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. 2002 Sep;4(3):231-49.
doi: 10.31887/DCNS.2002.4.3/tsteimer.

The biology of fear- and anxiety-related behaviors

Affiliations

The biology of fear- and anxiety-related behaviors

Thierry Steimer. Dialogues Clin Neurosci. 2002 Sep.

Abstract

Anxiety is a psychological, physiological, and behavioral state induced in animals and humans by a threat to well-being or survival, either actual or potential. It is characterized by increased arousal, expectancy, autonomic and neuroendocrine activation, and specific behavior patterns. The function of these changes is to facilitate coping with an adverse or unexpected situation. Pathological anxiety interferes with the ability to cope successfully with life challenges. Vulnerability to psychopathology appears to be a consequence of predisposing factors (or traits), which result from numerous gene-environment interactions during development (particularly during the perinatal period) and experience (life events), in this review, the biology of fear and anxiety will be examined from systemic (brain-behavior relationships, neuronal circuitry, and functional neuroanatomy) and cellular/molecular (neurotransmitters, hormones, and other biochemical factors) points of view, with particular reference to animal models. These models have been instrumental in establishing the biological correlates of fear and anxiety, although the recent development of noninvasive investigation methods in humans, such as the various neuroimaging techniques, certainly opens new avenues of research in this field. Our current knowledge of the biological bases of fear and anxiety is already impressive, and further progress toward models or theories integrating contributions from the medical, biological, and psychological sciences can be expected.

La ansiedad es una condición psicológica, fisiológica y conductual que se induce en los animales y en el hombre por una amenaza al bienestar o a la sobrevivencia, sea presente o potencial. Se caracteriza por un aumento del alerta, expectación, activación autonómica y endocrina, y patrones conductuales específicos. La función de estes cambios es facilitar la adaptación ante una situatión adversa o inesperada. La ansiedad patológica interfiere con la capacidad para adaptarse exitosamente a los desafíos de la vida. La vulnerabilidad a la psicopatología parece ser una consecuencia de factores predisponentes (o rasgos) los cuales se deben a numerosas interacciones entre los genes y el ambiente durante el desarrollo (especialmente durante el período perinatal) y a lo largo del curso de la vida (acontecimientos vitales). En esta revisión se examinará la biología del miedo y la ansiedad desde aproximaciones sistémicas (relaciones cerebro-conducta, circuitos neuronales y neuroanatomía funcional) y moleculares/celulares (neurotransmisores, hormonas y otros factores bioquímicos) poniendo especial atención a los modelos animales. Estos modelos han constituido un medio para establecer los correlatos biológicos del miedo y la ansiedad; sin embargo, el reciente desarrollo de métodos de investigación no invasores en humanos, como las diversas técnicas de neuroimágenes, ciertamente abre nuevas vías de investigación en este campo. Nuestro conocimíento actual de las bases biológicas del miedo y la ansiedad ya es notable y se puede esperar que a futuro se progrese hacia modelos o teorías que integren contribuciones desde las ciencias médicas, biológicas y psicológicas.

L'anxiété est un état psychologique, physiologique et comportemental provoqué chez les animaux et les humains par une menace qui s'exerce sur le bien-être ou la survie, qu'elle soit réelle ou potentielle. Elle est caractérisée par une hypervigilance, une attente excessive, une activation des systèmes autonome et neuroendocrine et par des schémas comportementaux spécifiques. Ces modifications doivent faciliter l'adaptation à une situation hostile ou inattendue. L'anxiété pathologique interfère avec la capacité de s'adapter avec succès aux aléas de la vie. La susceptibilité à la psychopathologie semble résulter de facteurs prédisposants (ou de caractères), eux-mêmes issus de nombreuses interactions gène-environnement pendant la phase de développement (particulièrement durant la période périnatale) et de l'expérience (événements de la vie). Dans cet article, la biologie de la peur et de l'anxiété sera examinée d'un point de vue systémique (relations cerveau-comportement, circuits neuronaux et neuroanatomie fonctionnelle) et d'un point de vue cellulaire et moléculaire (neurotransmetteurs, hormones et autres facteurs biochimiques), avec une référence particulière aux modèles animaux. Ces modèles ont contribué à l'établissement de corrélations biologiques de la peur et de l'anxiété, bien que les avancées récentes des méthodes d'investigation non invasives chez les humains, telles les diverses techniques de neuro-imagerie, ouvrent certainement de nouvelles voies de recherche dans ce domaine. Nos connaissances actuelles des bases biologiques de la peur et de l'anxiété sont déjà impressionnantes et nous pouvons espérer des progrès supplémentaires de la part de modèles ou de théories intégrant les données des sciences médicales, biologiques et psychologiques.

Keywords: animial models; anxiety; behavior; emotions; fear; neurobiology.

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Figures

Figure 1.
Figure 1.. A schematic view of major brain circuits involved in fear and anxiety. External auditory, visual, olfactory, or somatosensory stimuli are relayed by the thalamus to the amygdala and cortex. The basolateral complex (BLA) of the amygdala is the input side of the system, which also receives contextual information from the hippocampal formation (entorhinal cortex, hippocampus, and ventral subiculum). After intra-amygdala processing of the emotional stimuli, the central nucleus of the amygdala (CeA), on the output side, activates the locus ceruleus (LC) and central and peripheral noradrenaline systems (via corticotropin-releasing factor [CRF] neurons), and the hypothalamus (paraventricular nucleus [PVN] and lateral hypothalamus [LH]). The bed nucleus of the stria terminalis (BNST, part of the “extended amygdala”) is also a control center for the neuroendocrine system by integrating information originating from both the hippocampus and the amygdala. In addition, the CeA directly activates various midbrain regions or nuclei responsible for different aspects of the fear/anxiety response: freezing or escape (periaqueductal gray [PAG]), increased respiratory rate (parabrachial nucleus [PBN]), startle (caudal reticulopontine nucleus of the reticular formation [RPC]), and the dorsal motor nucleus of the vagus (DMN) in the medulla, which (together with the lateral hypothalamus) is responsible for the increase in heart rate and blood pressure associated with emotional events. The prefrontal cortex (PFC) processes more elaborate (“cognitive”) information; it modulates the physiological, neuroendocrine, and behavioral responses (via the amygdala), and it is also involved in the extinction of fear- and anxiety-related conditional responses. ACTH, adrenocorticotropic hormone; ANS, autonomous nervous system; BP, blood pressure; GABA, β-aminobutyric acid; Glu, glutamate; NA, noradrenaline (neurotransmitter) or nucleus ambiguus (structure); NTS, nucleus tractus solitarius.

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