Anxiety disorder | EPFL Graph Search

Anxiety disorders are a cluster of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal function are significantly impaired. Anxiety may cause physical and cognitive symptoms, such as restlessness, irritability, easy fatiguability, difficulty concentrating, increased heart rate, chest pain, abdominal pain, and a variety of other symptoms that may vary based on the individual. In casual discourse, the words anxiety and fear are often used interchangeably. In clinical usage, they have distinct meanings: anxiety is defined as an unpleasant emotional state for which the cause is either not readily identified or perceived to be uncontrollable or unavoidable, whereas fear is an emotional and physiological response to a recognized external threat. The umbrella term anxiety disorder refers to a number of specific disorders that include fears (phobias) or anxiety

In the pursuit of the fear engram: identification of neuronal circuits underlying the treatment of anxiety disorder

Ossama Mohamed Salah El-Dien El-Sayed Ibrahim Khalaf

Fear and other anxiety disorders are extraordinarily robust and difficult to treat. Among the most effective treatments for anxiety disorders are exposure-based therapies, during which a patient is repeatedly confronted with the originally fear-eliciting stimulus in a safe environment so that the once fearful stimulus can be newly interpreted as neutral or safe. A fundamental element for successful exposure-based therapies is the reactivation/recall of the traumatic memory, which initiates a time-limited process called memory reconsolidation, during which a memory becomes susceptible to disruption. Presently, the neuronal subpopulations and molecular mechanisms underlying successful fear memory attenuation remain completely unknown, which represents a big gap in memory research. Therefore, the aim of this work is to first identify the neuronal subpopulations that are causally implicated in effective attenuation of remote fear memories. This will help to determine whether the original traumatic memory trace has been permanently modified or a new memory trace of safety has been superimposed over the original one. The second aim is to develop a tool that allows for the isolation of the neuronal subpopulations causally implicated in remote memory attenuation, in order to be able to delineate the epigenetic and transcriptional mechanisms at play within these subpopulations. This will help to identify a molecular signature of effective remote fear memory attenuation. The results of my research suggest for the first time that there is a small population of neurons in the dentate gyrus - that was active during the recall of fear â that needs to be reactivated during extinction to attain successful remote fear attenuation. While the inactivation of such population during extinction impairs fear attenuation, its activation ameliorates behavioral extinction. Furthermore, I have successfully established a method to isolate this neuronal subpopulation from the brain, namely by fluorescence-activated cell sorting. This tool will allow follow up studies to pursue the quest for the molecular signature of successful remote memory attenuation. Overall, these findings could help us to better understand the intricate principles of effective remote fear memory attenuation, and thus to develop new strategies that improve the treatment of anxiety disorder.

EPFL2017

Role of the HPA axis in the long-term programming of social behaviors by peripuberty stress

Vandana Veenit

Stress during childhood and adolescence enhances the risk of psychopathology later in life. In fact, exposure to stress during this period is known to predispose individuals to the development of psychopathologies such as depression and anxiety disorders later in life. Similarly, individuals subjected to fearful experiences or abuse during childhood and puberty exhibit violent behaviors in adulthood, as revealed in both human literature and animal studies. Previous work from our laboratory has shown that exposing peripuberty rats to fear experiences (such as synthetic fox odor and exposure to an elevated platform) following an unpredictable schedule, on a range of 7 specific days across P28 to P42 in male Wistar rats leads to reduced sociability, increased aggression, anxiety- and depression-like behaviors in adulthood. The hypothalamic pituitary adrenal (HPA) axis is one of the main physiological stress systems and various components of the HPA axis like corticotropin releasing hormone (CRH), glucocorticoids are modulated in response to early life experience. We therefore sought to investigate the role of HPA axis in long term programming of social and emotional behaviors as a result of peripuberty stress(PPS). We addressed this by manipulating (i) glucocorticoid system by two approaches, and, (ii) corticotropin releasing hormone (CRH) system. First, using male Wistar rats, we evaluated the consequences of administration of corticosterone following the same experimental schedule as for stress administration in our peripuberty stress paradigm (without actual stress exposure) on play behavior on postnatal day 44 (P44) and on behavioral tests of anxiety, aggression, sociability and depression in adulthood. Corticosterone response to novelty was also measured in adulthood. Our results show that, as compared to vehicle-, corticosterone-treated animals exhibit higher aggressive play behavior during adolescence, and escalated aggressive behavior in adulthood, while reduced sociability and decreased corticosterone response to novelty in adulthood. No differences were observed between groups on anxiety- and depression-like behavior tested later in life. Next, we examined whether pharmacological blockade of glucocorticoid receptor 30 minutes prior to peripuberty stress would prevent the consequences of peripuberty stress on emotional, social behavior and dysregulated gene expression. Our findings showed that administration of glucocorticoid receptor antagonist on days of peripuberty stress prevents the effects of peripuberty stress on behaviors related to the domain of aggression and sociability in adulthood without producing any effect on anxiety- and depression-like behavior tested later in life. Interestingly, administration of GR antagonist in PPS animals also reversed the effects of PPS on increased expression of GR and Trpc5 genes in central nucleus of amygdala. We also observed increased Crhr1 expression in limbic areas in peripuberty stressed animals which was not reversed by administration of GR antagonist in peripuberty stressed animals. Subsequently, we sought to evaluate the consequences of counteracting CRHR1 activation during early post-stress period on long-term behavioral consequences of peripuberty stress in tests for anxiety- and depression-like behaviors. Our results showed that administration of CRHR1 antagonist post peripuberty stress rescued the effects of peripuberty stress on depression-like behavior and to some extent on anxiety- like behavior. Taken together, our studies show that corticosterone administration during peripuberty largely mimics the behavioral alterations observed in peripuberty stressed animals in social realm, administration of glucocorticoid receptor antagonist on days of peripuberty stress prevents the effects of peripuberty on social domain and on increased expression of GR and Trpc5 genes in central nucleus of amygdala, and administration of CRHR1 antagonist post peripuberty stress rescued the effects of PPS on depression-like behavior and to some extent on anxiety-like behavior.

EPFL2013

Interactions between Personality, Depression, Anxiety and Cognition to Understand Early Stage of Alzheimer's Disease

Valérie Rita Madeleine Zufferey

The multifaceted nature of Alzheimer's disease (AD) and Mild cognitive impairment (MCI) can lead to wide inter-individual differences in disease manifestation in terms of brain pathology and cognition. The lack of understanding of phenotypic diversity in AD arises from a difficulty in understanding the integration of different levels of network organization (i.e. genes, neurons, synapses, anatomical regions, functions) and in inclusion of other information such as neuropsychiatric characteristics, personal history, information regarding general health or subjective cognitive complaints in a coherent model. Non-cognitive factors, such as personality traits and behavioral and psychiatric symptoms, can be informative markers of early disease stage. It is known that personality can affect cognition and behavioral symptoms. The aim of the paper is to review the different types of interactions existing between personality, depression/anxiety, and cognition and cognitive disorders at behavioral and brain/genetic levels.

BENTHAM SCIENCE PUBL LTD2020