The effect of SSRIs on fear learning:A systematic review and meta-analysis

RationaleSelective serotonin reuptake inhibitors (SSRIs) are considered first-line medication for anxiety-like disorders such as panic disorder, generalized anxiety disorder, and post-traumatic stress disorder. Fear learning plays an important role in the development and treatment of these disorders. Yet, the effect of SSRIs on fear learning are not well known.ObjectiveWe aimed to systematically review the effect of six clinically effective SSRIs on acquisition, expression, and extinction of cued and contextual conditioned fear.MethodsWe searched the Medline and Embase databases, which yielded 128 articles that met the inclusion criteria and reported on 9 human and 275 animal experiments.ResultsMeta-analysis showed that SSRIs significantly reduced contextual fear expression and facilitated extinction learning to cue. Bayesian-regularized meta-regression further suggested that chronic treatment exerts a stronger anxiolytic effect on cued fear expression than acute treatment. Type of SSRI, species, disease-induction model, and type of anxiety test used did not seem to moderate the effect of SSRIs. The number of studies was relatively small, the level of heterogeneity was high, and publication bias has likely occurred which may have resulted in an overestimation of the overall effect sizes.ConclusionsThis review suggests that the efficacy of SSRIs may be related to their effects on contextual fear expression and extinction to cue, rather than fear acquisition. However, these effects of SSRIs may be due to a more general inhibition of fear-related emotions. Therefore, additional meta-analyses on the effects of SSRIs on unconditioned fear responses may provide further insight into the actions of SSRIs

COVID-19 lockdown effects on academic functioning, mood, and health correlates:data from Dutch pharmacy students, PhD candidates and postdocs

Mixed results have been published on the impact of the 2019 coronavirus (COVID-19) pandemic and its associated lockdown periods on academic functioning, mood, and health correlates such as alcohol consumption. Whereas a number of students report an impaired academic performance and increased alcohol intake during lockdown periods, other students report no change or an improvement in academic functioning and a reduced alcohol consumption. This data descriptor article describes the dataset of a study investigating the impact of the COVID-19 pandemic on academic functioning. To investigate this, an online survey was conducted among Dutch pharmacy students, PhD candidates and postdoctoral researchers (postdocs) of Utrecht University, the Netherlands. Compared to before the COVID-19 pandemic, the survey assessed possible changes in self-reported academic functioning, mood and health correlates such as alcohol consumption, perceived immune functioning and sleep quality. Retrospective assessments were made for four periods, including (1) the year 2019 (the period before COVID-19), (2) the first lockdown period (15 March–11 May 2020), (3) summer 2020 (no lockdown) and (4) the second lockdown (November 2020–April 2021). This article describes the content of the survey and corresponding dataset. The survey had a response rate of 24.3% and was completed by 345 participants

Transition to online education during the COVID-19 pandemic:impact of changes in alcohol consumption and experiencing hangovers on academic functioning

In the Netherlands, the 2019 coronavirus (COVID-19) pandemic had a significant impact on daily life, with two extensive lockdowns enforced to combat the spread of the SARS-CoV-2 virus. These measures included the closure of bars and restaurants, and the transition from face-to-face to online education. A survey was conducted among Dutch pharmacy students and PhD-candidates to investigate the impact of COVID-19 lockdown on alcohol consumption, hangovers, and academic functioning. The analysis revealed a significant reduction in both quantity and frequency of alcohol consumption during the COVID-19 lockdown periods. This was accompanied with a significant reduction in hangover frequency and lower hangover severity during COVID-19 lockdown periods. The distribution of scores on academic performance showed great variability between respondents: while some participants reported impairment, others reported improved performance during the COVID-19 pandemic, or no change. Women reported that significantly more time investment was associated with maintaining these performance levels. Consistent among participants was the notion of reduced interactions with teachers and other students. Participants who reported more hangovers and most severe hangovers before COVID-19 benefited from the lockdown periods in terms of improved academic performance. Positive correlations were found between study grades/output and both the frequency and severity of hangovers experienced before COVID-19, suggesting that heavier drinkers, in particular, improved academic performance during the lockdown periods. In conclusion, COVID-19 lockdowns were associated with a significant reduction in both alcohol consumption and experiencing hangovers, which was, among heavier drinkers particularly, associated with significantly improved academic functioning

The effect of SSRIs on fear learning: a systematic review and meta-analysis

RATIONALE: Selective serotonin reuptake inhibitors (SSRIs) are considered first-line medication for anxiety-like disorders such as panic disorder, generalized anxiety disorder, and post-traumatic stress disorder. Fear learning plays an important role in the development and treatment of these disorders. Yet, the effect of SSRIs on fear learning are not well known. OBJECTIVE: We aimed to systematically review the effect of six clinically effective SSRIs on acquisition, expression, and extinction of cued and contextual conditioned fear. METHODS: We searched the Medline and Embase databases, which yielded 128 articles that met the inclusion criteria and reported on 9 human and 275 animal experiments. RESULTS: Meta-analysis showed that SSRIs significantly reduced contextual fear expression and facilitated extinction learning to cue. Bayesian-regularized meta-regression further suggested that chronic treatment exerts a stronger anxiolytic effect on cued fear expression than acute treatment. Type of SSRI, species, disease-induction model, and type of anxiety test used did not seem to moderate the effect of SSRIs. The number of studies was relatively small, the level of heterogeneity was high, and publication bias has likely occurred which may have resulted in an overestimation of the overall effect sizes. CONCLUSIONS: This review suggests that the efficacy of SSRIs may be related to their effects on contextual fear expression and extinction to cue, rather than fear acquisition. However, these effects of SSRIs may be due to a more general inhibition of fear-related emotions. Therefore, additional meta-analyses on the effects of SSRIs on unconditioned fear responses may provide further insight into the actions of SSRIs

Pharmacological modulation of conditioned fear in the fear-potentiated startle test: a systematic review and meta-analysis of animal studies

RATIONALE AND OBJECTIVES: Fear conditioning is an important aspect in the pathophysiology of anxiety disorders. The fear-potentiated startle test is based on classical fear conditioning and over the years, a broad range of drugs have been tested in this test. Synthesis of the available data may further our understanding of the neurotransmitter systems that are involved in the expression of conditioned fear. METHODS: Following a comprehensive search in Medline and Embase, we included 68 research articles that reported on 103 drugs, covering 56 different drug classes. The systematic review was limited to studies using acute, systemic drug administration in naive animals. RESULTS: Qualitative data synthesis showed that most clinically active anxiolytics, but not serotonin-reuptake inhibitors, reduced cued fear. Anxiogenic drugs increased fear potentiation in 35% of the experiments, reduced fear potentiation in 29% of the experiments, and were without effect in 29% of the experiments. Meta-analyses could be performed for five drug classes and showed that benzodiazepines, buspirone, 5-HT 1A agonists, 5-HT 1A antagonists, and mGluR2,3 agonists reduced cued conditioned fear. The non-cued baseline startle response, which may reflect contextual anxiety, was only significantly reduced by benzodiazepines and 5-HT 1A antagonists. No associations were found between drug effects and methodological characteristics, except for strain. CONCLUSIONS: The fear-potentiated startle test appears to have moderate to high predictive validity and may serve as a valuable tool for the development of novel anxiolytics. Given the limited available data, the generally low study quality and high heterogeneity additional studies are warranted to corroborate the findings of this review

Covid-19 lockdown effects on academic functioning, mood, and health correlates: Data from dutch pharmacy students, phd candidates and postdocs

Mixed results have been published on the impact of the 2019 coronavirus (COVID-19) pandemic and its associated lockdown periods on academic functioning, mood, and health correlates such as alcohol consumption. Whereas a number of students report an impaired academic performance and increased alcohol intake during lockdown periods, other students report no change or an improvement in academic functioning and a reduced alcohol consumption. This data descriptor article describes the dataset of a study investigating the impact of the COVID-19 pandemic on academic functioning. To investigate this, an online survey was conducted among Dutch pharmacy students, PhD candidates and postdoctoral researchers (postdocs) of Utrecht University, the Netherlands. Compared to before the COVID-19 pandemic, the survey assessed possible changes in self-reported academic functioning, mood and health correlates such as alcohol consumption, perceived immune functioning and sleep quality. Retrospective assessments were made for four periods, including (1) the year 2019 (the period before COVID-19), (2) the first lockdown period (15 March–11 May 2020), (3) summer 2020 (no lockdown) and (4) the second lockdown (November 2020–April 2021). This article describes the content of the survey and corresponding dataset. The survey had a response rate of 24.3% and was completed by 345 participants

No effect of sex and estrous cycle on the fear potentiated startle response in rats

The prevalence of anxiety disorders is higher in women than in men. Yet preclinical studies on anxiety are mostly performed in male subjects. This may have limited our understanding of mechanisms contributing to anxiety disorders. Since fear conditioning is considered an important factor in the etiology of anxiety disorders, the present study aimed to investigate the effect of sex and estrous cycle on conditioned fear and the anxiolytic effect of benzodiazepines in rats. We measured the fear-potentiated startle response in male and female rats during different estrous cycle stages and performed a replication study in a separate cohort. In addition, we assessed the response to diazepam (0–3.0 mg/kg IP) and chlordiazepoxide (0–10 mg/kg IP) in male and female rats in proestrous/estrous and diestrous stage. Our results showed that there were no sex differences in the expression of fear-potentiated startle. The estrous cycle also did not affect the fear-potentiated startle response. In addition, male and female rats did not differ in their fear-potentiated startle response following treatment with either diazepam or chlordiazepoxide. In conclusion, the current study shows that male and female rats do not differ in their conditioned fear response and the responsiveness to benzodiazepines. The results further indicate that conditioned fear-related processes are not affected by gonadal hormone fluctuations in this paradigm. These findings may suggest that the higher prevalence of anxiety disorders in women more likely results from differences in responding to previous experiences or differences in other predisposing factors, rather than differences in conditioned fear per se

Lifelong, central corticotropin-releasing factor (CRF) overexpression is associated with individual differences in cocaine-induced conditioned place preference

Stress, through corticotropin-releasing factor (CRF), influences all aspects of cocaine addiction. Earlier studies suggest that individual differences in responsivity to stress affect susceptibility to develop addiction. We have previously found that CRF over-expression alters individual differences in behavioural responses to novelty stress in mice. Therefore, we hypothesised that post-natal, long-term over-expression of brain CRF may alter the rewarding effects of cocaine in a manner that is sensitive to individual differences. In this study we specifically investigated cocaine-induced conditioned place preference (CPP) in transgenic mice over-expressing CRF (CRF-OE) and in wild-type (WT) littermates after determining their individual locomotor and emotional responsivity to inescapable novelty. CRF-OE mice showed decreased overall locomotor activity and increased anxiety-like behaviour in response to novelty compared to WT mice. Low behavioural reactivity to novelty (LR) was associated with heightened anxiety-like behaviour in CRF-OE, but not in WT, mice. WT and CRF-OE mice developed CPP equally to both low (5 mg/kg) and high (20 mg/kg) doses of cocaine. However, LR CRF-OE mice expressed significantly stronger cocaine CPP than transgenic mice with high locomotor response to novelty (HR). In WT mice, on the other hand, stronger CPP induced by 20 mg/kg of cocaine was found in the HR animals. Furthermore, there was a strong negative correlation between locomotor reactivity to novelty and CPP in CRF-OE, but not in WT, mice. Collectively, these results suggest that long-term, post-natal CRF over-expression increases the rewarding effects of cocaine in individuals with high emotional response to stress