Prefrontal tetanic stimulation, following fear reconditioning, facilitates expression of previously acquired extinction.

We have recently shown that post-extinction retraining of rats, with a shock intensity that is too weak to induce by itself significant fear acquisition, impairs the recall of fear extinction memory. Tetanic stimulation (TS) of the medial prefrontal cortex (mPFC), applied before or following this retraining, facilitates extinction recall. Here we investigated whether mPFC TS can also facilitate expression of fear extinction when rats are retrained with the same shock intensity as during the initial fear acquisition. Rats were implanted with stimulating electrodes in the mPFC and were trained to acquire freezing to a conditioning chamber, in which they had to enter freely. In Experiment 1, extinction of this response was followed by reconditioning and then another extinction training. Acquired freezing was extinguished successfully, while reacquired freezing, which was associated with increased chamber entry latencies, was resistant to subsequent extinction. Both reacquired freezing and increased chamber entry latencies were absent in rats that received post-reconditioning mPFC TS. In Experiment 2, post-conditioning mPFC TS had no effect on initially acquired freezing. In Experiment 3, rats were submitted to reconditioning without experiencing extinction training. In this condition, both reacquired freezing and increased chamber entry latencies were still present in rats that received post-reconditioning mPFC TS. These findings provide additional evidence for the fundamental role of the mPFC in maintaining expression of fear extinction.

Prefrontal high-frequency stimulation prevents sub-conditioning procedure-provoked, but not acute stress-provoked, reemergence of extinguished fear.

We have recently shown that post-extinction exposure of rats to a sub-conditioning procedure (SCP, i.e., retraining with a shock intensity that is too weak to induce by itself significant fear conditioning) or to acute stress provokes reemergence of extinguished fear. Furthermore, this SCP effect can be abolished by high-frequency stimulation (HFS) of the medial prefrontal cortex (mPFC), when applied following the SCP. The aim of the present study was to test whether HFS of the mPFC is effective in preventing both SCP-induced and acute stress-provoked fear reemergence. Rats implanted with stimulating electrodes in the mPFC were trained to acquire high levels of freezing to conditioned auditory cue. This fear response was then extinguished. Three weeks later, no spontaneous recovery was observed, but rats exposed to either the SCP or acute stress again exhibited high levels of freezing. HFS of the mPFC, applied before provoking fear reemergence, prevented the effects of SCP, but not acute stress. These data suggest that acute stress may have more impact on functions of the mPFC and/or associated structures than a situational reminder of fear conditioning.

Low-frequency stimulation of the ventral hippocampus facilitates extinction of contextual fear.

Difficulties to treat fear-associated disorders, including posttraumatic stress disorder, are thought to result from dysfunction in fear extinction learning and/or memory. Animal studies on extinction modulation are therefore promising for the development of new treatments. Recent rat studies, including ones using low-frequency stimulation (LFS), have demonstrated that the ventral hippocampus (VH) modulates extinction memory. The present study explores whether the VH also modulates extinction learning. For this, rats were implanted with stimulating electrodes in the VH and experienced contextual fear conditioning, followed 6 or 24 h later by VH LFS and three sessions of extinction training. We found that, whatever the delay used (6 or 24 h), animals that received VH LFS displayed persistent low levels of freezing from the second extinction session, whereas control rats showed low levels of freezing only during the third session. In animals submitted to a stress condition (provoked by a single inescapable foot-shock followed by three sessions of situational reminders) prior to fear conditioning, VH LFS also reduced freezing levels, which, in contrast, remained high in control rats during the course of extinction training. These data suggest that LFS, targeting the VH, may be useful in reducing fear responses during extinction learning.

Study protocol: how does parental stress measured by clinical scales and voice acoustic stress markers predict children's response to PTSD trauma-focused therapies?

INTRODUCTION: Post-traumatic stress disorder (PTSD) symptoms in youth are influenced by parental anxiety and stress. When parents have high levels of stress or have developed PTSD themselves, children tend to show more anxiety symptoms. Parental stress can affect the severity of children's PTSD and lower the success of recovery. However, the influence of parental stress on the effectiveness of trauma-focused therapies (eye movement desensitisation and reprocessing and cognitive behavioural therapy) has not yet been investigated to our knowledge. Hence, we will measure parental stress (using both validated scales and vocal acoustic markers) and investigate how it influences children's PTSD recovery. METHOD AND ANALYSIS: Sixty children between the ages of 7 and 15 years who experienced type 1 trauma will be recruited at the Nice Pediatric Psychotrauma Center in France. We plan to measure stress using two different approaches. We will ask parents to answer validated scales of stress and mood in general. Stress will also be measured using vocal acoustic markers. Parents will be recorded while narrating their child's trauma and during the narrative of a positive and neutral recall of events. Child participants will have to complete anxiety, PTSD and depression scales before the beginning of the trauma-focused therapy and after 3 months of treatment.Linear mixed effects models and differential statistics, such as significance testing corrected for multiple testing, will be used to determine the validity of speech features for the proposed hypotheses. Repeated measures analysis of variance will be performed on the clinical scales scores according to parental stress. Correlations will be performed between clinical scales of parents and children according to time of assessment. ETHICS AND DISSEMINATION: This study was approved by the Committee for the Protection of Individuals of the University of Nice Sophia Antipolis (CERNI) on 21 February 2022, under the number CER2022-015.All participants will be informed that this is an observational study and their consent taken prior to the experiment. Participants will be informed that they can withdraw from the study at any time and that it would not affect the care provided. TRIAL REGISTRATION NUMBER: CER AVIS n° 2022-015.

Storm Alex: acute stress responses in the pediatric population.

Introduction: On 2 October 2020, a violent storm (Alex) reached the French Riviera and caused significant damage in three inhabited valleys in the hinterland of the city of Nice. Entire populations were exposed to prolonged stress (no means of communication, electricity nor water) and were particularly at risk of suffering from psychological consequences. We first hypothesized that a majority of children would experience an acute stress reaction. However, we also hypothesized that their clinical expression would differ depending on their developmental age. Thus, we aimed to evaluate, according to the child's level of development, the presence of acute stress symptoms. Methods: Consecutive interviews with the child/adolescent and his/her parents were conducted by child and adolescent psychologists and psychiatrists to assess symptomatology following storm Alex (from day 1 to day 3). Each interview assessed nine classes of symptoms that have been compared according to age-groups. Results: 116 children have been evaluated (0.2-17.6 years, mean 9.1). The 0-5-years-old showed more agitation as well as developmental regression than children aged 6-11 (p = .011, p = .045) and 12-18 years (p < .001, p < .001). Anxiety was reported more frequently among the 6-11 years old than the 0-5 years children (p = .018). Overall, the interviewed children presented at least one manifestation of acute stress after the storm (94% for the 0-5 years; 83% for the 6-11 years and 74% for the 12-18 years). Discussion: The results highlight the high rate of acute stress symptoms in a natural disaster context, their specificity depending on children's age. Therefore; it emphasizes the need to develop, improve and validate specific assessment tools. Scheduled follow-up evaluations will help to understand, after a natural disaster, the long-term stress response in children, paving the way for targeting early, intensive, specific and multidisciplinary symptomatic treatment approaches.Trial registration: ClinicalTrials.gov identifier: NCT04850924. HIGHLIGHTS: Acute stress symptoms in children and adolescents are very frequent in the context of exposure to a natural disaster with specifications depending on the developmental age.

A 3-year retrospective study of 866 children and adolescent outpatients followed in the Nice Pediatric Psychotrauma Center created after the 2016 mass terror attack.

Background: The mass terrorist attack in Nice, France, in July 2016 caused deaths and injuries in a local population, including children and adolescents. The Nice Pediatric Psychotrauma Center (NPPC) was opened to provide mental health care to the pediatric population (0-18 years) who experienced traumatic events. Objectives: This study describes the specificity of the care pathway for young trauma victims, with an explanation of how the NPPC works during the first three years. Methods: In this retrospective study, we conducted quantitative and qualitative data collection about new and follow-up consultations, primary and comorbid diagnoses, and the kind of trauma (terrorist attack versus other kinds of trauma). Ethics approval was obtained from the local Ethics committee. Results: 866 children and adolescents were followed in the NPPC. We found a high rate of Post-Traumatic Stress Disorder (PTSD; 71%) in this population with a high rate of comorbidities (67%), mainly sleep disorders (34.7%) and mood and anxiety disorders (16.2%). A high number of children and adolescents impacted by the terrorist attack required follow-up consultations after exposure to the mass terrorist attack, the first care-seeking requests continued to occur three years later, although at a slower rate than in the first and second years. New consultations for other kinds of trauma were observed over time. Discussion: This study supports previous findings on the significant impact of mass trauma in the pediatric population showing even a higher level of PTSD and a high rate of comorbidities. This may be explained by the brutality of the traumatic event, particularly for this age group. The findings of this study have implications for early interventions and long-term care for children and adolescents to prevent the development of chronic PTSD into adulthood.

Remote training as a common tool for the different professionals involved in the acute phase after terror attacks across Europe: Perspectives from an expert panel.

The acute response after a terror attack may have a crucial impact on the physical and psychological wellbeing of the victims. Preparedness of the professionals involved in the acute response is a key element to ensure effective interventions, and can be improved through trainings. Today in Europe there is a recognized lack of inter-professional and international trainings, which are important, among others, to respond to the needs and the rights of victims affected by a terrorist attack in another country than their home country. In this paper we report the perspectives of an expert panel composed by different categories of professionals on the possible role of interprofessional trainings provided remotely. The experts discussed the pertinence of remote trainings for professionals involved in the acute response of a terror attack, and highlighted their Strengths, Weaknesses, Opportunities and Threats (SWOT analysis). We concluded that, while remote trainings cannot replace in-person trainings, they may be useful to share knowledge about the role and the organization of the different categories of professionals, thus potentially improving response coordination, and to easily share good practices across professionals and countries.

CoCo20 protocol: a pilot longitudinal follow-up study about the psychiatric outcomes in a paediatric population and their families during and after the stay-at-home related to coronavirus pandemic (COVID-19).

INTRODUCTION: In the context of a viral outbreak and the stay-at-home measures, a significant increase in psychological distress, such as stress or fear behaviours, has previously been reported in adult and paediatric population. Children and adolescents seem to be particularly at risk of developing psychiatric disorders during and after the stay-at-home but evidences are lacking. The main objective of this article is to present the methodology of Coronavirus Confinement 2020 (CoCo20) Study, which aims to assess the impact of the coronavirus pandemic (COVID-19) and stay-at-home on the development of psychiatric disorders, including post-traumatic stress disorder (PTSD), in children and adolescents. METHODS AND ANALYSIS: We describe a longitudinal and multicentre study in the paediatric population during and after stay-at-home related to COVID-19 pandemic. Inclusions started on 30 March 2020 for 6 months. This study is proposed to all consecutive paediatric outpatients consulting during and after stay-at-home related to COVID-19 pandemic in medical-psychological centres and in a paediatric psychotrauma centre and/or calling the emergency COVID-19 hotline. We perform standardised and internationally validated psychiatric assessments (Diagnosis Infant and Preschool Assessment, Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version) together with anxiety, attention deficit hyperactivity disorder, PTSD, parenting stress and somatic symptoms scales during five visits (baseline, 1 week after baseline, 1 month after baseline, 1 week after the end of the containment and 1 month after the end of the containment) in patients and their families enrolled during the containment and during three visits in case of enrolment after the containment. The inclusion period will end in 30 November 2020. ETHICS AND DISSEMINATION: The protocol has been approved by the Ethics Committee of Cote d'Azur University « CERNI ¼ (number 2020-59). All patients and their legal caregivers provide a written informed consent on enrolment in the study. We will submit the results of the study to relevant journals and offer national and international presentations. This study will enable better characterisation of the impact of the stay-at-home (related to COVID-19 pandemic) on the mental health of children and adolescents. TRIAL REGISTRATION NUMBER: NCT04498416.

Analysis of Psychiatric Disorders by Age Among Children Following a Mass Terrorist Attack in Nice, France, on Bastille Day, 2016.

This cross-sectional study examines psychiatric disorders among children after a mass terrorist attack in Nice, France, in 2016.

Post-extinction fluoxetine treatment prevents stress-induced reemergence of extinguished fear.

RATIONALE: The post-extinction exposure of rats to a sub-conditioning procedure (SCP; i.e., retraining with a shock intensity that is too weak to induce by itself significant fear conditioning) has been reported to provoke the reemergence of extinguished fear. This phenomenon can be prevented by chronic fluoxetine treatment. OBJECTIVES: We sought to examine another potential inducer of fear reemergence, acute stress, in rats and determine whether fluoxetine prevents this phenomenon. METHODS: Because in previous studies fluoxetine was administered before extinction, we first analyzed its effect on the SCP-associated reemergence of auditory-cued conditioned fear in rats injected after extinction to avoid any interaction between fluoxetine and extinction learning. Next, we used the same protocol but replaced the SCP with acute stress. RESULTS: We found that the SCP and acute stress, which were carried out 3 weeks after fear extinction, similarly provoked the reemergence of extinguished fear in rats injected with vehicle during the 3-week period. In contrast, the animals treated with fluoxetine during this period behaved similarly to those not exposed to an inducer of fear reemergence. CONCLUSIONS: Our data establish acute stress as an inducer of fear reemergence. The results provide further support for the hypothesis that fluoxetine interfered with mechanisms that reactivated extinguished fear, even when administered after fear extinction.