected four sets of published PIM criteria to construct preliminary core PIMs. The Beers criteria, Fit fOR The Aged (FORTA), and Japan criteria were used for PIMs, without consideration of chronic diseases. The Beers criteria, Screening Tool of Older Persons' Prescriptions (STOPP) criteria, and Japan criteria were used for PIMs with respect to chronic diseases. We asked experts (n = 24) to rate their agreement with each statement, including in the final PIM criteria, after two rounds of modified Delphi methods. The intraclass coefficient (ICC) was used to examine the reliability of the modified Delphi method. RESULTS: Overall, two categories of PIMs were established: 131 individual drugs and 9 drugs with combinations that should generally be avoided; and 9 chronic diseases with their corresponding PIMs that have drug-disease interactions. The ICC estimates for PIMs to be avoided generally were 0.634 and 0.557 (round 1 and 2) and those for PIMs with respect to chronic diseases were 0.866 and 0.775 (round 1 and 2) of the Delphi method, respectively. CONCLUSIONS: The 2018 version of PIM-Taiwan criteria was established and several modifications were made to keep the criteria updated and relevant. Clinicians can use them to reduce polypharmacy and PIMs among older patients.

Homocysteine, rather than age of onset, is a better predictor for cognitive function in older adults with bipolar disorder.

OBJECTIVES: The association between older-age bipolar disorder and cognitive impairments may be mediated by vascular burden. The aim of the study was to examine the difference of cognitive function between older people with late-onset bipolar disorder (LOBD) and early-onset bipolar disorder (EOBD) by considering rigorous vascular risk burden evaluation, comprehensive cognitive tests, and relevant biochemistry data. METHODS: We recruited 95 outpatients aged over 55 with a DSM-IV-TR diagnosis of bipolar I disorder. Fifty had LOBD, defined by age of onset after 40. Cognitive function was evaluated through a battery of tests assessing verbal memory, attention/speed, visuospatial function, verbal fluency, and cognitive flexibility. Vascular risk assessments included individual disorders, 10-year Framingham cardiovascular risk scores, and serum levels of homocysteine, vitamin B12, folate, and triiodothyronine. RESULTS: No differences were observed between LOBD and EOBD on any cognitive test after adjusting for potential confounders. In addition to age and educational years, multiple linear regression analyses indicated significantly negative associations between serum homocysteine levels and cognitive performances in attention, psychomotor speed, verbal memory, and executive function. CONCLUSIONS: Among older people with bipolar disorder, LOBD is not associated with more cognitive dysfunction in this study. However, higher serum homocysteine levels were significantly associated with worse cognitive performance in this particular group. Clinicians therefore have to pay attention to the cognitive function in older bipolar patients with higher levels of homocysteine.

Correction: Antipsychotic medications and stroke in schizophrenia: A case-crossover study.

[This corrects the article DOI: 10.1371/journal.pone.0179424.].

The application of updating PIM-Taiwan criteria in clinic-visiting older patients with polypharmacy.

BACKGROUND: PIM-Taiwan criteria were first established in 2010 for potentially inappropriate medications (PIMs). Currently, updating of PIM criteria is mandatory because of newly established evidence and newly developed medications. This study aims to evaluate the prevalence of PIM based on country-specific PIM criteria and factors associated with PIM use by applying 2010 version and newly updating PIM-Taiwan criteria in a cohort with polypharmacy. METHODS: The baseline data of Medication Safety Review Clinic Taiwan (MSRC-Taiwan) study were used to investigate the prevalence of PIMs. Older patients (aged ⩾65 years) who were either having polypharmacy or visited ⩾3 different physicians were enrolled between August and October 2007. Bivariate analysis and multivariate logistic regressions were used to evaluate the factors associated with PIM use. RESULTS: The prevalence of having at least one PIM was 46.1% for 2010 version and increased to 74.6% for 2018 version. The average number of PIMs generally to be avoided per patient also increased for 2018 version (0.2 versus 1.2, p < 0.0001). In contrast, the average number of PIMs considering chronic conditions per patient decreased (0.6 versus 0.3, p < 0.001). The associated chronic conditions of PIM users were distinct between 2010 and 2018 version. The major leading PIMs were benzodiazepines (BZDs) in both versions of criteria. CONCLUSIONS: As there were significant differences in medication lists between PIM-Taiwan version 2010 and 2018, the prevalence of PIM and factors associated with PIM users varied accordingly. Physicians should pay special attention before prescribing BZDs which keep being the major leading PIM.

Benzodiazepines and risk of pneumonia in schizophrenia: a nationwide case-control study.

OBJECTIVES: To investigate the relationship between benzodiazepine and risk of developing pneumonia in patients with schizophrenia, whose benzodiazepine dosage and usage frequency was higher than that of the general population. METHODS: We conducted a nested case-control study to assess the association between benzodiazepine use and pneumonia among patients with schizophrenia. By using the Taiwan National Health Insurance Research Database, we identified a schizophrenia cohort comprising 34,929 patients during 2000-2010. Within the schizophrenia cohort, 2501 cases of pneumonia and 9961 matched control patients (1:4 ratio) were identified. Benzodiazepine exposure was categorized by drug, treatment duration, and daily dose. Conditional logistic regression models were used to examine the association between benzodiazepine exposure and the risk of pneumonia. RESULTS: The current use (within 30 days) of midazolam led to the highest pneumonia risk (adjusted risk ratio = 6.56, P < 0.001), followed by diazepam (3.43, P < 0.001), lorazepam (2.16, P < 0.001), and triazolam (1.80, P = 0.019). Furthermore, nearly all the benzodiazepines under current use had a dose-dependent effect on pneumonia risk. The risk of pneumonia was correlated with the affinities of γ-aminobutyric acid A α1, α2, and α3 receptors. CONCLUSIONS: Benzodiazepines had a dose-dependent relationship with pneumonia in patients with schizophrenia. The differences in risk and mechanism of action of the individual drugs require further investigation. Clinicians should be aware of the early signs of pneumonia in patients with schizophrenia receiving benzodiazepines.

Prescription of potentially inappropriate medication to older patients presenting to the emergency department: a nationally representative population study.

Potentially inappropriate medication (PIM) was associated with adverse clinical outcomes and higher healthcare resource utilization among older patients. In order to investigate the prevalence of PIM use based on three different sets of criteria and their associated factors among older patients in the emergency department (ED) in Taiwan. The National Health Insurance Research Database was used for this cross-sectional study. Older patients who visited the ED at least once in 2009 were enrolled. PIMs were identified based on the Beers Criteria, PIM-Taiwan criteria, and PRISCUS criteria. Average patient age was 76.7 ± 7.4 years and patients visited the ED 1.8 ± 2.1 times in 2009. The prevalence and frequency of being prescribed at least one PIM at each visit were high according to all three sets of criteria. Performance of the PIM-Taiwan criteria was only inferior to that of the Beers Criteria. The most important factor associated with PIM was the number of medications prescribed in the ED, and PIM use was associated with higher annual health resource utilization in the ED. PIM use was a significant issue and was associated with higher annual emergency care resource utilization in the ED.

Effect of Apolipoprotein E ɛ4 Carrier Status on Cognitive Response to Acetylcholinesterase Inhibitors in Patients with Alzheimer's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: The apolipoprotein E ɛ4 (APOE ɛ4) genotype is the major genetic risk factor for Alzheimer's disease (AD). However, its effect on an individual's response to treatment is less well understood. Many studies have reported that the presence or absence of APOE ɛ4 may have influence on the therapeutic response for acetylcholinesterase inhibitors (AChEIs), but the results were inconsistent. This study performed a systematic review and meta-analysis to evaluate the association between response of treatment with AChEIs and the APOE ɛ4 carrier status. METHODS: Clinical studies with AD patients reporting APOE ɛ4 genotype were included in the analysis. Cognitive outcome was measured by the change in Mini-Mental State Examination (MMSE), cognition subscales of the Alzheimer's Disease Assessment Scale (ADAS-cog), or Cognitive Abilities Screening Instrument (CASI). A random effects model was employed to calculate the standardized mean difference (SMD) and odds ratio (OR). RESULTS: Of the 284 screened abstracts, 38 studies were identified, 30 of which were included for meta-analysis. Continuous data for assessing the association between APOE ε4 and cognitive outcomes of AChEIs were available from 18 studies. The cognitive outcomes showed no significant difference between APOE ε4 carriers and APOE ε4 non-carriers (SMD = 0.022, 95% CI: -0.089∼0.133, p = 0.702, I2 = 55.3%). Twelve studies with binary data were included, also revealing insignificant difference between the two groups (OR = 1.164, 95% CI: 0.928∼1.459, p = 0.189, I2 = 16.4%). Subgroup analysis indicated that AChEIs were significantly more effective than placebo in both groups. CONCLUSIONS: APOE ɛ4 carrier status had no significant influence on the treatment response to AChEIs in patients with AD. AChEIs had a positive therapeutic effect compared with placebo regardless of APOE ε4 carrier status.

Antipsychotic drugs and risk of newly diagnosed tuberculosis in schizophrenia.

AIM: Patients with schizophrenia have a higher incidence of tuberculosis than do people in the general population. Information is limited regarding the association between antipsychotic agents and the risk of tuberculosis in patients with schizophrenia. This exploratory study assessed the risk of tuberculosis among patients with schizophrenia on antipsychotic therapy. METHODS: Among a nationwide schizophrenia cohort derived from the National Health Insurance Research Database in Taiwan (n = 32 399), we identified 284 patients who had developed newly diagnosed tuberculosis after their first psychiatric admission. Ten or fewer matched controls were selected randomly from the cohort for each patient based on risk-set sampling. We categorized exposure to antipsychotic medications by type and defined daily dose. Using multivariate methods, we explored individual antipsychotic agents for the risk of tuberculosis and employed a propensity-scoring method in sensitivity analyses to validate any associations. RESULTS: Among the antipsychotic agents studied and after adjustment for covariates, current use of clozapine was the only antipsychotic agent associated with a 63% increased risk of tuberculosis (adjusted risk ratio = 1.63, P = 0.014). In addition, the association did not show a clear dose-dependent relationship. Clozapine combined with other antipsychotic agents showed a potential synergistic risk for tuberculosis (adjusted risk ratio = 2.30, P = 0.044). CONCLUSION: This exploratory study suggests the potential risk of clozapine on the risk of tuberculosis, especially for those on clozapine in combination with other antipsychotics. Future studies are needed to verify the association.

Antipsychotic medications and stroke in schizophrenia: A case-crossover study.

BACKGROUND: The association between antipsychotic use and the risk of stroke in schizophrenic patients is controversial. We sought to study the association in a nationwide cohort with schizophrenia. METHODS: Using a retrospective cohort of patients with schizophrenia (N = 31,976) derived from the Taiwan National Health Insurance Research Database, 802 new-onset cases of stroke were identified within 10 years of follow-up (from 2000 through 2010). We designed a case-crossover study using 14-day windows to explore the risk factors of stroke and the association between antipsychotic drugs and the risk of stroke. We analyzed the risks of individual antipsychotics on various subgroups of stroke including ischemic, hemorrhagic, and other strokes, and the risks based on the antipsychotic receptor-binding profile of each drug. RESULTS: Use of any second-generation antipsychotic was associated with an increased risk of stroke (adjusted risk ratio = 1.45, P = .009) within 14 days while the use of any first-generation antipsychotic was not. Intriguingly, the use of any second-generation antipsychotic was associated with ischemic stroke but not hemorrhagic stroke. The antipsychotic receptor-binding profile analysis showed that the antihistamine 1 receptor was significantly associated with ischemic stroke (adjusted risk ratio = 1.72, P = .037), and the sensitivity analysis based on the 7-day window of exposure validated the association (adjusted risk ratio = 1.87, P = .015). CONCLUSIONS: Use of second-generation antipsychotic drugs appeared to be associated with an increased risk of ischemic stroke in the patients studied, possibly mediated by high affinity for histamine-1 receptor blockade. Further research regarding the underlying biological mechanism and drug safety is suggested.

Delirium Associated With Fluoxetine Discontinuation: A Case Report.

BACKGROUND: Withdrawal symptoms on selective serotonin reuptake inhibitor (SSRI) discontinuation have raised clinical attention increasingly. However, delirium is rarely reported in the SSRI discontinuation syndrome. CASE: We report a case of delirium developing after fluoxetine discontinuation in a 65-year-old female patient with major depressive disorder. She experienced psychotic depression with limited response to treatment of fluoxetine 40 mg/d and quetiapine 100 mg/d for 3 months. After admission, we tapered fluoxetine gradually in 5 days because of its limited effect. However, delirious pictures developed 2 days after we stopped fluoxetine. Three days later, we added back fluoxetine 10 mg/d. Her delirious features gradually improved, and the clinical presentation turned into previous psychotic depression state. We gradually increased the medication to fluoxetine 60 mg/d and olanzapine 20 mg/d in the following 3 weeks. Her psychotic symptoms decreased, and there has been no delirious picture noted thereafter. CONCLUSIONS: Delirium associated with fluoxetine discontinuation is a much rarer complication in SSRI discontinuation syndrome. The symptoms of SSRI discontinuation syndrome may be attributable to a rapid decrease in serotonin availability. In general, the shorter the half-life of any medication, the greater the likelihood patients will experience discontinuation symptoms. Genetic vulnerability might be a potential factor to explain that SSRI discontinuation syndrome also occurred rapidly in people taking long-half-life fluoxetine. The genetic polymorphisms of both pharmacokinetic and pharmacodynamic pathways might be potentially associated with SSRI discontinuation syndrome.

Methionine synthase 2756AA polymorphism is associated with the risk of cognitive impairment in patients with late-life depression.

BACKGROUNDS: Apolipoprotein E epsilon-4 (APOE ε4) allele, methylenetetrahydrofolate reductase (MTHFR C677T), and methionine synthase (MTR A2756G) were tested their associations with cognitive impairment in people with late-life depression (LLD). METHODS: People with LLD were assessed by mini-mental state examination and were examined the distribution of APOE ε4 allele, MTHFR, and MTR polymorphisms. RESULTS: Odds ratio of MTR 2756 AA to MTR 2756 AG and GG genotypes for the risk of cognitive impairment was 5.80 (95% confidence interval = 1.18-28.50; P = 0.03). CONCLUSION: People with LLD carrying MTR2756 AA genotype have higher risk of cognitive impairment than those carrying G allele.