Pathological Fear Research Articles

Assessing primary Tokophobia among Lebanese childless men and nulliparous women: psychometric validation of the Arabic versions of the fathers’ fear of childbirth scale and Tokophobia severity scale

IntroductionTokophobia is an intense and pathological fear of pregnancy and childbirth. Despite its significance, no research in Lebanon has investigated primary tokophobia within the general population. Nevertheless, it is crucial to assess the attitudes of both women and men, as potential future parents, towards pregnancy and childbirth, particularly during these challenging times for the Lebanese population. Therefore, this study aims to evaluate the psychometric properties of the Tokophobia Severity Scale (TSS) and Fathers’ Fear of Childbirth Scale (FFCS) for assessing primary tokophobia among Lebanese nulliparous women and childless men, respectively.MethodsThis cross-sectional investigation encompassed all Lebanese governorates; 651 women and 618 men were recruited via social media platforms, using a snowball sampling technique. The questionnaire included the Tokophobia Severity Scale, the Fathers’ Fear of Childbirth Scale, the Patient Health Questionnaire, and the Lebanese Anxiety Scale.ResultsFactorial analysis of the TSS in women revealed a three-factor model: concerns related to personal complications (Factor 1), fetal well-being (Factor 2), and outward behavioral responses to fear (Factor 3). The FFCS also yielded a three-factor measurement model: emotional responses during the partner’s childbirth (Factor 1), concerns regarding the hospital environment during childbirth (Factor 2), and anxieties surrounding the perinatal health of both the partner and child (Factor 3). Both scales were internally consistent with Cronbach’s alpha > 0.9, indicating their reliability. The TSS and FFCS demonstrated statistically significant correlations with measures of anxiety and depression, thus attesting to convergent validity.ConclusionThe results of this study provide evidence for the psychometric validity and reliability of the TSS and FFCS scales in Arabic-speaking populations. Given the previously overlooked nature of primary tokophobia in these populations, the availability of these validated instruments can significantly enhance the ability to detect and address this condition, ultimately facilitating the provision of necessary support services.

Test anxiety as a risk factor for use of psychoactive compounds in medical students

<p><strong>Introduction. </strong>Test anxiety implies an intense pathological fear in situations of preparing and taking exams which is a significant problem for 15–70% of medical students. The frequent use of psychoactive substances is recognized as a problem for young people. The aim was to determine the frequency and degree of test anxiety and the association with misuse of psychoactive substances in medical students of the Faculty of Medicine in Foča.<br /><strong>Methods.</strong> The research was conducted according to the principle of a cross-sectional study at the Faculty of Medicine in Foča. Students were offered a custom-made questionnaire containing general and specific questions for test anxiety and use and dependence of psychoactive compounds and social networks. Test anxiety was evaluated by Westside anxiety scale. <br /><strong>Results.</strong> The sample included 145 respondents, 69.7% females and 30.3% males. The results indicate that the degree of test anxiety does not differ in male and female students, but test anxiety is less pronounced in younger students and students with medium academic success. The level of test anxiety was correlated with the rate of psychoactive compound use. Psychoactive substances were used by 50.3% of students, primary for anti-anxiety, than for psychostimulation and for hypnotic effects. The most commonly used classes of psychoactive substances were plant anxiolytics, followed by benzodiazepines, marijuana, alcohol and narcotics/cocaine (18.6%, 12.4%, 12.4%, 8.3%, and 4.8%, respectively).<br /><strong>Conclusion.</strong> A significant number of students reach for anxiolytics and other drugs that can create addiction. Elevated levels of test anxiety are positively correlated with increased consumption of psychoactive compounds. However, the frequency of use of psychoactive compounds surpasses the frequency of altogether moderate, high and extreme test anxiety.</p>

Sex differences in contextual fear expression are associated with altered medial prefrontal cortex activity.

Understanding the neural basis of fear expression in rodents has implications for understanding pathological fear responses that characterize posttraumatic stress disorder. Even though posttraumatic stress disorder is more common in females, little is known about the neural circuit interactions supporting fear expression in female rodents. In this study, we were interested in determining whether neural activity associated with the expression of contextual fear differed between males and females within the projections from the medial prefrontal cortex to the ventrolateral periaqueductal gray, and in the medial prefrontal cortex in neurons that do not project to the periaqueductal gray. We infused a viral retrograde tracer into the ventrolateral periaqueductal gray in male and female rats and trained them in a contextual fear conditioning task. The following day rats were re-exposed to the conditioning context and were sacrificed shortly thereafter. Neural activity was measured using EGR1 immunofluorescence. The behavioral results showed that males exhibited higher levels of freezing during the context test than females. Male rats that underwent training and testing showed an increase in the proportion of viral infected cells that express EGR1 in the PL compared to rats that had only received context exposure. Trained female rats were not different than controls, however a direct comparison between sexes was not different. In cells not labeled by the tracer, males showed higher levels of fear-induced EGR1 expression in the prelimbic cortex than females. Conversely, females showed higher levels of EGR1 expression in the infralimbic cortex following testing as compared to males. These results suggest that sex differences in the expression of contextual fear may involve differences in the relative activity levels of the prelimbic and infralimbic cortex.

Burden and Coping Strategies of Hypoglycemia in People with Diabetes.

Hypoglycemia is a limiting adverse effect of glucose-lowering medications and particularly insulin replacement therapy. This review provides insights into the burden of hypoglycemia in the management of diabetes and outlines strategies available to reduce the risk of hypoglycemia and improve patients' well-being. People with type 1 diabetes are primarily affected by hypoglycemic episodes which are associated with direct physical harms like injuries and cardiac events as well as indirect psychosocial consequences including constant anxiety, absenteeism, increased healthcare costs and overall poorer quality of life. These complications are more prominent amongst individuals with hypoglycemia unawareness or overnight hypoglycemia and could even extend to caregivers such as parents of children with diabetes. Patients experiencing frequent or severe hypoglycemic events might also develop a pathological fear of hypoglycemia and adopt aberrant behaviors intending to maintain higher blood glucose levels. Modern pharmaceutical options with a safer profile in terms of hypoglycemia are available including novel basal insulins with lower rates of nocturnal hypoglycemia along with ultra-rapid-acting insulin analogs with a shorter duration of action that might avert late post-meal hypoglycemia. Continuous glucose monitoring and sensor-augmented insulin pump therapy with low glucose suspend technology can also prevent hypoglycemia, although concerns about cost and patient satisfaction remain. Advancements in insulin therapy and technological modalities should be coupled with ongoing education and support for patients to become co-managers of their disease and reduce the risk of hypoglycemia.

Tokophobia and Domestic Violence: The Pathological Fear of Pregnancy and Childbirth.

Tokophobia and Domestic Violence: The Pathological Fear of Pregnancy and Childbirth.

Anticipatory anxiety of seizures in epilepsy: A common, complex, and underrecognized phenomenon?

The diagnosis of epilepsy is associated with loss of predictability, which invariably results in the fear of when and if future seizures will occur. For a subset of patients with epilepsy (PWE), there may be a pathological persistent fear of seizure occurrence, resulting in limitations to daily activities through avoidant behaviors. Paradoxically, the research of anticipatory anxiety of seizures (AAS; also referred to as seizure phobia) has been practically nonexistent and, not surprisingly, this condition remains underrecognized by clinicians. The available data are derived from three small case series of patients followed in tertiary epilepsy centers. In this study, we review the available data on the reported clinical manifestations of AAS in PWE, and of the potential role of variables associated with it, such as personal and family psychosocial and psychiatric history and epilepsy-related variables. In addition, we review the need for the creation of screening tools to identify patients at risk of AAS and discuss potential treatment strategies, which could be considered as part of the comprehensive management for PWE.

Neurobiology and systems biology of stress resilience.

Stress resilience is the phenomenon that some people maintain their mental health despite exposure to adversity or show only temporary impairments followed by quick recovery. Resilience research attempts to unravel the factors and mechanisms that make resilience possible and to harness its insights for the development of preventative interventions in individuals at risk for acquiring stress-related dysfunctions. Biological resilience research has been lagging behind the psychological and social sciences but has seen a massive surge in recent years. At the same time, progress in this field has been hampered by methodological challenges related to finding suitable operationalizations and study designs, replicating findings, and modeling resilience in animals. We embed a review of behavioral, neuroimaging, neurobiological, and systems biological findings in adults in a critical methods discussion. We find preliminary evidence that hippocampus-based pattern separation and prefrontal-based cognitive control functions protect against the development of pathological fears in the aftermath of singular, event-type stressors [as found in fear-related disorders, including simpler forms of posttraumatic stress disorder (PTSD)] by facilitating the perception of safety. Reward system-based pursuit and savoring of positive reinforcers appear to protect against the development of more generalized dysfunctions of the anxious-depressive spectrum resulting from more severe or longer-lasting stressors (as in depression, generalized or comorbid anxiety, or severe PTSD). Links between preserved functioning of these neural systems under stress and neuroplasticity, immunoregulation, gut microbiome composition, and integrity of the gut barrier and the blood-brain barrier are beginning to emerge. On this basis, avenues for biological interventions are pointed out.

Identification of a novel perifornical-hypothalamic-area-projecting serotonergic system that inhibits innate panic and conditioned fear responses

The serotonin (5-HT) system is heavily implicated in the regulation of anxiety and trauma-related disorders such as panic disorder and post-traumatic stress disorder, respectively. However, the neural mechanisms of how serotonergic neurotransmission regulates innate panic and fear brain networks are poorly understood. Our earlier studies have identified that orexin (OX)/glutamate neurons within the perifornical hypothalamic area (PFA) play a critical role in adaptive and pathological panic and fear. While site-specific and electrophysiological studies have shown that intracranial injection and bath application of 5-HT inhibits PFA neurons via 5-HT1a receptors, they largely ignore circuit-specific neurotransmission and its physiological properties that occur in vivo. Here, we investigate the role of raphe nuclei 5-HT inputs into the PFA in panic and fear behaviors. We initially confirmed that photostimulation of glutamatergic neurons in the PFA of rats produces robust cardioexcitation and flight/aversive behaviors resembling panic-like responses. Using the retrograde tracer cholera toxin B, we determined that the PFA receives discrete innervation of serotonergic neurons clustered in the lateral wings of the dorsal (lwDRN) and in the median (MRN) raphe nuclei. Selective lesions of these serotonergic projections with saporin toxin resulted in similar panic-like responses during the suffocation-related CO2 challenge and increased freezing to fear-conditioning paradigm. Conversely, selective stimulation of serotonergic fibers in the PFA attenuated both flight/escape behaviors and cardioexcitation responses elicited by the CO2 challenge and induced conditioned place preference. The data here support the hypothesis that PFA projecting 5-HT neurons in the lwDRN/MRN represents a panic/fear-off circuit and may also play a role in reward behavior.

Tokophobia—Extreme Fear of Pregnancy and Birth and Implications for Care: A Case Report

The extreme or pathological fear of pregnancy and childbirth, also known as tokophobia, was first described in the mid-to-late 1800s but then rarely discussed in the literature until the turn of the 21st century. However, information remains scarce. Therefore, the goals of this case study are to describe the clinical presentation and management options of extreme fear of pregnancy and/or birth. The patient in our study is from the United States. She presented with tokophobia at her first prenatal appointment, requesting a cesarean surgery immediately, but experienced discontinuous care throughout her pregnancy. She became frustrated by the need to repeat her desire for a cesarean surgery and eventually was verbally disruptive at her 38-week visit, crying and yelling at providers and staff. If this patient had received continuous care and earlier intervention and education, her pregnancy may have been a more positive experience. This case highlights the importance of establishing a standard of care for women with tokophobia and then adapting that standard to fit each woman’s individual needs.

Approbation of the Methodology for Studying the Frequency and Intensity of Existential Fears in Adolescents 15–17 years’ Old

Introduction. The article deals with the problem of the growth of high-intensity fears among adolescents over the past year, and their identification with the help of its own psychodiagnostic technique. The study fills the lack of scientific works on studying the manifestation of fears in adolescents of the older age group.Purpose. To carry out approbation of the author's questionnaire-questionnaire "Peculiarities of actualization of existential fears of a personality", consisting of closed and open-ended questions, taking into account the difference between this methodology and other methods aimed at studying actual fears of a personality.Materials and Methods. The study was conducted with the involvement of high school students as respondents, a total of 98 people took part in the study. As a result of the study it was found that all boys and girls aged 15-17 have fears, but their distribution in terms of number, frequency and intensity differs in different gender groups. To confirm the adequacy of the integrative indicator "fear intensity", the methods "Life Satisfaction Scale" and "Death Anxiety Scale" were used. The Mann-Whitney U-criterion was used to confirm the reliability of differences between groups.Results. Content analysis of the open questions of the author's questionnaire-questionnaire made it possible to identify factors influencing the emergence and development of fears, their frequency and intensity, ways to overcome fears and understanding of the negative impact of high-intensity frequent fears by adolescents, as well as their need for professional psychological help.Discussion. This technique can be used as a screening tool to identify the frequency and intensity of fears in different gender and age groups, used for different purposes, including the identification of persons in need of further psychologically corrective work, which will prevent the development of existential fears of high intensity or reduce the intensity of these fears, which, in turn, will help to avoid distress associated with pathological fears, leading to possible personality maladaptation.

Award for Distinguished Scientific Contributions: Michael S. Fanselow.

The APA Award for Distinguished Scientific Contributions honors psychologists who have made distinguished theoretical or empirical contributions to basic research in psychology. "For his systematic and integrative research on the neural and behavioral mechanisms of Pavlovian fear learning. Guided by a functional behavior perspective, Michael S. Fanselow's pioneering studies of conditioned analgesia describe a fundamental biological mechanism for regulating associative learning through error correction. His analysis of the organization of defensive behavior in relation to predatory imminence has yielded a novel theoretical framework for understanding fear, anxiety, and panic. His research has revealed an essential neural architecture for fear conditioning that not only informs how we understand normal and pathological fear but also demonstrates how rigorous neural and behavioral approaches enrich and strengthen one another." (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Thalamic nucleus reuniens coordinates prefrontal-hippocampal synchrony to suppress extinguished fear

Traumatic events result in vivid and enduring fear memories. Suppressing the retrieval of these memories is central to behavioral therapies for pathological fear. The medial prefrontal cortex (mPFC) and hippocampus (HPC) have been implicated in retrieval suppression, but how mPFC-HPC activity is coordinated during extinction retrieval is unclear. Here we show that after extinction training, coherent theta oscillations (6–9 Hz) in the HPC and mPFC are correlated with the suppression of conditioned freezing in male and female rats. Inactivation of the nucleus reuniens (RE), a thalamic hub interconnecting the mPFC and HPC, reduces extinction-related Fos expression in both the mPFC and HPC, dampens mPFC-HPC theta coherence, and impairs extinction retrieval. Conversely, theta-paced optogenetic stimulation of RE augments fear suppression and reduces relapse of extinguished fear. Collectively, these results demonstrate a role for RE in coordinating mPFC-HPC interactions to suppress fear memories after extinction.

Association of demographic characteristics with mental anxiety caused by the spread of the COVID-19 pandemic in candidate patients for cataract surgery

Introduction: The increasing outbreak of COVID-19 disease has challenged global public health and caused a pathological fear of its contracting. The unknown origin of COVID-19, long incubation period, high death rate, rapid transmissions, and the lack of definitive or preventive treatment caused great fear and anxiety among the world population. Objectives: This study aimed to evaluate the correlation between demographic characteristics and mental anxiety caused by the COVID-19 pandemic among candidate patients for cataract surgery. Patients and Methods: This descriptive-analytical study selected 258 candidates for cataract surgery patients referred to Shahid Dastgheib and Khalili hospitals in Shiraz. The data were collected using a demographic and the Corona Disease Anxiety Scale questionnaire. Analytical tests were used for data analysis, including Mann-Whitney U, Spearman’s correlation, Kruskal-Wallis, and univariate and multivariate linear regression. Results: Most participants were women with a mean age of 62.8 ± 15.9 years. There was no statistically significant correlation between age, education level, and history of COVID-19 with mental anxiety (P > 0.001). In contrast, gender and job indicated a statistically significant correlation. Housewives and retired people experienced higher levels of mental anxiety (P < 0.001). Multivariate linear regression explored that amongst all demographic characteristics, only female gender was an independent risk factor for patients’ mental anxiety. Conclusion: Considering the mental health of patients applying for surgery by gender status during the COVID-19 pandemic is very important.

Postsynaptic histamine H3 receptors in ventral basal forebrain cholinergic neurons modulate contextual fear memory

Overly strong fear memories can cause pathological conditions. Histamine H3 receptor (H3R) has been viewed as an optimal drug target for CNS disorders, but its role in fear memory remains elusive. We find that a selective deficit of H3R in cholinergic neurons, but not in glutamatergic neurons, enhances freezing level during contextual fear memory retrieval without affecting cued memory. Consistently, genetically knocking down H3R or chemogenetically activating cholinergic neurons in the ventral basal forebrain (vBF) mimics this enhanced fear memory, whereas the freezing augmentation is rescued by re-expressing H3R or chemogenetic inhibition of vBF cholinergic neurons. Spatiotemporal regulation of H3R by a light-sensitive rhodopsin-H3R fusion protein suggests that postsynaptic H3Rs in vBF cholinergic neurons, but not presynaptic H3Rs of cholinergic projections in the dorsal hippocampus, are responsible for modulating contextual fear memory. Therefore, precise modulation of H3R in a cell-type- and subcellular-location-specific manner should be explored for pathological fear memory.

Early- and late-phase changes of brain activity and early-phase neuromodulation in the posttraumatic stress disorder rat model

Posttraumatic stress disorder (PTSD) is a complex syndrome that may occur after life-threatening events. Fear memory abnormalities may play vital roles in the pathogenesis of PTSD. Previous work has found that fear memories are not rigid; the retrieval of fear memories may change over time. Furthermore, prior studies suggest that theta wave (4 Hz) activity is highly correlated with fear expression in an animal model. However, the relationship between pathological fear memory and potential brain wave features in PTSD remains largely uncharacterized. Here, we hypothesized that after traumatic stress exposure, the longitudinal dynamics of abnormal fears in PTSD animal models could be reflected by the measurement of local field potentials (LFPs). Using a well-established modified single-prolonged stress and footshock (SPS & FS) PTSD rat model, animals were restrained for 2 h and subsequently subjected to 20 min of forced swimming, then exposed to diethyl ether until they lost consciousness and placed in a conditioning chamber for fear conditioning. To characterize the temporal changes, we characterized freezing behavior brain wave features during the conditioning chamber re-exposure in the early (10 and 30 min; 2, 4, and 6 h) and late (day 1, 3, 7, and 14) phases after traumatic stress exposure. Our results indicate that SPS & FS rats showed co-morbid PTSD phenotypes including significantly higher levels of anxiety-, depression-, and anhedonia-like behaviors, and impaired fear extinction. Delta wave (0.5–4 Hz) suppression in the medial prefrontal cortex, amygdala, and ventral hippocampus occurred 10 and 30 min after traumatic stress, followed by continuous delta wave activity from 2 h to day 14, correlating with fear levels. tDCS reduced delta activity and alleviated PTSD-like phenotypes in the SPS & FS group. In this study, profiling abnormal fears with brain wave correlates may improve our understanding of time-dependent pathological fear memory retrieval in PTSD and facilitate the development of effective intervention strategies.

Closed-loop brain stimulation augments fear extinction in male rats

Dysregulated fear reactions can result from maladaptive processing of trauma-related memories. In post-traumatic stress disorder (PTSD) and other psychiatric disorders, dysfunctional extinction learning prevents discretization of trauma-related memory engrams and generalizes fear responses. Although PTSD may be viewed as a memory-based disorder, no approved treatments target pathological fear memory processing. Hippocampal sharp wave-ripples (SWRs) and concurrent neocortical oscillations are scaffolds to consolidate contextual memory, but their role during fear processing remains poorly understood. Here, we show that closed-loop, SWR triggered neuromodulation of the medial forebrain bundle (MFB) can enhance fear extinction consolidation in male rats. The modified fear memories became resistant to induced recall (i.e., ‘renewal’ and ‘reinstatement’) and did not reemerge spontaneously. These effects were mediated by D2 receptor signaling-induced synaptic remodeling in the basolateral amygdala. Our results demonstrate that SWR-triggered closed-loop stimulation of the MFB reward system enhances extinction of fearful memories and reducing fear expression across different contexts and preventing excessive and persistent fear responses. These findings highlight the potential of neuromodulation to augment extinction learning and provide a new avenue to develop treatments for anxiety disorders.

Epistemic agency and the generalisation of fear

Fear generalisation is a psychological phenomenon that occurs when fear that is elicited in response to a frightening stimulus spreads to similar or related stimuli. The practical harms of pathological fear generalisation related to trauma are well-documented, but little or no attention has been given so far to its epistemic harms. This paper fills this gap in the literature. It shows how the psychological phenomenon, when it becomes pathological, substantially curbs the epistemic agency of those who experience the fear that generalizes, limiting their ability to respond to evidence, and substantially limiting their epistemic horizons. It is argued that when these epistemic harms are caused by wrongful actions and decisions of individuals or institutions, because the fear is elicited in response to a traumatic experience inflicted by them, the harms should be considered epistemic wrongs. The epistemic wrongs are closely akin to agential epistemic injustice, a variety of distributive epistemic injustice, and sometimes also involve epistemic exclusion. The paper thereby identifies a previously underexplored psychological mechanism that can be a vehicle through which both individuals and institutions can epistemically wrong others. The argument has implications for how both epistemic wrongs and epistemic injustice should be conceived, suggesting that both can occur without being caused by primarily epistemic flaws or errors, or a bad epistemic character. Finally, it highlights the advantage of taking a victim-centred approach to understanding epistemic harm.

Case report of tokophobia

Introduction: Tokophobia is a pathological fear of pregnancy that can lead to avoidance of childbirth. It is classified as primary or secondary. Approximately 20% to 78% of pregnant women report fears associated with pregnancy and childbirth. This report describes a patient with tokophobia: presentation, risk factors, comorbidities, and treatment. Case presentation: A 43-year-old Saudi woman experienced tokophobia upon becoming pregnant for the fifth time. She was assessed in 2 clinical interviews by a consultant psychiatrist specializing in women’s mental health. In addition, she completed several questionnaires that aimed to assess different aspects of her mental health: overall depression, perinatal depression, generalized anxiety, maternal functioning, and fear of childbirth. Several risk factors and comorbidities that may have contributed to the development of tokophobia in this patient were discussed, including traumatic experiences in previous deliveries, the unplanned nature of the pregnancy, perinatal depression, and pronounced symptoms of anxiety. A collaborative decision to perform a C-section was made, in line with obstetric guidelines and good mental health practices. Full symptomatic recovery was achieved immediately after delivery. Conclusion: We hope to increase clinical awareness of the assessment and management of tokophobia, which is a relatively new concept and, as yet, understudied.

Impact of Midwife-Led Psychoeducation on Primigravida Mothers’ Knowledge of Childbirth Fear and Childbirth Efficiency: A Review

Childbirth, often known as labor and delivery, is the procedure that ends a pregnancy and takes place when one or more infants are delivered vaginally or through cesarean section from the mother’s body. Primigravidae experience several physical and emotional changes, which can make them nervous about the birthing process. The pathological fear of pregnancy known as “childbirth fear” is one factor that can contribute to a woman delaying her delivery. It has been found that a woman’s level of childbirth self-efficacy, which is also referred to as labor and delivery confidence, is a crucial indicator of how well she will be able to cope with the physical and emotional challenges that come with giving birth. Prenatal education, prenatal counseling, prenatal training, and role-playing are all examples of psychoeducational intervention techniques that have been shown to have a significant impact on a variety of psychological outcomes, including attitudes toward childbirth, fears associated with childbirth, depression, fear, and anxiety. Their expectations for the birth procedure were elevated as a result of solutionfocused counseling, midwife-supported psychotherapy, and a midwife-led integrated pre-birth training program.

Long-lasting BDNF signaling alterations in the amygdala of adolescent female rats exposed to the activity-based anorexia model.

Introduction: Anorexia nervosa (AN) is a severe psychiatric disorder characterized by a pathological fear of gaining weight, excessive physical exercise, and emotional instability. Since the amygdala is a key region for emotion processing and BDNF has been shown to play a critical role in this process, we hypothesized that alteration in the amygdalar BDNF system might underline vulnerability traits typical of AN patients. Methods: To this end, adolescent female rats have been exposed to the Activity-Based Anorexia (ABA) protocol, characterized by the combination of caloric restriction and intense physical exercise. Results: The induction of the anorexic phenotype caused hyperactivity and body weight loss in ABA animals. These changes were paralleled by amygdalar hyperactivation, as measured by the up-regulation of cfos mRNA levels. In the acute phase of the pathology, we observed reduced Bdnf exon IX, exon IV, and exon VI gene expression, while mBDNF protein levels were enhanced, an increase that was, instead, uncoupled from its downstream signaling as the phosphorylation of TrkB, Akt, and S6 in ABA rats were reduced. Despite the body weight recovery observed 7 days later, the BDNF-mediated signaling was still downregulated at this time point. Discussion: Our findings indicate that the BDNF system is downregulated in the amygdala of adolescent female rats under these experimental conditions, which mimic the anorexic phenotype in humans, pointing to such dysregulation as a potential contributor to the altered emotional processing observed in AN patients. In addition, since the modulation of BDNF levels is observed in other psychiatric conditions, the persistent AN-induced changes of the BDNF system in the amygdala might contribute to explaining the onset of comorbid psychiatric disorders that persist in patients even beyond recovery from AN.