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Chronic Fluoxetine Induces Activity Changes in Recovery From Poststroke Anxiety, Depression, and Cognitive Impairment.

ABSTRACT: Poststroke depression (PSD) is a common outcome of stroke that limits recovery and is only partially responsive to chronic antidepressant treatment. In order to elucidate changes in the cortical-limbic circuitry associated with PSD and its treatment, we examined a novel mouse model of persistent PSD. Focal endothelin-1-induced ischemia of the left medial prefrontal cortex (mPFC) in male C57BL6 mice resulted in a chronic anxiety and depression phenotype. Here, we show severe cognitive impairment in spatial learning and memory in the stroke mice. The behavioral and cognitive phenotypes were reversed by chronic (4-week) treatment with fluoxetine, alone or with voluntary exercise (free-running wheel), but not by exercise alone. To assess chronic cellular activation, FosB+ cells were co-labeled for markers of glutamate/pyramidal (VGluT1-3/CaMKII?), ?-aminobutyric acid (GAD67), and serotonin (TPH). At 6 weeks poststroke versus sham (or 4 days poststroke), left mPFC stroke induced widespread FosB activation, more on the right (contralesional) than on the left side. Stroke activated glutamate cells of the mPFC, nucleus accumbens, amygdala, hippocampus, and raphe serotonin neurons. Chronic fluoxetine balanced bilateral neuronal activity, reducing total FosB and FosB/CamKII+ cells (mPFC, nucleus accumbens), and unlike exercise, increasing FosB/GAD67+ cells (septum, amygdala) or both (hippocampus, raphe). In summary, chronic antidepressant but not exercise mediates recovery in this unilateral ischemic PSD model that is associated with region-specific reversal of stroke-induced pyramidal cell hyperactivity and increase in ?-aminobutyric acidergic activity. Targeted brain stimulation to restore brain activity could provide a rational approach for treating clinical PSD.

SUBMITTER: Vahid-Ansari F

PROVIDER: S-EPMC5794702 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Chronic Fluoxetine Induces Activity Changes in Recovery From Poststroke Anxiety, Depression, and Cognitive Impairment.

Vahid-Ansari Faranak F Albert Paul R PR

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20180101 1

Poststroke depression (PSD) is a common outcome of stroke that limits recovery and is only partially responsive to chronic antidepressant treatment. In order to elucidate changes in the cortical-limbic circuitry associated with PSD and its treatment, we examined a novel mouse model of persistent PSD. Focal endothelin-1-induced ischemia of the left medial prefrontal cortex (mPFC) in male C57BL6 mice resulted in a chronic anxiety and depression phenotype. Here, we show severe cognitive impairment ...[more]

PMID: 29204954

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Project description:OBJECTIVE:To determine if pretreatment nonlinguistic cognition predicted language treatment outcomes and if so, which specific nonlinguistic cognitive subskills predicted naming therapy outcomes. DESIGN:Retrospective. SETTING:Research clinic. PARTICIPANTS:Study 1 included data from 67 persons with aphasia who underwent language treatment and a pretreatment cognitive-linguistic assessment battery (N=67). Study 2 included data from 27 study 1 participants who completed additional pretreatment nonlinguistic cognitive assessments. INTERVENTIONS:120-minute sessions of sentence comprehension (n=26) or naming treatment (n=41) 2 times per week for up to 10-12 weeks. MAIN OUTCOME MEASURES:Proportion of potential maximal gain (PMG) (assessed immediately after treatment [10-12wk]; formula=mean posttreatment score-mean pretreatment score/total number of trained items-mean pretreatment score) and proportion of potential maximal gain maintained (PMGM) (assessed 12wk after posttreatment [22-24wk]; formula=mean maintenance score-mean pretreatment score/total number of trained items-mean pretreatment score) as outcome variables; and pretreatment assessment scores as predictor variables. RESULTS:In study 1, 37% of participants demonstrated nonlinguistic cognitive deficits. Principal component analyses reduced assessment data to 2 components: linguistic and nonlinguistic cognition. Backward elimination regression revealed that higher linguistic and nonlinguistic cognitive function significantly predicted higher PMG after language therapy. In study 2, principal component analysis of only the nonlinguistic cognitive measures identified 3 components: executive function, verbal short-term memory, and visual short-term memory. Controlling for pretreatment apraxia of speech and auditory comprehension deficits, regression analyses revealed that higher executive function and visual short-term memory significantly predicted higher PMG and PMGM after naming therapy. CONCLUSIONS:Pretreatment nonlinguistic cognitive function significantly influenced language treatment outcomes and maintenance of therapy gains.

Project description:Background: Poststroke cognitive impairment (PSCI) has been increasingly recognized in patients, but some stroke survivors appear to show cognitive improvement beyond the acute stage. The risk factors associated with cognitive recovery after spontaneous intracerebral hemorrhage (ICH) onset have not yet been sufficiently investigated in prospective studies. Objective: We aimed to identify the trajectory of post-ICH cognitive impairment and the association of potential prognostic factors with follow-up cognitive recovery beyond early PSCI. Methods: In this stroke center-based cohort study, 141 consecutive dementia-free patients with spontaneous ICH were included and underwent Montreal Cognitive Assessment (MoCA) evaluation for cognitive function at baseline (within 2 weeks of ICH onset) and the shortened MoCA (short-MoCA) at a 6-month follow-up. To explore the prognostic factors associated with trajectory of cognition after an ICH onset, we adjusted for demographic and vascular risk factors, using multivariate logistic regression analysis. Results: Of the 141 ICH patients, approximately three quarters (106/141) were diagnosed with early PSCI (MoCA score <26) within 2 weeks of ICH onset. The multiple logistic regression indicated independent positive associations between risk of early PSCI and dominant-hemisphere hemorrhage [odd's ratio (OR): 8.845 (3.347-23.371); P < 0.001], mean corpuscular volume (MCV) [OR: 1.079 (1.002-1.162); P = 0.043], admission systolic blood pressure (sBP) [OR: 1.021 (1.005-1.038); P = 0.012]. Furthermore, 36% (33/90) of ICH survivors who had early PSCI exhibited cognitive recovery at the 6-month follow-up. After examining potential predictors through multiple linear regression based on stepwise, there were independent negative associations between cognitive recovery and dominant hemisphere hemorrhage [OR: 6.955 (1.604-30.162); P < 0.01], lobar ICH [OR: 8.363 (1.479-47.290); P = 0.016], years of education ? 9 [OR: 5.145 (1.254-21.105); P = 0.023], and MCV [OR: 1.660 (1.171-2.354); P = 0.004]. Baseline cognitive performance in the domains of visuospatial/executive function, attention, orientation, and language showed positive correlations with cognitive improvement (P < 0.05). Conclusion: In this cohort study of dementia-free survivors of ICH, our results show that one in three early PSCI survivors exhibit cognitive recovery, in relation to dominant-hemisphere hematoma, lobar ICH, educational history, and MCV levels. Future clinical trials including ICH survivors with cognitive dysfunction should assess these factors.

Project description:BackgroundExperiencing anxiety and depression is very common in people with dementia and mild cognitive impairment (MCI). Psychological interventions have been suggested as a potential treatment for these populations. Current research suggests that people with dementia and MCI have limited opportunities for psychological treatments aimed at improving their well-being. A systematic review of the evidence on their effectiveness is likely to be useful in terms of improving outcomes for patients and for future recommendations for practice.ObjectivesThe main objective of this review was to assess the effectiveness of psychological interventions in reducing anxiety and depression in people with dementia or mild cognitive impairment (MCI).Search methodsWe searched the Cochrane Dementia and Cognitive Improvement Group Specialized Register and additional sources for both published and unpublished data.Selection criteriaWe included randomised controlled trials (RCTs) comparing a psychological intervention with usual care or a placebo intervention (social contact control) in people with dementia or MCI.Data collection and analysisTwo review authors worked independently to select trials, extract data and assess studies for risk of bias, using a data extraction form. We contacted authors when further information was not available from the published articles.Main resultsSix RCTs involving 439 participants with dementia were included in the review, but no studies of participants with MCI were identified. The studies included people with dementia living in the community or in nursing home care and were carried out in several countries. Only one of the studies was classified as low risk of bias. Five studies were at unclear or high risk of bias due to uncertainties around randomisation, blinding and selective reporting of results. The studies used the different psychological approaches of cognitive behavioural therapy (CBT), interpersonal therapy and counselling. Two studies were of multimodal interventions including a specific psychological therapy. The comparison groups received either usual care, attention-control educational programs, diagnostic feedback or services slightly above usual care.Meta-analysis showed a positive effect of psychological treatments on depression (6 trials, 439 participants, standardised mean difference (SMD) -0.22; 95% confidence interval (CI) -0.41 to -0.03, moderate quality evidence) and on clinician-rated anxiety (2 trials, 65 participants, mean difference (MD) -4.57; 95% CI -7.81 to -1.32, low quality evidence), but not on self-rated anxiety (2 trials, SMD 0.05; 95% CI -0.44 to 0.54) or carer-rated anxiety (1 trial, MD -2.40; 95% CI -4.96 to 0.16). Results were compatible with both benefit and harm on the secondary outcomes of patient quality of life, activities of daily living (ADLs), neuropsychiatric symptoms and cognition, or on carers' self-rated depressive symptoms, but most of the studies did not measure these outcomes. There were no reports of adverse events.Authors' conclusionsWe found evidence that psychological interventions added to usual care can reduce symptoms of depression and clinician-rated anxiety for people with dementia. We conclude that psychological interventions have the potential to improve patient well-being. Further high quality studies are needed to investigate which treatments are most effective and to evaluate the effect of psychological interventions in people with MCI.

Dataset Information

Chronic Fluoxetine Induces Activity Changes in Recovery From Poststroke Anxiety, Depression, and Cognitive Impairment.

Publications

Chronic Fluoxetine Induces Activity Changes in Recovery From Poststroke Anxiety, Depression, and Cognitive Impairment.

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