Abstract
Recent advances in basic and clinical research in the anxiety disorders converge on several areas: (1) critically distinguishing clinical features of these disorders; (2) the neurobiological basis of anxiety disorders in human populations; (3) animal studies that define cause–effect relations between neural function and anxiety or fear behaviors; and (4) studies of etiology that provide an increasingly clear understanding of the developmental trajectories that define vulnerability for anxiety disorders. Additionally, emerging areas of research are studies of behavior, cognitive function, and neural activity in clinical populations to define the clinically relevant effects of pharmacological and psychotherapeutic treatments. This chapter summarizes and synthesizes current research approaches to anxiety disorders, and attempts to show the impact of this research on current trends in their diagnosis and treatment. Currently, there is increasing emphasis on relevant clinical dimensions, as opposed to more traditional categorical approaches, and an emerging view of anxiety as a set of cognitive–perceptual disorders that derives from alterations in neural systems critical for attentional processes and emotional regulation.
This chapter is an update from the 4th edition. Previous edition authors were Michael J. Meaney, Michael L. Liebowitz and E. David Leonardo
This is a preview of subscription content, log in via an institution to check access.
References
Adamec, R., Walling, S., & Burton, P. (2004). Long-lasting, selective, anxiogenic effects of feline predator stress in mice. Physiology and Behavior, 83, 401–410.
Adamec, R. E., Blundell, J., & Burton, P. (2006). Relationship of the predatory attack experience to neural plasticity, pCREB expression and neuroendocrine response. Neuroscience and Biobehavioral Reviews, 30, 356–375.
Aguilar, R., Gil, L., Fernandez-Teruel, A., et al. (2004). Genetically-based behavioral traits influence the effects of Shuttle Box avoidance overtraining and extinction upon intertrial responding: a study with the Roman rat strains. Behavioural Processes, 66, 63–72.
Ahmari, S. E., Spellman, R., Douglass, N. L., et al. (2013). Repeated cortiostriatal stimulation generates persistent OCD-like behavior. Science, 6137, 1234–1239.
Albelda, N., & Joel, D. (2012). Animal models of obsessive-compulsive disorder: exploring pharmacology and neural substrates. Neuroscience and Biobehavioral Reviews, 36(1), 47–63.
Amat, J., Baratta, M. V., Paul, E., et al. (2005). Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus. Nature Neuroscience, 8, 365–371.
American Psychiatric Association. (1952). Diagnostic and statistical manual of mental disorders. (DSM-I) (1st ed.). American Psychiatric Press.
American Psychiatric Association. (1968). Diagnostic and statistical manual of mental disorders. (DSM-II) (2nd ed.). American Psychiatric Press.
American Psychiatric Association. (1980). Diagnostic and statistical manual of mental disorders. (DSM-III) (3rd ed.). American Psychiatric Press.
American Psychiatric Association. (1987). Diagnostic and statistical manual of mental disorders. Revised (DSM-III-R) (3rd ed.). American Psychiatric Press.
American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders. (DSM-IV) (4th ed.). American Psychiatric Press.
American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders. (DSM-5) (5th ed.). American Psychiatric Publishing.
Anacker, C., & Hen, R. (2017). Adult hippocampal neurogenesis and cognitive flexibility – linking memory and mood. Nature Reviews. Neuroscience, 18(6), 335–346.
Anacker, C., et al. (2018). Hippocampal neurogenesis confers stress resilience by inhibiting the ventral dentate gyrus. Nature, 559, 98–102.
Andreatini, R., & Bacellar, L. F. (2000). Animal models: Trait or state measure? The test-retest reliability of the elevated plus-maze and behavioral despair. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 24, 549–560.
Andrews, G., Stewart, G., Allen, R., et al. (1990). The genetics of six neurotic disorders: A twin study. Journal of Affective Disorders, 19, 23–29.
Arbelle, S., Benjamin, J., Golin, M., et al. (2003). Relation of shyness in grade school children to the genotype for the long form of the serotonin transporter promoter region polymorphism. American Journal of Psychiatry, 160(4), 671–676.
Asendorpf, J. B., Denissen, J. J., & van Aken, M. A. (2008). Inhibited and aggressive preschool children at 23 years of age: Personality and social transitions into adulthood. Developmental Psychology, 44(4), 997–1011.
Auerbach, J. G., Faroy, M., Ebstein, R., et al. (2001). The association of the dopamine D4 receptor gene (DRD4) and the serotonin transporter promoter gene (5-HTTLPR) with temperament in 12-month-old infants. Journal of Child Psychology and Psychiatry and Allied Disciplines, 42(6), 777–783.
Baratta, M. V., Gruene, T. M., Dolzani, S. D., Chun, L. E., Maier, S. F., & Shansky, R. M. (2019). Controllable stress elicits circuit-specific patterns of prefrontal plasticity in males, but not females. Brain Structure & Function, 224(5), 1831–1843.
Barr, C. S., Newman, T. K., Shannon, C., et al. (2004). Rearing condition and rh5-HTTLPRinteract to influence limbic-hypothalamic-pituitary-adrenal axis response to stress in infant macaques. Biological Psychiatry, 55, 733–738.
Bear, M. F. (1996). A synaptic basis for memory storage in the cerebral cortex. Proceedings of the National Academy of Sciences of the United States of America, 93, 13453–13459.
Beesdo, K., Knappe, S., & Pine, D. S. (2009). Anxiety and anxiety disorders in children and adolescents: Developmental issues and implications for DSM-V. The Psychiatric Clinics of North America, 32(3), 483–524.
Belsky, J. (1997). Variation in susceptibility to rearing influence: An evolutionary argument. Psychological Inquiry, 8, 182–186.
Belsky, J., Hsieh, K., & Crnic, K. (1998). Mothering, fathering, and infant negativity as antecedents of boys’ externalizing problems and inhibition at age 3: differential susceptibility to rearing influence? Development and Psychopathology, 10, 301–319.
Bennett, A. J., Lesch, K. P., Heils, A., et al. (2002). Early experience and serotonin transporter gene variation interact to influence primate CNS function. Molecular Psychiatry, 7, 118–122.
Biederman, J., Hirshfeld-Becker, D. R., Rosenbaum, J. F., et al. (2001). Further evidence of association between behavioral inhibition and social anxiety in children. American Journal of Psychiatry, 158, 1673–1679.
Blair, C. (2002). Early intervention for low birth weight preterm infants: The role of negative emotionality in the specification of effects. Development and Psychopathology, 14(2), 311–332.
Blanchard, C. D., Hynd, A. L., Minke, K. A., et al. (2001). Human defensive behaviors to threat scenarios show parallels to fear- and anxiety-related defense patterns of non-human mammals. Neuroscience and Biobehavioral Reviews, 25, 761–770.
Blier, P. (2001). Crosstalk between the norepinephrine and serotonin systems and its role in the antidepressant response. Journal of Psychiatry and Neuroscience, 26(Suppl), S3–S10.
Bodnoff, S. R., Suranyi-Cadotte, B. E., Quirion, R., et al. (1989). Role of the central benzodiazepine receptor system in behavioral habituation to novelty. Behavioral Neuroscience, 103(1), 209–212.
Bouton, M. E., & Bolles, R. C. (1979). Contextual control of the extinction of conditioned fear. Learning and Motivation, 10, 455–466.
Bouton, M. E., & King, D. A. (1983). Contextual control of the extinction of conditioned fear tests for the associative value of the context. Journal of Experimental Psychology: Animal Behavior Processes, 9, 248–265.
Bouton, M. E., Kenney, F. A., & Rosengard, C. (1990). State-dependent fear extinction with two benzodiazepine tranquilizers. Behavioral Neuroscience, 104, 44–55.
Bowlby, J. (1960). The making and breaking of affectional bonds. British Journal of Psychiatry, 130, 201–210.
Bredy, T. W., Zhang, T.-Y., Grant, R. J., et al. (2004). Peripubertal environmental enrichment reverses the effects of maternal care on hippocampal development and glutamate receptor subunit expression. European Journal of Neuroscience, 20, 1355–1362.
Breiter, H. C., Etcoff, N. L., Whalen, P. J., et al. (1996). Response and habituation of the human amygdala during visual processing of facial expression. Neuron, 17, 875–887.
Bremner, J. D., Staib, L. H., Kaloupek, D., et al. (1999). Neural correlates of exposure to traumatic pictures and sound in Vietnam combat veterans with and without posttraumatic stress disorder: A positron emission tomography study. Biological Psychiatry, 45, 806–816.
Brewin, C. R., Andrews, B., & Valentine, J. D. (2000). Meta-analysis of risk factors for posttraumatic stress disorder in trauma-exposed adults. Journal of Consulting and Clinical Psychology, 68(5), 748–766.
Brinkmann, L., Buff, C., Feldker, K., Tupak, S. V., Becker, M., Herrmann, M. J., & Straube, T. (2017). Distinct phasic and sustained brain responses and connectivity of amygdala and bed nucleus of the stria terminalis during threat anticipation in panic disorder. Psychological Medicine, 47(15), 2675–2688.
Brody, A. L., Saxena, S., Schwartz, J. M., et al. (1998). FDG-PET predictors of response to behavioral therapy and pharmacotherapy in obsessive–compulsive disorder. Psychiatry Research, 84(1), 1–6.
Brunelli, S. A., & Hofer, M. A. (2007). Selective breeding for infant rat separation induced ultrasonic vocalizations: Developmental precursors of passive and active coping styles. Behavioural Brain Research, 182, 193–207.
Buff, C., Brinkmann, L., Bruchmann, M., Becker, M., Tupak, S., Herrmann, M. J., & Straube, T. (2017). Activity alterations in the bed nucleus of the stria terminalis and amygdala during threat anticipation in generalized anxiety disorder. Social Cognitive and Affective Neuroscience, 12(11), 1766–1774.
Buss, C., Meaney, M. J., Lupien, S., et al. (2007). Maternal care modulates the relationship between prenatal risk and hippocampal volume. Journal of Neuroscience, 27, 2592–2595.
Cahill, L., & McGaugh, J. L. (1998). Mechanisms of emotional arousal and lasting declarative memory. Trends in Neuroscience, 21, 273–313.
Cahill, L., Weinberger, N. M., Roozendaal, B., et al. (1999). Is the amygdala a locus of “conditioned fear”? Some questions and caveats. Neuron, 23, 227–228.
Caldji, C., Tannenbaum, B., Sharma, S., et al. (1998). Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat. Proceedings of the National Academy of Sciences of the United States of America, 95, 5335–5340.
Caldji, C., Diorio, J., & Meaney, M. J. (2003). Variations in maternal care alter GABAA receptor subunit expression in brain regions associated with fear. Neuropsychopharmacology, 28, 150–159.
Cameron, N., Parent, C., Champagne, F. A., et al. (2005). The programming of individual differences in defensive responses and reproductive strategies in the rat through variations in maternal care. Neuroscience and Biobehavioral Reviews, 29, 843–865.
Carmichael, S. T., & Price, J. L. (1995). Limbic connections of the orbital and medial prefrontal cortex in macaque monkeys. Journal of Comparative Neurology, 363(4), 615–641.
Casarotto, P. C., Girych, M., Fred, S. M., Kovaleva, V., Moliner, R., Enkavi, G., Biojone, C., Cannarozzo, C., Sahu, M. P., Kaurinkoski, K., Brunello, C. A., Steinzeig, A., Winkel, F., Patil, S., Vestring, S., Serchov, T., Diniz, C., Laukkanen, L., Cardon, I., Antila, H., … Castrén, E. (2021). Antidepressant drugs act by directly binding to TRKB neurotrophin receptors. Cell, 184(5), 1299–1313.
Caspi, A., & Roberts, B.W. (2001). personality development across the life course: The argument for change and continuity. Psychological Inquiry, 12, 49–66.
Caspi, A., Elder, G. H., & Bern, D. J. (1988). Moving away from the world: Life-course patterns of shy children. Developmental Psychology, 24, 824–831.
Caspi, A., Moffitt, T. E., Newman, D. L., & Silva, P. A. (1996). Behavioral observations at age 3 years predict adult psychiatric disorders. Longitudinal evidence from a birth cohort. Archives of General Psychiatry, 53(11), 1033–1039.
Caspi, A., Sugden, K., Moffitt, T. E., et al. (2003). Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science, 301, 386–390.
Castellano, C., Cestari, V., & Ciamei, A. (2001). NMDA receptors and learning and memory processes. Current Drug Targets, 2, 273–283.
Chamberlain, S. R., Fineberg, N. A., Menzies, L. A., Blackwell, A. D., Bullmore, E. T., Robbins, T. W., & Sahakian, B. J. (2007). Impaired cognitive flexibility and motor inhibition in unaffected first-degree relatives of patients with obsessive-compulsive disorder. The American Journal of Psychiatry, 164(2), 335–338.
Champagne, F. A., & Meaney, M. J. (2006). Stress during gestation alters postpartum maternal care and the development of the offspring in a rodent model. Biological Psychiatry, 59, 1227–1235.
Charney, D. S. (2004). Psychobiological mechanisms of resilience and vulnerability: Implications for successful adaptation to extreme stress. American Journal of Psychiatry, 161, 195–216.
Chavanne, A. V., & Robinson, O. J. (2021). The overlapping neurobiology of induced and pathological anxiety: A meta-analysis of functional neural activation. The American Journal of Psychiatry, 178(2), 156–164.
Chronis-Tuscano, A., Degnan, K. A., Pine, D. S., Perez-Edgar, K., Henderson, H. A., Diaz, Y., Raggi, V. L., & Fox, N. A. (2009). Stable early maternal report of behavioral inhibition predicts lifetime social anxiety disorder in adolescence. Journal of the American Academy of Child and Adolescent Psychiatry, 48(9), 928–935.
Clauss, J. A., & Blackford, J. U. (2012). Behavioral inhibition and risk for developing social anxiety disorder: A meta-analytic study. Journal of the American Academy of Child and Adolescent Psychiatry, 51(10), 1066–1075.
Cohen, H., & Zohar, J. (2004). An animal model of posttraumatic stress disorder: The use of cut-off behavioral criteria. Annals of the New York Academy of Sciences, 1032, 167–178.
Cohen, H., Zohar, J., Matar, M. A., et al. (2004). Setting apart the affected: The use of behavioral criteria in animal models of post traumatic stress disorder. Neuropsychopharmacology, 29, 1962–1970.
Cornwell, B. R., Johnson, L., Berardi, L., et al. (2006). Anticipation of public speaking in virtual reality reveals a relationship between trait social anxiety and startle reactivity. Biological Psychiatry, 59, 664–666.
Crestani, F., Lorez, M., Baer, K., et al. (1999). Decreased GABAA-receptor clustering results in enhanced anxiety and a bias for threat cues. Nature Neuroscience, 2(9), 833–839.
Crestani, F., Keist, R., Fritschy, J. M., et al. (2002). Trace fear conditioning involves hippocampal alpha5 GABA(A) receptors. Proceedings of the National Academy of Sciences of the United States of America, 99, 8980–8985.
Crockenberg, S. (1981). Infant irritability, mother responsiveness, and social support influences on the security of infant-mother attachment. Child Development, 52, 857–865.
Davidson, R. J., & Fox, N. A. (1989). Frontal brain asymmetry predicts infants’ response to maternal separation. Journal of Abnormal Psychology, 98, 127–131.
Davidson, R. J., Irwin, W., Anderle, M. J., et al. (2003). The neural substrates of affective processing in depressed patients treated with venlafaxine. American Journal of Psychiatry, 160(1), 64–75.
Davis, M. (1998). Are different parts of the extended amygdala involved in fear versus anxiety? Biological Psychiatry, 44, 1239–1247.
Davis, M. (2006). Neural systems involved in fear and anxiety measured with fear-potentiated startle. American Psychologist, 61, 741–756.
Davis, M., Ressler, K., Rothbaum, B. O., et al. (2006). Effects of d-cycloserine on extinction: Translation from preclinical to clinical work. Biological Psychiatry, 60, 369–375.
Davis, M., Walker, D. L., Miles, L., & Grillon, C. (2010). Phasic vs sustained fear in rats and humans: Role of the extended amygdala in fear vs anxiety. Neuropsychopharmacology, 35, 105–135.
Dawson, G., Ashman, S. B., Panagiotides, H., et al. (2003). Preschool outcomes of children of depressed mothers: Role of maternal behavior, contextual risk, and children’s brain activity. Child Development, 74, 1158–1175.
Debiec, J., & LeDoux, J. E. (2006). Noradrenergic signaling in the amygdala contributes to the reconsolidation of fear memory: Treatment implications for PTSD. Annals of the New York Academy of Sciences, 1071, 521–524.
Domschke, K., Freitag, C. M., Kuhlenbaumer, G., et al. (2004). Association of the functional V158M catechol-O-methyltransferase polymorphism in women. International Journal of Neuropsychopharmacology, 7, 183–188.
Donaldson, Z. R., Piel, D. A., Santos, T. L., et al. (2014). Developmental effects of serotonin 1A autoreceptors on anxiety and social behavior. Neuropsychopharmacology, 39(2), 291–302.
Dougherty, D. D., Rauch, S. L., Deckersbach, T., et al. (2004). Ventromedial pre-frontal cortex and amygdala dysfunction during an anger induction positron emission tomography study in patients with major depressive disorder with anger attacks. Archives of General Psychiatry, 61, 795–804.
Drevets, W. C., Price, J. L., Simpson, J. R. J., et al. (1997). Subgenual prefrontal cortex abnormalities in mood disorders. Nature, 386, 824–827.
Drew, L. J., et al. (2016). Activation of local inhibitory circuits in the dentate gyrus by adult-born neurons. Hippocampus, 26, 763–778.
Drysdale, A. T., Grosenick, L., Downar, J., Dunlop, K., Mansouri, F., Meng, Y., Fetcho, R. N., Zebley, B., Oathes, D. J., Etkin, A., Schatzberg, A. F., Sudheimer, K., Keller, J., Mayberg, H. S., Gunning, F. M., Alexopoulos, G. S., Fox, M. D., Pascual-Leone, A., Voss, H. U., Casey, B. J., … Liston, C. (2017). Resting-state connectivity biomarkers define neurophysiological subtypes of depression. Nature Medicine, 23(1), 28–38.
Dulawa, S. C., & Hen, R. (2005). Recent advances in animal models of chronic antidepressant effects: The novelty-induced hypophagia test. Neuroscience and Biobehavioral Reviews, 29, 771–783.
Erhardt, A., Akula, N., Schumacher, J., et al. (2012). Replication and meta-analysis of TMEM132D gene variants in panic disorder. Translational Psychiatry, 2, e156.
Escorihuela, R. M., Fernandez-Teruel, A., Tobena, A., et al. (1997). Labyrinth exploration, emotional reactivity, and conditioned fear in young Roman/Verh inbred rats. Behavior Genetics, 27, 573–578.
Escorihuela, R. M., Fernandez-Teruel, A., Gil, L., et al. (1999). Inbred Roman high- and low-avoidance rats: Differences in anxiety, novelty-seeking, and shuttlebox behaviors. Physiology and Behavior, 67, 19–26.
Etkin, A., & Wager, T. D. (2007). Functional neuroimaging of anxiety: A meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. The American Journal of Psychiatry, 164(10), 1476–1488.
Etkin, A., Pittenger, C., Polan, H. J., et al. (2005a). Toward a neurobiology of psychotherapy: Basic science and clinical applications. Journal of Neuropsychiatry and Clinical Neurosciences, 17, 145–158.
Etkin, A., Egner, T., Peraza, D. M., et al. (2005b). Resolving emotional conflict: A role for the rostral anterior cingulate cortex in modulating activity in the amygdala. Neuron, 51, 871–882.
Etkin, A., Buchel, C., & Gross, J. J. (2015). The neural basis of emotional regulation. Nature Reviews. Neuroscience, 16, 693–700.
Falls, W. A., Miserendino, M. J., & Davis, M. (1992). Extinction of fear-potentiated startle blockade by infusion of an NMDA antagonist into the amygdala. Journal of Neuroscience, 12, 854–863.
Fanselow, M. S., & LeDoux, J. E. (1999). Why we think plasticity underlying Pavlovian fear conditioning occurs in the basolateral amygdala. Neuron, 23, 229–232.
Farrington, D. A., Gallagher, B., Morley, L., et al. (1988). Are there any successful men from criminogenic backgrounds? Psychiatry, 51, 116–130.
Feldman, R., Greenbaum, C., & Yirmiya, N. (1999). Mother-infant affect synchrony as an antecedent of the emergence of self-control. Developmental Psychology, 35, 223–231.
Felmingham, K. L., Dobson-Stone, C., Schofield, P. R., Quirk, G. J., & Bryant, R. A. (2013). The brain-derived neurotrophic factor Val66Met polymorphism predicts response to exposure therapy in posttraumatic stress disorder. Biological Psychiatry, 73, 1059–1063.
Ferre, P., Fernandez-Teruel, A., Escorihuela, R. M., et al. (1995). Behavior of the Roman/Verh high- and low-avoidance rat lines in anxiety tests: Relationship with defecation and self-grooming. Physiology and Behavior, 58, 1209–1213.
File, S. E. (1987). The contribution of behavioural studies to the neuropharmacology of anxiety. Neuropharmacology, 26, 877–886.
Fitzgerald, J. M., DiGangi, J. A., & Phan, K. L. (2018). Functional neuroanatomy of emotion and its regulation in PTSD. Harvard Review of Psychiatry, 26(3), 116–128.
Fleming, A. S. (1988). Factors influencing maternal responsiveness in humans: Usefulness of an animal model. Psychoneuroendocrinology, 13, 189–212.
Flint J, Kendler KS (2014). The genetics of major depression. Neuron. 81(3), 484–503. https://doi.org/10.1016/j.neuron.2014.01.027. Erratum in: Neuron. 2014 Mar 5;81(5):1214. PMID: 24507187; PMCID: PMC3919201.
Fox, A. S., & Kalin, N. H. (2014). A translational neuroscience approach to understanding the development of social anxiety disorder and its pathophysiology. The American Journal of Psychiatry, 171, 1162–1173.
Fox, A. S., & Shackman, A. J. (2019). The central extended amygdala in fear and anxiety: Closing the gap between mechanistic and neuroimaging research. Neuroscience Letters, 693, 58–67.
Fox, N. A., Henderson, H. A., Rubin, K. H., et al. (2001). Continuity and discontinuity of behavioral inhibition and exuberance: Psychophysiological and behavioral influences across the first four years of life. Child Development, 72, 1–21.
Fox, N. A., Nichols, K. E., Henderson, H. A., et al. (2005). Evidence for a gene–environment interaction in predicting behavioral inhibition in middle childhood. Psychological Science, 16, 921–926.
Fox, A. S., Oler, J. A., Shackman, A. J., Shelton, S. E., Raveendran, M., McKay, D. R., et al. (2015). Intergenerational neural mediators of early-life anxious temperament. Proceedings of the National Academy of Sciences of the United States of America, 112, 9118–9122.
Frankland, P. W., Josselyn, S. A., Bradwejn, J., et al. (1997). Activation of amygdale cholecystokinin B receptors potentiates the acoustic startle response in the rat. Journal of Neuroscience, 17, 1838–1847.
Fries, E., Moragues, N., Caldji, C., et al. (2004). Preliminary evidence of altered sensitivity to benzodiazepines as a function of maternal care in the rat. Annals of the New York Academy of Sciences, 1032, 320–324.
Ganasen, K. A., Ipser, J. A., & Stein, D. J. (2010). Augmentation of cognitive behavior therapy with pharmacotherapy. Psychiatric Clinics of North America, 33, 687–699.
Gilbertson, M. W., Shenton, M. E., Ciszewski, A., et al. (2002). Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma. Nature Neuroscience, 5, 1242–1247.
Giza, A. I., et al. (2018). The BDNF Val66Met prodomain disassembles dendritic spines altering fear extinction circuitry and behavior. Neuron, 99, 163–178.
Glue, P., Wilson, S., Coupland, N., et al. (1995). The relationship between benzodiazepine receptor sensitivity and neuroticism. Journal of Anxiety Disorders, 9, 33–45.
Gorman, J. M., Kent, J. M., Sullivan, G. M., et al. (2000). Neuroanatomical hypothesis of panic disorder revised. American Journal of Psychiatry, 157(4), 493–505.
Graeff, F. G., Silveira, M. C., Nogueira, R. L., et al. (1993). Role of the amygdala and periaqueductal gray in anxiety and panic. Behavioural Brain Research, 58, 123–131.
Grant, B. F., Hasin, D. S., Blanco, C., et al. (2005). The epidemiology of social anxiety disorder in the United States: Results from the National Epidemiologic Survey on alcohol and related conditions. Journal of Clinical Psychiatry, 66(11), 1351–1361.
Gray, J. A. (1982). The neuropsychology of anxiety. Oxford University Press.
Gray, T. S., & Bingaman, E. W. (1996). The amygdala: Corticotropin-releasing factor, steroids, and stress. Critical Reviews in Neurobiology, 10, 155–168.
Gregory, A. M., et al. (2007). Juvenile mental health histories of adults with anxiety disorders. The American Journal of Psychiatry, 164, 301–308.
Grillon, C., Merikangas, K. R., Dierker, L., et al. (1999). Startle potentiation by threat of aversive stimuli and darkness in adolescents: A multi-site study. International Journal of Psychophysiology, 32, 63–73.
Gross, C., & Hen, R. (2004). The developmental origins of anxiety. Nature Reviews. Neuroscience, 5, 545–552.
Gross, C., Santarelli, L., Brunner, D., et al. (2000). Altered fear circuits in 5-HT(1A) receptor KO mice. Biological Psychiatry, 48(12), 1157–1163.
Gross, C., Zhuang, X., Stark, K., et al. (2002). Serotonin 1A receptor acts during development to establish normal anxiety-like behaviour in the adult. Nature, 416, 396–400.
Gunther, U., Benson, J., Benke, D., et al. (1995). Benzodiazepine-insensitive mice generated by targeted disruption of the gamma 2 subunit gene of gamma-aminobutyric acid type A receptors. Proceedings of the National Academy of Sciences of the United States of America, 92(17), 7749–7753.
Haapasap, J., & Tremblay, R. E. (1994). Physically aggressive boys from ages 6 to 12: Family background, parenting behavior, and prediction of delinquency. Journal of Consulting and Clinical Psychology, 62, 1044–1052.
Hamilton, S. P., Slager, S. L., Heiman, G. A., et al. (2002). Evidence for susceptibility locus for panic disorder near the catechol-O-methyltransferase gene on chromosome 22. Biological Psychiatry, 51, 591–601.
Hane, A. A., & Fox, N. A. (2006). Ordinary variations in maternal caregiving influence human infants’ stress reactivity. Psychological Science, 17, 550–556.
Hariri, A. R., Drabant, E. M., Munoz, K. E., et al. (2005). A susceptibility gene for affective disorders and the response of the human amygdala. Archives of General Psychiatry, 62, 146–152.
Hariri, A. R., Drabant, E. M., & Weinberger, D. R. (2006). Imaging genetics: Perspectives from studies of genetically driven variation in serotonin function and corticolimbic affective processing. Biological Psychiatry, 59, 888–897.
Heimberg, R. G., Dodge, C. S., Hope, D. A., et al. (1990). Cognitive–behavioral group treatment of social phobia: Comparison to a credible placebo control. Cognitive Therapy and Research, 14, 1–23.
Heisler, L. K., Chu, H. M., Brennan, T. J., et al. (1998). Elevated anxiety and antidepressant-like responses in serotonin 5-HT1A receptor mutant mice. Proceedings of the National Academy of Sciences of the United States of America, 95, 15049–15054.
Hettema, J. M., Neale, M. C., & Kendler, K. S. (2001). A review and meta-analysis of the genetic epidemiology of anxiety disorders. American Journal of Psychiatry, 158, 1568–1578.
Hettema, J. M., Prescott, C. A., Myers, J. M., et al. (2005). The structure of genetic and environmental risk factors for anxiety disorders in men and women. Archives of General Psychiatry, 62, 182–189.
Hettema, J. M., An S. S., Neale, M. C., Bukszar. J., van den Oord, E. J., Kendler, K. S., Chen, X. (2006). Association between glutamic acid decarboxylase genes and anxiety disorders, major depression, and neuroticism. Mol Psychiatry 11(8), 752–62. https://doi.org/10.1038/sj.mp.4001845. Erratum in: Mol Psychiatry. 2006 Aug;11(8):794. PMID: 16718280
Hofer, M. A. (1992). Evolutionary concepts of anxiety. In D. J. Stein & E. Hollander (Eds.), Textbook of anxiety disorders (pp. 57–70). American Psychiatric Publishing.
Irwin, W., Davidson, R. J., Lowe, M. J., et al. (1996). Human amygdala activation detected with echo-planar functional magnetic resonance imaging. Neuro Report, 7, 1765–1769.
James, W. (1884). What is an emotion? Mind, 9, 188–205.
Jimenez, J. C., Su, K., Goldberg, A. R., Luna, V. M., Biane, J. S., Ordek, G., Zhou, P., Ong, S. K., Wright, M. A., Zweifel, L., Paninski, L., Hen, R., & Kheirbek, M. A. (2018). Anxiety cells in a hippocampal-hypothalamic circuit. Neuron, 97(3), 670–683.
Jovanovic, T., Kazama, A., Bachevalier, J., et al. (2012). Impaired safety signal learning may be a biomarker of PTSD. Neuropharmacology, 62, 695–704.
Kagan, J. (2018). Galen’s prophecy: Temperament in human nature. Routledge.
Kagan, J., Reznick, J. S., & Snidman, N. (1987). The physiology and psychology of behavioral inhibition in children. Child Development, 58, 1459–1473.
Kalueff, A. V., & Tuohimaa, P. (2004). Experimental modeling of anxiety and depression. Acta Neurobiologiae Experimentalis, 64, 439–448.
Karg, K., Burmeister, M., Shedden, K., & Sen, S. (2011). The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: Evidence of genetic moderation. Archives of General Psychiatry, 68, 444–454.
Keim, S. R., & Shekhar, A. (1996). The effects of GABAA receptor blockade in the dorsomedial hypothalamic nucleus on corticotrophin (ACTH) and corticosterone secretion in male rats. Brain Research, 739, 46–51.
Keith, J., Velezmoro, R., & O’Brien, C. (2015). Correlates of cognitive flexibility in veterans seeking treatment for posttraumatic stress disorder. The Journal of Nervous and Mental Disease, 203(4), 287–293.
Kendler, K. S. (1996). Major depression and generalised anxiety disorder. Same genes, (partly) different environments – revisited. British Journal of Psychiatry, 30(Suppl), 68–75.
Kendler, K. S., Karkowski, L. M., & Prescott, C. A. (1999). Fears and phobias: Reliability and heritability. Psychological Medicine, 29, 539–553.
Kendler, K. S., Gardner, C. O., & Prescott, C. A. (2001). Panic syndromes in a population-based sample of male and female twins. Psychological Medicine, 31, 989–1000.
Kendler, K. S., Gardner, C. O., Gatz, M., et al. (2007). The sources of co-morbidity between major depression and generalized anxiety disorder in a Swedish national twin sample. Psychological Medicine, 37, 453–462.
Kenwood, M.M., Kalin, N. H. (2021). Nonhuman primate models to explore mechanisms underlying early-life temperamental anxiety. Biol Psychiatry. 89(7), 659–671. https://doi.org/10.1016/j.biopsych.2020.08.028. Epub 2020 Sep 12. PMID: 33229035; PMCID: PMC7952470.
Kerr, M., Tremblay, R. E., Pagani-Kurtz, L., & Vitaro, F. (1996). Disruptiveness, inhibition, and withdrawal as predictors of boys’ delinquency and depression. Annals of the New York Academy of Sciences, 794, 367–368.
Kessler, R. C., Berglund, P., Demler, O., et al. (2005). Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry, 62(6), 593–602.
Kim, H., Somerville, L. H., Johnstone, T., et al. (2003). Inverse amygdala and medial prefrontal cortex responses to surprised faces. Neuro Report, 14, 2317–2322.
Klein, D. F., & Fink, M. (1962). Psychiatric reaction patterns to imipramine. American Journal of Psychiatry, 119, 432–438.
Klumpp, H., Fitzgerald, J. M., Kinney, K. L., Kennedy, A. E., Shankman, S. A., Langenecker, S. A., & Phan, K. L. (2017). Predicting cognitive behavioral therapy response in social anxiety disorder with anterior cingulate cortex and amygdala during emotion regulation. NeuroImage. Clinical, 15, 25–34.
Kochanska, G. (1997). Multiple pathways to conscience for children with different temperaments: From toddlerhood to age 5. Developmental Psychology, 33, 228–240.
Konorski, J. (1967). Integrative activity of the Brain: An interdisciplinary approach. University of Chicago Press.
Korff, S., & Harvey, B. H. (2006). Animal models of obsessive–compulsive disorder: Rationale to understanding psychobiology and pharmacology. Psychiatric Clinics of North America, 29, 371–390.
Korte, S. M., & De Boer, S. F. (2003). A robust animal model of state anxiety: Fear-potentiated behaviour in the elevated plus-maze. European Journal of Pharmacology, 463, 163–175.
Last, C. G., Hansen, C., & Franco, N. (1997). Anxious children in adulthood: A prospective study of adjustment. Journal of the American Academy of Child and Adolescent Psychiatry, 36(5), 645–652.
LeDoux, J. E. (1996). The emotional brain: The mysterious underpinnings of emotional life. Simon & Schuster.
LeDoux, J. E. (2000). Emotion circuits in the brain. Annual Review of Neuroscience, 23, 155–184.
Leonardo, E. D., & Hen, R. (2006). Genetics of affective and anxiety disorders. Annual Review of Psychology, 57, 117–137.
Lesch, K. P., Bengel, D., Heilis, A., et al. (1996). Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science, 274, 1527–1531.
Levey, D. F., et al. (2021) Reproducible genetic risk loci for anxiety: Results from∼200,000 participants in the million veteran program. The American Journal of Psychiatry.
Levine, S. (1994). The ontogeny of the hypothalamic–pituitary–adrenal axis. The influence of maternal factors. Annals of the New York Academy of Sciences, 746, 275–288.
Li, A., Jing, D., Dellarco, D. V., et al. (2021). Role of BDNF in the development of an OFC-amygdala circuit regulating sociability in mouse and human. Molecular Psychiatry, 26, 955–973.
Liberzon, I., & Martis, B. (2006). Neuroimaging studies of emotional responses in PTSD. Annals of the New York Academy of Sciences, 1071, 87–109.
Liberzon, I., Taylor, S. F., Amdur, R., et al. (1999). Brain activation in PTSD in response to trauma-related stimuli. Biological Psychiatry, 45, 817–826.
Liebowitz, M. R., Schneier, F., Campeas, R., et al. (1992). Phenelzine versus atenolol in social phobia. Archives of General Psychiatry, 49, 290–300.
Lister, R. G. (1990). Ethologically-based animal models of anxiety disorders. Pharmacology and Therapeutics, 46, 321–340.
Liu, D., Diorio, J., Day, J. C., et al. (2000). Maternal care, hippocampal synaptogenesis and cognitive development in rats. Nature Neuroscience, 3, 799–806.
Lonigan, C. J., Vasey, M. W., Phillips, B. M., et al. (2004). Temperament, anxiety, and the processing of threat-relevant stimuli. Journal of Clinical Child and Adolescent Psychology, 33(1), 8–20.
Lorsch, Z. S., Loh, Y.-H. E., Purushothaman, I., Walker, D. M., Parise, E. M., Salery, M., Cahill, M. E., Hodes, G. E., Pfau, M. L., Kronman, H., Hamilton, P. J., Issler, O., Labonté, B., Ann, E., Symonds, A. E., Matthew Zucker, M., Zhang, T. Y., Meaney, M. J., Russo, S. J., Li Shen, L., Bagot, R. C., & Nestler, E. J. (2018). Estrogen receptor α drives pro-resilient transcription in mouse models of depression. Nature Communications, 9, 1116.
Low, K., Crestani, F., Keist, R., et al. (2000). Molecular and neuronal substrate for the selective attenuation of anxiety. Science, 290, 131–134.
Maier, S. F., Amat, J., Baratta, M. V., Paul, E., & Watkins, L. R. (2006). Behavioral control, the medial prefrontal cortex, and resilience. Dialogues in Clinical Neuroscience, 8(4), 397–406.
Malizia, A. L., Cunningham, V. J., Bell, C. J., et al. (1998). Decreased brain GABA(A)-benzodiazepine receptor binding in panic disorder: Preliminary results from a quantitative PET study. Archives of General Psychiatry, 55(8), 715–720.
Maren, S. (2011). Seeking a spotless mind: Extinction, deconsolidation, and erasure of fear memory. Neuron, 70, 830–845.
Maren, S., & Quirk, G. J. (2004). Neuronal signalling of fear memory. Nature Reviews. Neuroscience, 5, 844–852.
Marks, I. M., & Gelder, M. G. (1966). Different ages of onset in varieties of phobia. American Journal of Psychiatry, 123, 218–221.
Matar, M. A., Cohen, H., Kaplan, Z., et al. (2006). The effect of early poststressor intervention with sertraline on behavioral responses in an animal model of post-traumatic stress disorder. Neuropsychopharmacology, 31, 2610–2618.
Mayberg, H. S. (2007). Defining the neural circuitry of depression: Toward a new nosology with therapeutic implications. Biological Psychiatry, 61, 729–730.
Mayes, R., & Horwitz, A. V. (2005). DSM-III and the revolution in the classification of mental illness. Journal of the History of the Behavioral Sciences, 41(3), 249–267.
McCown, T. J., Vogel, R. A., & Breese, G. R. (1983). An efficient chronic conflict paradigm: Lick suppression by incremental footshock. Pharmacology, Biochemistry, and Behavior, 18, 277–279.
McDonald, A. J., (1998). Cortical pathways to the mammalian amygdala. Prog Neurobiol. 55(3), 257–332. https://doi.org/10.1016/s0301-0082(98)00003-3. PMID: 9643556.
McEwen, B. S. (1999). Stress and hippocampal plasticity. Annual Review of Neuroscience, 22, 105–122.
McEwen, B. S. (2007). Physiology and neurobiology of stress and adaptation: Central role of the brain. Physiological Reviews, 87, 873–904.
McKernan, R. M., & Whiting, P. J. (1997). Which GABAA-receptor subtypes really occur in the brain? Trends in Neuroscience, 19(4), 139–143.
Meaney, M. J. (2001). Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annual Reviews of Neuroscience, 24, 1161–1192.
Meaney, M. J., Aitken, D. H., van Berkel, C., et al. (1988). Effect of neonatal handling on age-related impairments associated with the hippocampus. Science, 239, 766–768.
Meaney, M. J., Aitken, D. H., Bhatnagar, S., et al. (1991). Postnatal handling attenuates certain neuroendocrine, anatomical, and cognitive dysfunctions associated with aging in female rats. Neurobiology of Aging, 12, 31–38.
Mehta, A. K., & Ticku, M. K. (1988). Ethanol potentiation of GABAergic transmission in cultured spinal cord neurons involves gamma-aminobutyric acid A-gated chloride channels. Journal of Pharmacology and Experimental Therapeutics, 246, 558–664.
Melo de Paula, A. J. (1977). A comparative study of lormetazepam and flurazepam in the treatment of insomnia. Clinical Therapeutics, 64, 500–508.
Mendlewicz, J., Papadimitriou, G., & Wilmotte, J. (1993). Family study of panic disorder: Comparison with generalized anxiety disorder, major depression, and normal subjects. Psychiatry Genetics, 3, 73–78.
Millan, M. J., & Brocco, M. (2003). The Vogel conflict test: Procedural aspects, gamma-aminobutyric acid, glutamate and monoamines. European Journal of Pharmacology, 463, 67–96.
Miller, M. M., & McEwen, B. S. (2006). Establishing an agenda for translational research on PTSD. Annals of the New York Academy of Sciences, 1071, 294–312.
Morgan, M. A., & LeDoux, J. E. (1995). Differential contribution of dorsal and ventral medial prefrontal cortex to the acquisition and extinction of conditioned fear in rats. Behavioral Neuroscience, 109, 681–688.
Morgan, M. A., Romanski, L. M., & LeDoux, J. E. (1993). Extinction of emotional learning contribution of medial prefrontal cortex. Neuroscience Letters, 163, 109–113.
Morilak, D. A., Barrera, G., Echevarria, D. J., et al. (2005). Role of brain norepinephrine in the behavioral response to stress. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 29, 1214–1224.
Morris, R. G., Davis, S., & Butcher, S. P. (1990). Hippocampal synaptic plasticity and NMDA receptors: A role in information storage? Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences, 329, 187–204.
Morris, J. S., Frith, C. D., Perrett, D. I., et al. (1996). A differential neural response in the human amygdala to fearful and happy facial expressions. Nature, 383, 812–815.
Munafò, M. R., Freimer, N. B., Ng, W., et al. (2009). 5-HTTLPR genotype and anxiety-related personality traits: A meta-analysis and new data. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 150B, 271–281.
Naaz F, Knight LK, Depue BE (2019) Explicit and ambiguous threat processing: Functionally dissociable roles of the amygdala and bed nucleus of the stria Terminalis. J Cogn Neurosci. 31(4), 543–559. https://doi.org/10.1162/jocn_a_01369. PMID: 30605004.
Nachmias, M., Gunnar, M., Mangelsdorf, S., et al. (1996). Behavioral inhibition and stress reactivity: The moderating role of attachment security. Child Development, 67, 508–522.
Nader, K., Schafe, G. E., & LeDoux, J. E. (2000). Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature, 406, 722–726.
Narrows, W. E., Rae, D. S., & Robins, L. N. (2002). Revised prevalence estimates of mental disorders in the United States: Using a clinical significance criterion to reconcile 2 survey’s estimates. Archives of General Psychiatry, 59, 115–123.
Nemeroff, C. B., Heim, C. M., Thase, M. E., et al. (2003). Differential responses to psychotherapy versus pharmacotherapy in patients with chronic forms of major depression and childhood trauma. Proceedings of the National Academy of Sciences of the United States of America, 100, 14293–14296.
Neria, Y. (2021). Functional neuroimaging in PTSD: From discovery of underlying mechanisms to addressing diagnostic heterogeneity. The American Journal of Psychiatry, 178(2), 128–135.
Newcomer, J. W., & Krystal, J. H. (2001). NMDA receptor regulation of memory and behavior in humans. Hippocampus, 11, 529–542.
Noyes, R., Clarkson, C., Crowe, R. R., et al. (1987). A family study of generalized anxiety disorder. American Journal of Psychiatry, 144, 1019–1024.
Oblowitz, H., & Robins, M. L. (1983). The effect of clobazam and lorazepam on the psychomotor performance of anxious patients. British Journal of Clinical Pharmacology, 16, 95–99.
Ochsner, K. N., Bunge, S. A., Gross, J. J., et al. (2002). Rethinking feelings: An FMRI study of the cognitive regulation of emotion. Journal of Cognitive Neuroscience, 14, 1215–1229.
Ohman, A., & Mineka, S. (2001). Fears, phobias, and preparedness: Toward an evolved module of fear and fear learning. Psychological Review, 108, 483–522.
Oler, J. A., Fox, A. S., Shelton, S. E., Rogers, J., Dyer, T. D., Davidson, R. J., et al. (2010). Amygdalar and hippocampal substrates of anxious temper-ament differ in their heritability. Nature, 466, 864–868.
Otowa, T., Hek, K., Lee, M., Byrne, E. M., Mirza, S. S., Nivard, M. G., et al. (2016). Meta-analysis of genome-wide association studies of anxiety disorders. Molecular Psychiatry, 21, 1391–1399.
Padilla-Coreano, N., Bolkan, S. S., Pierce, G. M., Blackman, D. R., Hardin, W. D., Garcia-Garcia, A. L., Spellman, T. J., & Gordon, J. A. (2016). Direct ventral hippocampal-prefrontal input is required for anxiety-related neural activity and behavior. Neuron, 89(4), 857–866.
Paterson, A., Whiting, P. J., Gray, J. A., et al. (2001). Lack of consistent behavioural effects of Maudsley reactive and non-reactive rats in a number of animal tests of anxiety and activity. Psychopharmacology (Berlin), 154, 336–342.
Pavlov, I. P. (1927). Conditioned reflexes. Oxford University Press.
Pérez-Edgar, K., Fox, N. A. (2005). Temperament and anxiety disorders. Child Adolesc Psychiatr Clin N Am. 14(4), 681–706, viii. https://doi.org/10.1016/j.chc.2005.05.008. PMID: 16171698.
Phan, K. L., Taylor, S. F., Welsh, R. C., et al. (2004). Neural correlates of individual ratings of emotional salience: A trial-related fMRI study. NeuroImage, 21(2), 768–780.
Phan, K. L., Fitzgerald, D. A., Nathan, P. J., et al. (2005). Neural substrates for voluntary suppression of negative affect: A functional magnetic resonance imaging study. Biological Psychiatry, 57, 210–219.
Phelps, E. A. (2004). Human emotion and memory: Interactions of the amygdala and hippocampal complex. Current Opinion in Neurobiology, 14, 198–202.
Phelps, E. A., & LeDoux, J. E. (2005). Contributions of the amygdala to emotion processing: From animal models to human behavior. Neuron, 48, 175–187.
Phelps, E. A., O’Connor, K. J., Gatenby, J. C., et al. (2001). Activation of the left amygdala to a cognitive representation of fear. Nature Neuroscience, 4, 437–441.
Phelps, E. A., Delgado, M. R., Nearing, K. I., et al. (2004). Extinction learning in humans: Role of the amygdala and umPFC. Neuron, 43, 897–905.
Phillips, M. L., Young, A. W., Senior, C., et al. (1997). A specific neural substrate for perceiving facial expressions of disgust. Nature, 389, 495–498.
Pisula, W., & Osinski, J. T. (2000). A comparative study of the behavioral patterns of RLA/Verh and RHA/Verh rats in the exploration box. Behavior Genetics, 30, 375–384.
Pitkanen, A., Savander, V., & LeDoux, J. E. (1997). Organization of intra-amygdaloid circuitries in the rat: An emerging framework for understanding functions of the amygdala. Trends in Neuroscience, 20, 517–523.
Pitman, R. K., & Delahanty, D. L. (2005). Conceptually driven pharmacologic approaches to acute trauma. CNS Spectrum, 10, 99–106.
Prior, M., Smart, D., Sanson, A., et al. (2000). Does shy-inhibited temperament in childhood lead to anxiety problems in adolescence? Journal of the American Academy of Child and Adolescent Psychiatry, 39(4), 461–468.
Protopopescu, X., Pan, H., Tuescher, O., et al. (2005). Differential time courses and specificity of amygdala activity in posttraumatic stress disorder subjects and normal control subjects. Biological Psychiatry, 57, 464–473.
Pruessner, J. C., Champagne, F., Meaney, M. J., et al. (2004). Dopamine release in response to a psychological stress in humans and its relationship to early maternal care: A positron emission tomography study using [C]raclopride. Journal of Neuroscience, 24, 2825–2831.
Purves, K. L., et al. (2020). A major role for common genetic variation in anxiety disorders. Molecular Psychiatry, 25, 3292–3303.
Quintero, S., Mellanby, J., Thompson, M. R., et al. (1985). Septal driving of hippocampal theta rhythm: Role of gamma-aminobutyrate-benzodiazepine receptor complex in mediating effects of anxiolytics. Neuroscience, 16, 875–884.
Quirk, G. J., & Beer, J. S. (2006). Prefrontal involvement in the regulation of emotion: Convergence of rat and human studies. Current Opinion in Neurobiology, 16, 723–727.
Quirk, G. J., Russo, G. K., Barron, J. L., et al. (2000). The role of ventromedial prefrontal cortex in the recovery of extinguished fear. Journal of Neuroscience, 20, 6225–6231.
Quirk, G. J., Likhtik, E., Pelletier, J. G., et al. (2003). Stimulation of medial prefrontal cortex decreases the responsiveness of central amygdala output neurons. Journal of Neuroscience, 23, 8800–8807.
Quirk, G. J., Gonzalez-Lima, F., & Garcia, R. (2006). Prefrontal mechanisms in extinction of conditioned fear. Biological Psychiatry, 59, 337–343.
Ramage, A. E., Laird, A. R., Eickhoff, S. B., Acheson, A., Peterson, A. L., Williamson, D. E., Telch, M. J., & Fox, P. T. (2013). A coordinate-based meta-analytic model of trauma processing in posttraumatic stress disorder. Human Brain Mapping, 34(12), 3392–3399.
Rau, V., DeCola, J. P., & Fanselow, M. S. (2005). Stress-induced enhancement of fear learning: An animal model of posttraumatic stress disorder. Neuroscience and Biobehavioral Reviews, 29, 1207–1223.
Rauch, S. L., Van Der Kolk, B. A., Fisler, R. E., et al. (1996). A symptom provocation study of posttraumatic stress disorder using positron emission tomography and script-driven imagery. Archives of General Psychiatry, 53, 380–387.
Rescorla, R. A., & Heth, C. D. (1975). Reinstatement of fear to an extinguished conditioned stimulus. Journal of Experimental Psychology: Animal Behavior Processes, 1, 88–96.
Richardson-Jones, J. W., Craige, C. P., Nguyen, T. H., et al. (2011). Serotonin-1A autoreceptors are necessary and sufficient for the normal formation of circuits underlying innate anxiety. Journal of Neuroscience, 31, 6008–6018.
Richter-Levin, G. (1998). Acute and long-term behavioral correlates of underwater trauma–potential relevance to stress and post-stress syndromes. Psychiatry Research, 79, 73–83.
Rifkin-Graboi, A., Meaney, M. J., Chen, H., Bai, J., Hameed, W. B., Tint, M. T., Broekman, B. F. P., Chong, Y. S., Gluckman, P. D., Fortier, M. V., & Qiu, A. (2015). Antenatal maternal anxiety predicts variations in neural structures implicated in anxiety disorders in newborn. Journal of the American Academy of Child & Adolescent Psychiatry, 54, 313–321.
Rittenhouse, P. A., Bakkum, E. A., O’Connor, P. A., et al. (1992). Comparison of neuroendocrine and behavioral effects of ipsapirone, a 5-HT1A agonist, in three stress paradigms: Immobilization, forced swim and conditioned fear. Brain Research, 580, 205–214.
Roceri, M., Hendriks, W., Racagni, G., et al. (2002). Early maternal deprivation reduces the expression of BDNF and NMDA receptor subunits in rat hippocampus. Molecular Psychiatry, 7(6), 609–616.
Rodrigues, S. M., Schafe, G. E., & LeDoux, J. E. (2004). Molecular mechanisms underlying emotional learning and memory in the lateral amygdala. Neuron, 44, 75–91.
Roffman, J. L., Marci, C. D., Glick, D. M., et al. (2005). Neuroimaging and the functional neuroanatomy of psychotherapy. Psychological Medicine, 35, 1385–1398.
Rogan, M. T., Leon, K. S., Perez, D. L., et al. (2005). Distinct neural signatures for safety and danger in the amygdala and striatum of the mouse. Neuron, 46, 309–320.
Rosa-Alcázar, Á., Olivares-Olivares, P. J., Martínez-Esparza, I. C., Parada-Navas, J. L., Rosa-Alcázar, A. I., & Olivares-Rodríguez, J. (2020). Cognitive flexibility and response inhibition in patients with obsessive-compulsive disorder and generalized anxiety disorder. International Journal of Clinical and Health Psychology: IJCHP, 20(1), 20–28.
Rose, R. J., & Ditto, W. B. (1983). A developmental-genetic analysis of common fears from early adolescence to early adulthood. Child Development, 54, 361–368.
Rosen, J. B., & Schulkin, J. (1998). From normal fear to pathological anxiety. Psychological Review, 105, 325–350.
Rosen, J. B., Hamerman, E., Sitcoske, M., et al. (1996). Hyperexcitability: Exaggerated fear-potentiated startle produced by partial amygdala kindling. Behavioral Neuroscience, 110, 43–50.
Rosenbaum, J. F., Biederman, J., Hirshfeld, D. R., et al. (1991). Further evidence of an association between behavioral inhibition and anxiety disorders: Results from a family study of children from a non-clinical sample. Journal of Psychiatric Research, 25(1–2), 49–65.
Rosenkranz, J. A., Moore, H., & Grace, A. A. (2003). The prefrontal cortex regulates lateral amygdala neuronal plasticity and responses to previously conditioned stimuli. Journal of Neuroscience, 23, 11054–11064.
Roth, W. T. (2005). Physiological markers for anxiety: Panic disorder and phobias. International Journal of Psychophysiology, 58, 190–198.
Rothbart, M. K. (2004). Differentiated measures of temperament and multiple pathways to childhood disorders. Journal of Clinical Child and Adolescent Psychology, 33, 82–87.
Rothe, C., Koszycki, D., Bradwein, J., et al. (2006). Association of the Val-158Met catechol O-methyl transferase genetic polymorphism with panic disorder. Neuropsychopharmacology, 31, 2237–2242.
Roy-Byrne, P., Cowley, D. S., Greenblatt, D. J., et al. (1990). Reduced benzodiazepine sensitivity in panic disorder. Archives of General Psychiatry, 47, 534–538.
Roy-Byrne, P., Wingerson, D. K., Radant, A., et al. (1996). Reduced benzodiazepine sensitivity in patients with panic disorder: Comparison with patients with obsessive–compulsive disorder and normal subjects. American Journal of Psychiatry, 153, 1444–1449.
Rubin, K. H., Burgess, K. B., & Hastings, P. D. (2002). Stability and social-behavioral consequences of toddlers’ inhibited temperament and parenting behaviors. Child Development, 73, 483–495.
Russo, S. J., Murrough, J. W., Han, M. H., et al. (2012). Neurobiology of resilience. Nature Neuroscience, 15, 1475–1484.
Sajdyk, T. J., & Shekhar, A. (1997). Excitatory amino acid receptor antagonists block the cardiovascular and anxiety responses elicited by gamma-aminobutyric acid A receptor blockade in the basolateral amygdala of rats. Journal of Pharmacology and Experimental Therapeutics, 283, 969–977.
Sajdyk, T. J., & Shekhar, A. (2000). Sodium lactate elicits anxiety in rats after repeated GABA receptor blockade in the basolateral amygdala. European Journal of Pharmacology, 394, 265–273.
Sajdyk, T. J., Schober, D. A., Gehlert, D. R., et al. (1999). Role of corticotropin-releasing factor and urocortin within the basolateral amygdala of rats in anxiety and panic responses. Behavioural Brain Research, 100, 207–215.
Sanders, S. K., & Shekhar, A. (1995). Regulation of anxiety by GABAA receptors in the rat amygdala. Pharmacology, Biochemistry and Behavior, 52, 701–706.
Sanders, S. K., Morzorati, S. L., & Shekhar, A. (1995). Priming of experimental anxiety by repeated subthreshold GABA blockade in the rat amygdala. Brain Research, 699, 250–259.
Santarelli, L., Saxe, M., Gross, C., Surget, A., Battaglia, F., Dulawa, S., Weisstaub, N., Lee, J., Duman, R., Arancio, O., Belzung, C., & Hen, R. (2003). Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science (New York, NY), 301(5634), 805–809.
Schaefer, S. M., Jackson, D. C., Davidson, R. J., et al. (2002). Modulation of amygdalar activity by the conscious regulation of negative emotion. Journal of Cognitive Neuroscience, 14, 913–921.
Schanberg, S. M., Evoniuk, G., & Kuhn, C. M. (1984). Tactile and nutritional aspects of maternal care: Specific regulators of neuroendocrine function and cellular development. Proceedings of the Society for Experimental Biology and Medicine, 175, 135–146.
Scherrer, J. F., True, W. R., Xian, H., et al. (2000). Evidence for genetic influences common and specific to symptoms of generalized anxiety and panic. Journal of Affective Disorders, 57, 25–35.
Schwartz, C. E., Wright, C. I., Shin, L. M., et al. (2003). Inhibited and uninhibited infants “grown up”: Adult amygdalar response to novelty. Science, 300, 1952–1953.
Servatius, R. J., Ottenweller, J. E., & Natelson, B. H. (1995). Delayed startle sensitization distinguishes rats exposed to one or three stress sessions: Further evidence toward an animal model of PTSD. Biological Psychiatry, 38, 539–546.
Shackman, A. J., Fox, A. S., Oler, J. A., Shelton, S. E., Davidson, R. J., & Kalin, N. H. (2013). Neural mechanisms underlying heterogeneity in the presentation of anxious temperament. Proceedings of the National Academy of Sciences of the United States of America, 110, 6145–6150.
Shackman, A. J., Fox A. S. (2016) Contributions of the Central Extended Amygdala to Fear and Anxiety. J Neurosci. 36(31), 8050–63. https://doi.org/10.1523/JNEUROSCI.0982-16.2016. PMID: 27488625; PMCID: PMC4971357
Shekhar, A., Keim, S. R., Simon, J. R., et al. (1996). Dorsomedial hypothalamic GABA dysfunction produces physiological arousal following sodium lactate infusions. Pharmacology, Biochemistry, and Behavior, 55, 249–256.
Shekhar, A., Sajdyk, T. S., Keim, S. R., et al. (1999). Role of the basolateral amygdala in panic disorder. Annals of the New York Academy of Sciences, 877, 747–750.
Shekhar, A., Sajdyk, T. J., Gehlert, D. R., et al. (2003). The amygdala, panic disorder, and cardiovascular responses. Annals of the New York Academy of Sciences, 985, 308–325.
Shin, L. M., Orr, S. P., Carson, M. A., et al. (2004). Regional cerebral blood flow in the amygdala and medial prefrontal cortex during traumatic imagery in male and female Vietnam veterans with PTSD. Archives of General Psychiatry, 61, 168–176.
Shin, L. M., Wright, C. I., Cannistraro, P. A., et al. (2005). A functional magnetic resonance imaging study of amygdala and medial prefrontal cortex responses to overtly presented fearful faces in posttraumatic stress disorder. Archives of General Psychiatry, 62, 273–281.
Shumyatsky, G. P., Malleret, G., Shin, R. M., et al. (2005). Stathmin, a gene enriched in the amygdala, controls both learned and innate fear. Cell, 123(4), 697–709.
Sibille, E., & Hen, R. (2001). Combining genetic and genomic approaches to study mood disorders. European Neuropsychopharmacology, 11, 413–421.
Siever, L. J., Torgersen, S., Gunderson, J. G., et al. (2002). The borderline diagnosis III: Identifying endophenotypes for genetic studies. Biological Psychiatry, 51, 964–968.
Skre, I., Onstad, S., Torgersen, S., et al. (1993). A twin study of DSM-III-R anxiety disorders. Acta Psychiatrica Scandinavica, 88, 85–92.
Smith, G. W., Aubry, J. M., Dellu, F., et al. (1998). Corticotropin releasing factor receptor 1-deficient mice display decreased anxiety, impaired stress response, and aberrant neuroendocrine development. Neuron, 20, 1093–1102.
Smoller, J. W. (2016). The genetics of stress-related disorders: PTSD, depression, and anxiety disorders. Neuropsychopharmacology, 41, 297–319.
Smoller, J. W., Rosenbaum, J. F., Biederman, J., et al. (2003). Association of a genetic marker at the corticotropin-releasing hormone locus with behavioral inhibition. Biological Psychiatry, 54, 1376–1381.
Soe, N. N., Wen, D. J., Poh, J. S., Chong, Y. S., Broekman, B. F., Chen, H., Shek, L. P., Tan, K. H., Gluckman, P. D., Fortier, M. V., Meaney, M. J., & Qiu, A. (2017). Perinatal maternal depressive symptoms alter amygdala functional connectivity in girls. Human Brain Mapping, 39, 680–690.
Soliman, F., Glatt, C. E., Bath, K. G., Levita, L., Jones, R. M., Pattwell, S. S., Jing, D., Tottenham, N., Amso, D., Somerville, L. H., et al. (2010). A genetic variant BDNF polymorphism alters extinction learning in both mouse and human. Science, 327, 863–866.
Sotres-Bayon, F., Bush, D. E., & LeDoux, J. E. (2004). Emotional perseveration: An update on prefrontal-amygdala interactions in fear extinction. Learning and Memory, 11, 525–535.
Spielberger, C. D. (1971). Trait-state anxiety and motor behavior. Journal of Motor Behavior, 3, 265–279.
Steimer, T., & Driscoll, P. (2003). Divergent stress responses and coping styles in psychogenetically selected Roman high-(RHA) and low-(RLA) avoidance rats: Behavioural, neuroendocrine and developmental aspects. Stress, 6, 87–100.
Stein, M. B., Goldin, P. R., Sareen, J., et al. (2002). Increased amygdala activation to angry and contemptuous faces in generalized social phobia. Archives of General Psychiatry, 59, 1027–1034.
Stein, M. B., Seedat, S., & Gelernter, J. (2006). Serotonin transporter gene promoter polymorphism predicts SSRI response in generalized social anxiety disorder. Psychopharmacology, 187, 68–72.
Stein, M. B. (2009). Neurobiology of generalized anxiety disorder. J Clin Psychiatry, 70 Suppl 2:15–9. https://doi.org/10.4088/jcp.s.7002.03. PMID: 19371502
Straube, T., Mentzel, H. J., & Miltner, W. H. (2005). Common and distinct brain activation to threat and safety signals in social phobia. Neuropsychobiology, 52, 163–168.
Stutzmann, G. E., & LeDoux, J. E. (1999). GABAergic antagonists block the inhibitory effects of serotonin in the lateral amygdala: A mechanism for modulation of sensory inputs related to fear conditioning. Journal of Neuroscience, 19(11), RC8.
Sullivan, G. M., Apergis, J., Gorman, J. M., et al. (2003). Rodent doxapram model of panic: Behavioral effects and c-Fos immunoreactivity in the amygdala. Biological Psychiatry, 53, 863–870.
Suomi, S. J. (1997). Early determinants of behaviour: Evidence from primate studies. British Medical Bulletin, 53, 170–184.
Tang, A., Van Lieshout, R. J., Lahat, A., Duku, E., Boyle, M. H., Saigal, S., & Schmidt, L. A. (2017). Shyness trajectories across the first four decades predict mental health outcomes. Journal of Abnormal Child Psychology, 45(8), 1621–1633.
Tang, A., Crawford, H., Morales, S., Degnan, K. A., Pine, D. S., & Fox, N. A. (2020). Infant behavioral inhibition predicts personality and social outcomes three decades later. Proceedings of the National Academy of Sciences of the United States of America, 117(18), 9800–9807.
Tanis, K. Q., Newton, S. S., & Duman, R. S. (2007). Targeting neurotrophic/growth factor expression and signaling for antidepressant drug development. CNS and Neurological Disorders Drug Targets, 6, 151–160.
Tecott, L. H. (2000). Designer genes and anti-anxiety drugs. Nature Neuroscience, 3, 529–530.
Tecott, L. H., Logue, S. F., Wehner, J. M., et al. (1998). Perturbed dentate gyrus function in serotonin 5-HT2C receptor mutant mice. Proceedings of the National Academy of Sciences of the United States of America, 95, 15026–15031.
Thomas, A., & Chess, S. (1977). Temperament and development. Brunner/Mazel.
Toren, P., et al. (2000). Neurocognitive correlates of anxiety disorders in children: A preliminary report. Journal of Anxiety Disorders, 14, 239–247.
Torgersen, S. (1979). The nature and origin of common phobic fears. British Journal of Psychiatry, 134, 343–351.
Torgersen, S., Lygren, S., Oien, P. A., et al. (2000). A twin study of personality disorders. Comparative Psychiatry, 41, 416–425.
Tronel, S., & Alberini, C. M. (2007). Persistent disruption of a traumatic memory by postretrieval inactivation of glucocorticoid receptors in the amygdala. Biological Psychiatry, 62(1), 33–39.
Urry, H. L., van Reekum, C. M., Johnstone, T., et al. (2003). Neural correlates of voluntarily regulating negative affect. Program no. 725.18. Abstract Viewer/Itinerary Planner. Society for NeuroScience online, Washington, DC.
Van Bockstaele, E. J., Colago, E. E., & Valentino, R. J. (1998). Amygdaloid corticotropin-releasing factor targets locus coeruleus dendrites: Substrate for the co-ordination of emotional and cognitive limbs of the stress response. Journal of Neuroendocrinology, 10(10), 743–757.
Wakizono, T., Sawamura, T., Shimizu, K., et al. (2007). Stress vulnerabilities in an animal model of post-traumatic stress disorder. Physiology and Behavior, 90(4), 687–695.
Walker, C. D., Rivest, R. W., Meaney, M. J., et al. (1989). Differential activation of the pituitary-adrenocortical axis after stress in the rat: Use of two genetically selected lines (Roman low- and high-avoidance rats) as a model. Journal of Endocrinology, 123, 477–485.
Waszczuk, M. A., et al. (2014). The phenotypic and genetic structure of depression and anxiety disorder symptoms in childhood, adolescence, and young adulthood. JAMA Psychiatry, 71(8), 905–916.
Weaver, I. C. G., Cervoni, N., D’Alessio, A. C., et al. (2004). Epigenetic programming through maternal behavior. Nature Neuroscience, 7, 847–854.
Weaver, I. C. G., Champagne, F. A., Brown, S. E., et al. (2005). Reversal of maternal programming of stress responses in adult offspring through methyl supplementation: Altering epigenetic marking later in life. Journal of Neuroscience, 25, 11045–11054.
Weaver, I. C. G., D’Alessio, A. C., Brown, S. E., et al. (2007). The transcription factor NGFI-A mediates epigenetic programming: Altering epigenetic marking through immediate early genes. Journal of Neuroscience, 27, 1756–1768.
Wee, C. Y., Tuan, T. A., Broekman, B. F., Ong, M. Y., Chong, Y. S., Kwek, K., Shek, L. P., Saw, S. M., Gluckman, P. D., Fortier, M. V., Meaney, M. J., & Qiu, A. (2016). Neonatal neural networks predict children behavioral profiles in later life. Human Brain Mapping, 38, 1362–1373.
Wehner, J. M., Radcliffe, R. A., Rosmann, S. T., et al. (1997). Quantitative trait locus analysis of contextual fear conditioning in mice. Nature Genetics, 17, 331–334.
Weinberg, J., & Levine, S. (1977). Early handling influences on behavioral and physiological responses during active avoidance. Developmental Psychobiology, 10, 161–169.
Woo, J. M., Yoon, K. S., & Yu, B. H. (2002). Catechol-O-methyltransferase genetic polymorphism in panic disorder. American Journal of Psychiatry, 159, 1785–1787.
Zhang, T.-Y., Bagot, R., Parent, C., et al. (2006). Maternal programming of defensive responses through sustained effects on gene expression. Biological Psychiatry, 73, 72–89.
Zhang, L., Benedek, D. M., Fullerton, C. S., Forsten, R. D., Naifeh, J. A., Li, X. X., Hu, X. Z., Li, H., Jia, M., Xing, G. Q., et al. (2014). PTSD risk is associated with BDNF Val66Met and BDNF overexpression Mol. Psychiatry, 19, 8–10.
Zilverstand, A., Parvaz, M. A., & Goldstein, R. Z. (2017). Neuroimaging cognitive reappraisal in clinical populations to define neural targets for enhancing emotion regulation. A systematic review. NeuroImage, 151, 105–116.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Section Editor information
Rights and permissions
Copyright information
© 2023 Springer Nature Switzerland AG
About this entry
Cite this entry
Meaney, M.J., Liebowitz, M.R., David Leonardo, E. (2023). Neurobiology of Anxiety Disorders. In: Tasman, A., et al. Tasman’s Psychiatry. Springer, Cham. https://doi.org/10.1007/978-3-030-42825-9_84-1
Download citation
DOI: https://doi.org/10.1007/978-3-030-42825-9_84-1
Received:
Accepted:
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-42825-9
Online ISBN: 978-3-030-42825-9
eBook Packages: Springer Reference MedicineReference Module Medicine