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Effects of Selective Serotonin Reuptake Inhibitors on Depression-Like Behavior in a Laser-Induced Shock Wave Model.

ABSTRACT: Primary blast injury can result in depression-like behavior in the long-term. However, the effects of the selective serotonin reuptake inhibitor (SSRI) on the depression induced by mild blast traumatic brain injury (bTBI) in the long-term remain unclear. We generated a mouse model of mild bTBI using laser-induced shock wave (LISW) and administered an SSRI to mice by oral gavage for 14 days after LISW exposure. This study aimed to investigate the mechanisms of SSRI-mediated alleviation of depression-like behavior induced by mild bTBI. Animals were divided into three groups: sham, LISW-Vehicle, and LISW-SSRI. LISW was applied to the head of anesthetized mice at 0.5 J/cm². Twenty-eight days after the LISW, mice in the LISW-SSRI group exhibited reduced depression-like behavior, a significant increase in the number of cells co-stained for 5-bromo-2'-deoxyuridine (Brd-U) and doublecortin (DCX) in the dentate gyrus (DG) as well as increased brain-derived neurotrophic factor (BDNF) and serotonin levels in the hippocampus compared to the sham and LISW-Vehicle groups. Additionally, levels of phosphorylated cAMP response element binding protein (pCREB) in the DG were significantly decreased in the LISW-Vehicle group compared to that in the sham group. Importantly, pCREB levels were not significantly different between LISW-SSRI and sham groups suggesting that SSRI treatment may limit the downregulation of pCREB induced by mild bTBI. In conclusion, recovery from depression-like behavior after mild bTBI may be mediated by hippocampal neurogenesis induced by increased BDNF and serotonin levels as well as the inhibition of pCREB downregulation in the hippocampus.

SUBMITTER: Seno S

PROVIDER: S-EPMC7902879 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Effects of Selective Serotonin Reuptake Inhibitors on Depression-Like Behavior in a Laser-Induced Shock Wave Model.

Seno Soichiro S Tomura Satoshi S Miyazaki Hiromi H Sato Shunichi S Saitoh Daizoh D

Frontiers in neurology 20210210

Primary blast injury can result in depression-like behavior in the long-term. However, the effects of the selective serotonin reuptake inhibitor (SSRI) on the depression induced by mild blast traumatic brain injury (bTBI) in the long-term remain unclear. We generated a mouse model of mild bTBI using laser-induced shock wave (LISW) and administered an SSRI to mice by oral gavage for 14 days after LISW exposure. This study aimed to investigate the mechanisms of SSRI-mediated alleviation of depress ...[more]

PMID: 33643190

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Project description:The physiology of mood regulation in the postpartum is poorly understood despite the fact that postpartum depression (PPD) is a common pathology. Serotonergic mechanisms and their dysfunction are widely presumed to be involved, which has led us to investigate whether lactation induces changes in central or peripheral serotonin (5-HT) systems and related affective behaviors. Brain sections from lactating (day 10 postpartum) and age-matched nulliparous (non-pregnant) C57BL/6J mice were processed for 5-HT immunohistochemistry. The total number of 5-HT immunostained cells and optical density were measured. Lactating mice exhibited lower immunoreactive 5-HT and intensity in the dorsal raphe nucleus when compared with nulliparous controls. Serum 5-HT was quantified from lactating and nulliparous mice using radioimmunoassay. Serum 5-HT concentrations were higher in lactating mice than in nulliparous controls. Affective behavior was assessed in lactating and non-lactating females ten days postpartum, as well as in nulliparous controls using the forced swim test (FST) and marble burying task (MBT). Animals were treated for the preceding five days with a selective serotonin reuptake inhibitor (SSRI, citalopram, 5mg/kg/day) or vehicle. Lactating mice exhibited a lower baseline immobility time during the FST and buried fewer marbles during the MBT as compared to nulliparous controls. Citalopram treatment changed these behaviors in lactating mice with further reductions in immobility during the FST and decreased marble burying. In contrast, the same regimen of citalopram treatment had no effect on these behaviors in either non-lactating postpartum or nulliparous females. Our findings demonstrate changes in both central and peripheral 5-HT systems associated with lactation, independent of pregnancy. They also demonstrate a significant interaction of lactation and responsiveness to SSRI treatment, which has important implications in the treatment of PPD. Although recent evidence has cast doubt on the effectiveness of SSRIs, these results support their therapeutic use in the treatment of PPD.

Project description:BackgroundAlthough selective serotonin reuptake inhibitors (SSRIs) are widely prescribed, associations with violence are uncertain.Methods and findingsFrom Swedish national registers we extracted information on 856,493 individuals who were prescribed SSRIs, and subsequent violent crimes during 2006 through 2009. We used stratified Cox regression analyses to compare the rate of violent crime while individuals were prescribed these medications with the rate in the same individuals while not receiving medication. Adjustments were made for other psychotropic medications. Information on all medications was extracted from the Swedish Prescribed Drug Register, with complete national data on all dispensed medications. Information on violent crime convictions was extracted from the Swedish national crime register. Using within-individual models, there was an overall association between SSRIs and violent crime convictions (hazard ratio [HR] = 1.19, 95% CI 1.08-1.32, p < 0.001, absolute risk = 1.0%). With age stratification, there was a significant association between SSRIs and violent crime convictions for individuals aged 15 to 24 y (HR = 1.43, 95% CI 1.19-1.73, p < 0.001, absolute risk = 3.0%). However, there were no significant associations in those aged 25-34 y (HR = 1.20, 95% CI 0.95-1.52, p = 0.125, absolute risk = 1.6%), in those aged 35-44 y (HR = 1.06, 95% CI 0.83-1.35, p = 0.666, absolute risk = 1.2%), or in those aged 45 y or older (HR = 1.07, 95% CI 0.84-1.35, p = 0.594, absolute risk = 0.3%). Associations in those aged 15 to 24 y were also found for violent crime arrests with preliminary investigations (HR = 1.28, 95% CI 1.16-1.41, p < 0.001), non-violent crime convictions (HR = 1.22, 95% CI 1.10-1.34, p < 0.001), non-violent crime arrests (HR = 1.13, 95% CI 1.07-1.20, p < 0.001), non-fatal injuries from accidents (HR = 1.29, 95% CI 1.22-1.36, p < 0.001), and emergency inpatient or outpatient treatment for alcohol intoxication or misuse (HR = 1.98, 95% CI 1.76-2.21, p < 0.001). With age and sex stratification, there was a significant association between SSRIs and violent crime convictions for males aged 15 to 24 y (HR = 1.40, 95% CI 1.13-1.73, p = 0.002) and females aged 15 to 24 y (HR = 1.75, 95% CI 1.08-2.84, p = 0.023). However, there were no significant associations in those aged 25 y or older. One important limitation is that we were unable to fully account for time-varying factors.ConclusionsThe association between SSRIs and violent crime convictions and violent crime arrests varied by age group. The increased risk we found in young people needs validation in other studies.

Project description:Background and Purpose- Selective serotonin reuptake inhibitors (SSRIs) have a well-established association with bleeding complications and conflicting reports on outcome after stroke. We sought to evaluate whether pre-intracerebral hemorrhage (ICH) SSRI use increased ICH risk and post-ICH SSRI use improved ICH outcome. Methods- Through post hoc analysis of the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage), SSRI use was categorized into no use, pre-ICH only, pre- and post-ICH use (termed "continuous"), and post-ICH only (termed "new"). Using multivariable modeling, associations were sought between pre-ICH SSRI use and ICH risk in the case-control set, and associations between post-ICH SSRI use and 3-month outcome were analyzed in the ICH case set. Exploratory analyses sought to assess influence of race/ethnicity in models. Results- The final study cohort consisted of 2287 ICH cases and 2895 controls. Pre-ICH SSRI use was not associated with ICH risk (odds ratio, 0.824 [95% CI, 0.632-1.074]) nor potentiation of ICH risk with anticoagulant or antiplatelet use. New post-ICH SSRI use was associated with unfavorable modified Rankin Scale score at 3 months after ICH (odds ratio, 1.673 [95% CI, 1.162-2.408]; P=0.006) in multivariable analyses. Additional propensity score analysis indicated a similar trend but did not reach statistical significance (P=0.107). When stratified by race/ethnicity, multivariable modeling demonstrated reduced ICH risk with pre-ICH SSRI use in Hispanics (odds ratio, 0.513 [95% CI, 0.301-0.875]; P=0.014), but not non-Hispanic whites or blacks, and no associations between post-ICH SSRI use and 3-month outcome in any racial/ethnic group. Conclusions- In a large multiethnic cohort, pre-ICH SSRI use was not associated with increased ICH risk, but post-ICH SSRI use was associated with unfavorable 3-month neurological outcome after ICH. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT01202864.

Project description:BackgroundSelective serotonin reuptake inhibitors are increasingly used in the long-term treatment of depression. Much of the supporting evidence about the effects of these drugs comes from discontinuation trials, a variant of randomized controlled trials whose design is problematic to interpret. We conducted a systematic review to examine the efficacy and acceptability of long-term therapy with selective serotonin reuptake inhibitors relative to placebo in the treatment of unipolar depression.MethodsWe identified placebo-controlled randomized trials with a treatment duration of at least 6 months by searching MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials to update a recently published systematic review. Efficacy was defined in terms of response to treatment (50% improvement in depression score relative to baseline) and remission (score of 7 or below on the Hamilton rating scale for depression). Key secondary outcomes included quality of life, return to work, need for additional treatment and self-harm. Overall acceptability was defined in terms of dropouts for any reason over a course of treatment.ResultsOf the 2693 records identified initially, we included 6 randomized controlled trials that met our eligibility criteria. These studies had a moderate risk of bias, had assigned a total of 1299 participants with depression to either treatment or placebo and had followed both groups for 6-8 months. We observed statistically significant improvements in response to treatment (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.12-2.48), but not in remission (OR 1.46, 95% CI 0.92-2.32) or acceptability (OR 0.87, 95% CI 0.67-1.14). The effects appeared greater among patients without comorbidities.InterpretationThere is a lack of classic randomized controlled trials of serotonin reuptake inhibitors lasting more than 1 year for the treatment of depression. The results of our systematic review support current recommendations for 6-8 months of antidepressant treatment following initial recovery but provide no guidance for longer treatment.

Dataset Information

Effects of Selective Serotonin Reuptake Inhibitors on Depression-Like Behavior in a Laser-Induced Shock Wave Model.

Publications

Effects of Selective Serotonin Reuptake Inhibitors on Depression-Like Behavior in a Laser-Induced Shock Wave Model.

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