The contribution of relaxation and expectancy to fear reduction via graded, imaginal exposure to feared stimuli.
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Anxiety↗
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Results for “fear”
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Components of desensitization in modification of fear among genuinely fearful subjects.
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Behavior Therapy↗
Comparative Evaluation of Virtual Reality versus Standard Nursing Care in Managing Pain and Fear during Lumbar Puncture Procedures: A Randomised Controlled Trial.
BACKGROUND: Meningitis is a serious infectious disease that can cause significant morbidity and long-term neurological problems. Although a lumbar puncture is a necessary diagnostic procedure, it is often accompanied by discomfort, anxiety, and fear, which can severely impact the patient's experience. Although there is few data on its application prior to lumbar puncture in adult patients with meningitis, immersive virtual reality (VR) has become a promising non-pharmacological technique for lowering procedural distress. Thus, among individuals undergoing lumbar punctures, this randomized controlled research assessed how well pre-procedural VR reduced pain, anxiety, and fear while enhancing patient satisfaction. OBJECTIVE: This study aims to evaluate the effectiveness of virtual reality (VR) in reducing pain and fear among adults undergoing lumbar puncture (LP) compared with standard care protocol. METHODS: A randomised clinical trial was conducted from May to October 2025, using a single-blind, true experimental design. A total of 85 patients were randomly assigned to either the VR intervention group ( n = 41) or the control group receiving standard care ( n = 44). Pain levels were assessed using a visual analogue scale. Fear was assessed using the Multidimensional Fear-of-Injection Scale. Data were analysed using SPSS version 26. RESULTS: According to the study, the findings revealed a significant reduction in pain levels among the study group following the VR intervention, with mean pain scores dropping from 7.54 ± 1.925 to 2.49 ± 0.675. In contrast, the control group showed increased pain intensity, with mean scores rising from 6.84 ± 1.842 to 8.36 ± 1.348. The VR group showed a significant reduction in fear scores across all domains, whereas no significant changes were observed in the control group. Direct fear decreased from 20.12 ± 1.71 to 9.44 ± 2.00, indirect fear from 17.24 ± 1.46 to 8.66 ± 2.24, physiological response improved from 0.34 ± 0.66 to 3.00 ± 1.00 and avoidance behaviour decreased from 16.71 ± 1.49 to 7.80 ± 1.85. CONCLUSIONS: The research shows that the use of VR prior to LP significantly reduces level of pain and fear compared to standard care. These results support VR as a non-pharmacological intervention for fear and pain to improve patient experience during invasive procedures. In contrast, the control group experienced no improvement.Trial Registration: The IRCT code for the trial was IRCT ID 20250803066743N1.
Humans↗
DYRK1A modulates fear memory formation via epigenetic modification.
Fear memory formation is crucial for survival, with the hippocampus playing a central role. This study investigates the behavioral and molecular aspects of fear memory formation, focusing on Dual-specificity tyrosine phosphorylation-regulated kinase 1 A (DYRK1A), a protein known to be critical for cognitive functions. Our results demonstrate that DYRK1A expression in hippocampal CA1 pyramidal neurons is downregulated after contextual fear conditioning (CFC). We also observed a decrease in DYRK1A binding to the Maoa promoter, suggesting its involvement in transcriptional regulation during fear memory formation. In subsequent experiments, we modulated DYRK1A expression using viral vectors. DYRK1A overexpression reduced freezing behavior, while knockdown enhanced it. At the molecular level, DYRK1A overexpression resulted in elevated H3K4me3 levels, while knockdown decreased it. These findings indicate that DYRK1A regulates fear memory formation via epigenetic modifications, altering H3K4me3 levels and influencing Maoa transcription in the hippocampus. This research highlights the nuclear role of DYRK1A and suggests its potential as a therapeutic target for neuropsychiatric disorders related to fear and memory.
Animals↗
PUS7-dependent Ψ reshapes specific synaptic gene exons to facilitate fear extinction memory formation.
RNA modifications serve as dynamic regulators of neural plasticity through their ability to fine-tune transcript stability and splicing. Pseudouridine (Ψ), an evolutionarily conserved RNA modification catalyzed by pseudouridine synthases, plays established roles in neurodevelopment, yet its functional significance in activity-dependent behavioral adaptation remains poorly defined. Here, we investigate Ψ-mediated epitranscriptomic regulation within the infralimbic prefrontal cortex (ILPFC), a brain region requiring precise synaptic remodeling for the clinically relevant form of fear extinction memory. Combining transcriptome-wide pseudouridylation profiling with behavioral analysis in mice, we identified selective Ψ enrichment at exons of synaptic regulatory genes within ILPFC during fear extinction learning. Fear extinction in the ILPFC drives concomitant exonic Ψ deposition and upregulation of synaptogenic transcripts, processes that involve pseudouridine synthase PUS7. Crucially, PUS7 knockdown in the ILPFC selectively impaired fear extinction memory formation without altering baseline fear expression, establishing a causal link between Ψ-dependent RNA processing and activity-dependent synaptic structural remodeling in this microcircuit. Our findings demonstrate that PUS7-mediated Ψ modification spatiotemporally regulates activity-dependent RNA dynamics in the ILPFC, providing the evidence that epitranscriptomic mechanisms precisely coordinate synaptic gene expression within behaviorally defined brain sub-region. This work bridges molecular RNA biology with systems neuroscience, revealing a novel mechanism for activity-dependent regulation of fear extinction in ILPFC.
Animals↗
The effect of morphine on fear extinction in rats.
Rats were trained on an appetitive discretetrial discriminated-punishment task in which they learned to suppress responding when an intense flashing light predicting punishment was present and to respond rapidly on trials when the flashing light was absent. Once animals were performing discriminatively, 0.75, 3.0, or 6.0 mg/kg of morphine (base) was administered and a fear extinction session consisting of 60 nonshocked presentations of the flashing light was given. Two saline control groups, one that received fear extinction and one that did not, were also included in the experiment. On the day following fear extinction, all rats were tested in the undrugged state on the discriminated punishment problem, but without shock. The rats receiving 3.0 and 6.0 mg/kg of morphine before the fear extinction session were suppressed by the flashing light more than the saline extinction group or the 0.75 mg/kg morphine treatment group. Moreover, the two higher dose morphine groups were suppressed as readily as the saline group that received no fear extinction. These results are attributed to the antiemotionality effects of morphine.
Animals↗
Beyond Glycaemia: Fear of Hypoglycaemia, Cognition and Functional Mobility After Advanced Hybrid Closed-Loop Therapy in Older Adults With Type 1 Diabetes: A Prespecified Secondary Analysis of a Randomised, Single-Centre Study.
BACKGROUND: Evidence on psychological, cognitive and functional outcomes of advanced diabetes technologies in older adults with long-standing type 1 diabetes (T1D) remains limited. We evaluated whether initiation of advanced hybrid closed-loop (AHCL) therapy was associated with changes in fear of hypoglycaemia, diabetes distress, psychological well-being, cognition, frailty-related measures and mobility-related function in adults aged ≥ 65 years with T1D. METHODS: This prespecified, exploratory secondary analysis was conducted within a single-centre, open-label, randomised, controlled, parallel-group trial including adults aged ≥ 65 years with long-standing T1D. Participants were randomly assigned (1:1) to initiate AHCL therapy using the MiniMed 780G system or to continue standard diabetes treatment. The secondary outcomes included WHO-5, the 17-item Diabetes Distress Scale (DDS), Hypoglycemia Fear Survey-II (HFS-II), Montreal Cognitive Assessment, Digit Symbol Substitution Test, Fried frailty phenotype and performance-based functional measures. No formal sample-size calculation was performed for these secondary outcomes. RESULTS: Thirty-one participants were randomised and 29 completed 12 months of follow-up and were included in the treatment-effect analyses. In the baseline-adjusted primary analysis, AHCL therapy was associated with a lower HFS-II score than standard treatment (adjusted mean difference -18.9; 95% CI: -32.4 to -5.4; nominal p = 0.008), although this finding did not remain statistically significant after Holm correction (adjusted p = 0.104) or in an exploratory model additionally adjusted for sex (difference -13.6; 95% CI: -32.2 to 5.0; p = 0.145). Diabetes distress, psychological well-being, global cognition and processing speed did not differ between groups. In sex-adjusted sensitivity analyses, the between-group differences remained statistically significant for 6-min walk distance (92.6 m; 95% CI: 36.8 to 148.3; p = 0.002) and Timed Up and Go performance (-2.27 s; 95% CI: -4.28 to -0.27; p = 0.028), but not for gait speed (0.27 m/s; 95% CI: -0.05 to 0.59; p = 0.099). At 12 months, 12 of 14 AHCL participants were robust and 2 were pre-frail; in the control group, 11 of 15 were robust and 4 were pre-frail. No participant was classified as frail at follow-up. CONCLUSIONS: In this small, selected cohort, AHCL therapy was associated with a nominally lower fear-of-hypoglycaemia score and better performance on selected mobility-related tests over 12 months. The fear-of-hypoglycaemia finding did not remain statistically significant after correction for multiple comparisons or additional adjustment for sex. Six-minute walk distance and Timed Up and Go remained statistically significant in the exploratory sex-adjusted sensitivity analyses, whereas the gait-speed difference did not. No measurable between-group deterioration in global cognition or processing speed was observed. These exploratory findings require confirmation in larger studies with balanced representation by sex and direct measurement of physical activity. These findings also support a person-centred clinical message: older age alone should not be regarded as a barrier to AHCL when treatment is introduced with individualised education and appropriate ongoing support.
Humans↗
Treatment of fear-induced aggression in a horse.
Desensitization (gradually exposing an animal to a fear-inducing stimulus without evoking the fear response) and counter-conditioning (rewarding the animal for behavior incompatible with the fear response) are highly successful ways of eliminating or reducing fear responses and corresponding aggression.
Aggression↗
Prevalence and pattern of psychological symptoms in form of dental fear and anxiety in children and adolescents with traumatic dental injuries: a systematic review.
BACKGROUND/AIMS: This systematic review aimed to evaluate the level and pattern of dental fear and anxiety (DFA) amongst children and adolescents with traumatic dental injuries (TDI) and, where available, to compare these outcomes with non-traumatised controls. METHODS: An a priori protocol was developed and registered in PROSPERO (CRD420261329946). A comprehensive literature search was conducted in PubMed, EMBASE, Web of Science, and Scopus on 3 March 2026, with additional grey literature, citation, and reference searching. No language or time restrictions were applied. Observational clinical studies assessing DFA in individuals with TDI using validated tools were included. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Joanna Briggs Institute checklist. Certainty of evidence was evaluated using the GRADE approach. RESULTS: A total of 2885 records were identified, of which 4 cross-sectional studies met the inclusion criteria after screening. Studies were conducted in Croatia and Kosovo and included paediatric populations. Sample sizes ranged from 147 to 505 participants. Different validated scales (CFSS-DS, CDAS, S-DAI) were used to assess DFA. Overall, children with TDI demonstrated predominantly low levels of dental fear and anxiety across assessment tools. However, findings were inconsistent, with some studies reporting lower or similar anxiety levels in TDI patients compared to controls. Risk of bias was moderate or high in three of the four studies, and the overall certainty of evidence was rated as low to very low due to methodological limitations, heterogeneity, and imprecision. CONCLUSION: The limited available evidence suggests that children and adolescents with TDI do not consistently present with higher levels of dental fear and anxiety than non-traumatised controls. These findings indicate that TDI does not inherently cause DFA, underscoring the critical role of empathetic behaviour support in mitigating post-traumatic dental fear. However, the evidence is based on a small number of regionally concentrated cross-sectional studies with low to very low certainty. Future prospective studies using standardised TDI classifications, validated DFA instruments, and clearly defined assessment time points are needed.
Dental anxiety↗
Complementation testing identifies genes mediating effects at quantitative trait loci underlying fear-related behavior.
Knowing the genes involved in quantitative traits provides an entry point to understanding the biological bases of behavior, but there are very few examples where the pathway from genetic locus to behavioral change is known. To explore the role of specific genes in fear behavior, we mapped three fear-related traits, tested fourteen genes at six quantitative trait loci (QTLs) by quantitative complementation, and identified six genes. Four genes, Lamp, Ptprd, Nptx2, and Sh3gl, have known roles in synapse function; the fifth, Psip1, was not previously implicated in behavior; and the sixth is a long non-coding RNA, 4933413L06Rik, of unknown function. Variation in transcriptome and epigenetic modalities occurred preferentially in excitatory neurons, suggesting that genetic variation is more permissible in excitatory than inhibitory neuronal circuits. Our results relieve a bottleneck in using genetic mapping of QTLs to uncover biology underlying behavior and prompt a reconsideration of expected relationships between genetic and functional variation.
Animals↗
Noradrenergic agonists and antagonists: effects on conditioned fear as measured by the potentiated startle paradigm.
Clonidine (10-40 microgram/kg) produced a dose-dependent reduction of fear as measured by the potentiated startle effect (increased acoustic startle in the presence of a cue which had been previously paired with shock). The reduction of potential startle could not be accounted for entirely by a general depressant effect of clonidine on startle nor by an acceleration of extinction. Piperoxane and yohimbine, which are associated with anxiety in humans, increased potentiated startle, whereas propranolol and WB-4101 did not. These results provide further evidence that the potentiated startle paradigm in the rat is sensitive to drug that alter anxiety in humans. Moreover, they support the hypothesis that norepinephrine transmission is important for the expression of fear or anxiety.
Animals↗
Male and Female Mice Show Similar Fear Memory Performance Despite Hippocampal Immediate Early Gene Expression Differences During Encoding and Consolidation.
Accurate and efficient memory processing is essential for survival. A body of ongoing work in both human subjects and animal models suggests that memory processing may differ substantially between males and females. In mice, contextual fear memory (CFM) encoding, consolidation, and recall have been well studied, and the mouse hippocampus and amygdala have been implicated in these processes. The present pilot study addresses whether the activation of these brain regions differs substantially between male and female mice at each stage of CFM processing. We find that male and female mice show no differences in sleep behavior, which is essential for CFM consolidation, following single-trial contextual fear conditioning (CFC). We also find no significant differences in CFM recall performance between male and female mice. However, females show a trend for larger increases in CA1 cFos expression, relative to males, during CFM encoding. On the other hand, only males-but not females-show an apparent increase in cFos expression among dentate gyrus (DG) granule cells during CFM consolidation. Males also show a trend for a larger apparent reduction in cFos in CA1 and CA3 during CFM consolidation, relative to females. These preliminary findings highlight the idea that the neurobiological underpinnings of memory processing may differ between males and females, even when performance during recall is identical.
Animals↗
Using a hospital for desensitization of an outpatient's illness-related fears.
An outpatient with phobias related to enclosed places, hospitals, doctors, and cancer was treated by systematic desensitization; the facilities of a general hospital were used for part of the process. Steps in treatment included securing a complete psychiatric and social history, teaching the patient relaxation therapy techniques, and establishing a hierarchy of anxiety-provoking stimuli specifically related to the patient's fears. After desensitization the patient was able to enter the hospital for tests for a physical ailment and showed a general decrease in her fears.
Adult↗
How prevalent is fear of cancer recurrence beyond 5 years: a systematic review of validated assessments across tumour types.
PURPOSE: Fear of cancer recurrence (FCR) is an established challenge for cancer survivors. Research however has largely focussed early in treatment, with varying assessments and often single tumour sites. This systematic review set out to determine prevalence of FCR in survivors beyond 5 years across all tumour types. METHOD: We designed a search strategy to identify publications assessing FCR in survivors beyond 5 years with sample size greater than 50, using validated measures. Applying PRISMA methodology and with defined inclusion and exclusion criteria two authors independently assessed the studies for eligibility. Data extraction recorded number of participants, tumour type, study design, FCR tool, time points for assessment and reported prevalence. Risk of bias was assessed to address quality. RESULTS: Ten papers were included, reporting FCR from 5 years to beyond 20 years. Validated tools employed were FCRI-SF and FOP-Q-SF. Sample sizes ranged from 64 to 5983 participants, with a heterogeneous mix of tumour types and age. Only two studies reported longitudinal measurements. Prevalence of FCR above defined threshold ranged from 13 to 33.9% for those studies with acceptable risk of bias reporting distinct cohorts beyond 5 years. CONCLUSION: The limited evidence suggests that clinically relevant FCR persists in some survivors at 5 years. Our review demonstrates the challenge of heterogeneous patient populations in FCR research emphasising the need for improved consensus on measurements and more prospective longitudinal research representing a comprehensive variety of tumour types. We address the clinical implications of persistent FCR and the need to implement effective interventions.
Humans↗
Diazepam and flurazepam: effects on conditioned fear as measured with the potentiated startle paradigm.
Diazepam (0.3, 0.6, 1.2, or 2.5 mg/kg) produced a dose-dependent reduction of the potentiated startle effect where acoustic startle amplitude is normally increased in the presence of a light previously paired with a shock. Even the lowest dose tested (0.3 mg/kg) significantly attenuated potentiated startle. The effect was selective since the same doses did not depress baseline startle amplitude measured in the same animals in the same test session. A 2 X 2 design in which rats were trained and tested under the same or different drug condition (diazepam or saline) showed the results could not be explained by state-dependent learning. The primary effect of diazepam was to block expression of rather than acquisition of fear as measured by potentiated startle. Flurazepam (2.5, 10, or 20 mg/kg) also reduced potentiated startle selectively but was 6--8 times less potent than diazepam. These and other results suggest that the potentiated startle paradigm, as a measure of classical conditioning that involves no operant, might provide a useful adjunct to behavioral methods currently being used to analyze antianxiety compounds.
Animals↗
Factors affecting the measurement of classically conditioned fear in rats following exposure to escapable versus inescapable signaled shock.
Three experiments are reported in which rats first received 50 escapable or inescapable signaled-shock trials. Experiment 1 (n = 22) employed an acquired-drive paradigm and found inescapable shock subjects learned a hurdle-jump response to escape the signal less rapidly than did escapable-shock subjects. Experiment 2 (n = 24) employed a conditioned emotional response paradigm and found inescapable-shock subjects suppressed more when the signal was introduced in the appetitive bar-pressing task. Both experiments measured spontaneous activity immediately following conditioning and found no group differences. Experiment 3 (n = 39) employed the same activity task and found no difference between escapable- and inescapable-shock groups when the signal was introduced into the activity task. Both groups displayed less activity than a nonshock control group during the signal. The results suggest that lack of control over the shock in the conditioning phase did not result in an increase of conditioned fear. The results are discussed in terms of a learned active-inactive predisposition to respond.
Animals↗
The effect of lorazepam on the vasoconstriction of fear.
Volume-pulse digital plethysmography performed under ideal conditions on relatively fit adults has shown that lorazepam 4 mg intravenously abolishes the vasoconstriction of fear and restores the digital vasodilatation of the tranquil mind. The sedative effect of the drug is prolonged and is associated with several hours of anterograde amnesia from the time of its administration. The drug has no effect on the vasoconstrictor reaction to cold, pain, noise or other forms of adrenergic stimuli. Lorazepam seems to modify or prevent the psychomotor reactions which may complicate ketamine anaesthesia.
Adult↗
Reduction of fear-related dental management problems with use of filmed modeling.
In this study of the modification of anxiety-related disruptive behavior in dental treatment, matched groups of inner-city children attending a pedodontic clinic were shown a videotaped demonstration of a 4-year-old black child undergoing a dental restorative procedure or were given an unrelated drawing task before dental treatment. Children who viewed the videotape demonstration of a peer model coping with dental procedures showed significantly fewer fear-related disruptive behaviors during restoration of lesions. Observations of children's anxiety levels made by dentists and independent observers validated the effectiveness of viewing the videotaped demonstration. No significant correlation was found between the children's reports of their anxiety and their behavior during dental treatment.
Analysis of Variance↗