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Cognitive Enhancers in Exposure Therapy for Anxiety and Related Disorders

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Exposure Therapy

Abstract

Although exposure-based therapies have demonstrated effectiveness in the treatment of anxiety and related disorders, there remain a significant number of individuals who do not respond or only show partial response even after an adequate course of the treatment. Recent research suggests that augmentation agents can enhance the core learning processes of exposure-based therapy, thus potentially improving treatment response and maintenance of gains in the long-term. This chapter provides an overview of the current state of cognitive enhancers for the treatment of psychological disorders, particularly in the realm of anxiety.

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References

  • Abercrombie, H. C., Speck, N. S., & Monticelli, R. M. (2006). Endogenous cortisol elevations are related to memory facilitation only in individuals who are emotionally aroused. Psychoneuroendocrinology, 31, 187–196.

    Article  PubMed  Google Scholar 

  • Airaksinen, E., Larsson, M., & Forsell, Y. (2005). Neuropsychologcial functions in anxiety disorders in population-based samples; Evidence of episodic memory dysfunction. Journal of Psychiatric Research, 39, 207–214.

    Article  PubMed  Google Scholar 

  • Aouizerate, B., Martin-Guehl, C., & Tignol, J. (2004). Neurobiology and pharmacotherapy of social phobia. Encephale, 30, 301–313.

    Article  PubMed  Google Scholar 

  • Arenos, J. D., Musty, R. E., & Bucci, D. J. (2006). Blockade of cannabinoid CB1 receptors alters contextual learning and memory. European Journal of Pharmacology, 539, 177–183.

    Article  PubMed  Google Scholar 

  • Arnsten, A. F. (2004). Adrenergic targets for the treatment of cognitive deficits in schizophrenia. Psychopharmacology, 174, 25–31.

    Article  PubMed  Google Scholar 

  • Arnsten, A. F., & Goldman-Rakic, P. S. (1985). Alpha 2-adrenergic mechanisms in prefrontal cortex associated with cognitive decline in aged nonhuman primates. Science, 230, 1273–1276.

    Article  PubMed  Google Scholar 

  • Asmundson, G. J., Stein, M. B., Larsen, D. K., & Walker, J. R. (1994). Neurocognitive function in panic disorder and social phobia patients. Anxiety, 1, 201–207.

    PubMed  Google Scholar 

  • Baldwin, D. S., Anderson, I. M., Nutt, D. J., Bandelow, B., Bon, A., Davidson, J. R., et al. (2005). British Association for Psychopharmacology: Evidence-based guidelines for the pharmacological treatment of anxiety disorders: Recommendations from the British Association for Psychopharmacology. Journal of Psychopharmacology, 19, 567–596.

    Article  PubMed  Google Scholar 

  • Barlow, D. H., Gorman, J. M., Shear, M. K., & Woods, S. W. (2000). Cognitive-behavioral therapy, imipramine or their combination for panic disorder: A randomized controlled trial. Journal of the American Medical Association, 283, 2529–2536.

    Article  PubMed  Google Scholar 

  • Barreto, R. E., Volpato, G. L., & Pottinger, T. G. (2006). The effect of elevated blood cortisol levels on the extinction of a conditioned stress response in rainbow trout. Hormones and Behavior, 50, 484–488.

    Article  PubMed  Google Scholar 

  • Barrett, D., Shumake, J., Jones, D., & Gonzalez-Lima, F. (2003). Metabolic mapping of mouse brain activity after extinction of a conditioned emotional response. Journal of Neuroscience, 23, 5740–5749.

    PubMed  Google Scholar 

  • Beckner, V. E., Tucker, D. M., Delville, Y., & Mohr, D. C. (2006). Stress facilitates consolidation of verbal memory for a film but does not affect retrieval. Behavioral Neuroscience, 120, 518–527.

    Article  PubMed  Google Scholar 

  • Berchtold, N. C., Castello, N., & Cotman, C. W. (2010). Exercise and time-dependent benefits to learning and memory. Neuroscience, 167, 588–597.

    Article  PubMed  Google Scholar 

  • Boulenger, J. P., Uhde, T. W., Wolff, E. A., IIIrd, & Post, R. M. (1984). Increased sensitivity to caffeine in patients with panic disorders: Preliminary evidence. Archives of General Psychiatry, 41, 1067–1071.

    Article  PubMed  Google Scholar 

  • Bouton, M. E., Vurbic, D., & Woods, A. M. (2008). d-cycloserine facilitates context-specific fear extinction learning. Neurobiology of Learning & Memory, 90, 504–510.

    Article  Google Scholar 

  • Breslau, N., & Klein, D. F. (1999). Smoking and panic attacks: An epidemiologic investigation. Archives of General Psychiatry, 56, 1141–1147.

    Article  PubMed  Google Scholar 

  • Brioni, J. D., O’Neill, A. B., Kim, D. J., & Decker, M. W. (1993). Nicotinic receptor agonists exhibit anxiolytic like effects on the elevated plus-maze test. European Journal of Pharmacology, 238, 1–8.

    Article  PubMed  Google Scholar 

  • Buchanan, T. W., & Lovallo, W. R. (2001). Enhanced memory for emotional material following stress-level cortisol treatment in humans. Psychoneuroendocrinology, 26, 307–317.

    Article  PubMed  Google Scholar 

  • Bueller, J. A., Aftab, M., Sen, S., Gomez-Hassan, D., Burmeister, M., & Zubieta, J. K. (2006). BDNF Val66Met allele is associated with reduced hippocampal volume in healthy subjects. Biological Psychiatry, 599, 812–815.

    Article  Google Scholar 

  • Cahill, L., Gorski, L., & Le, K. (2003). Enhanced human memory consolidation with post-learning stress: Interaction with the degree of arousal at encoding. Learning & Memory, 10, 270–274.

    Article  Google Scholar 

  • Cai, W. H., Blundell, J., Han, J., Greene, R. W., & Powell, C. M. (2006). Postreactivation glucocorticoids impair recall of established fear memory. Journal of Neuroscience, 26, 9560–9566.

    Article  PubMed  Google Scholar 

  • Cain, C. K., Blouin, A. M., & Barad, M. (2004). Adrenergic transmission facilitates extinction of conditional fear in mice. Learning & Memory, 11, 1791–87.

    Article  Google Scholar 

  • Cape, J., Whittington, C., Buszewicz, M., Wallace, P., & Underwood, L. (2010). Brief psychological therapies for anxiety and depression in primary care: Meta-analysis and meta-regression. BMC Medical Ethics, 25, 38.

    Google Scholar 

  • Charney, D. S., Heninger, G. R., & Breier, A. (1984). Noradrenergic function in panic anxiety. Effects of yohimbine in healthy subjects and patients with agoraphobia and panic disorder. Archives of General Psychiatry, 41, 751–763.

    Google Scholar 

  • Charney, D. S., Heninger, G. R., & Jatlow, P. I. (1985). Increased anxiogenic effects of caffeine in panic disorders. Archives of General Psychiatry, 42, 233–243.

    Article  PubMed  Google Scholar 

  • Charney, D. S., & Manji, H. K. (2004). Life stress, genes, and depression: Multiple pathways lead to increased risk and new opportunities for intervention. Science’s STKE Signal Transduction Knowledge Environment, 2004(225), r5.

    Google Scholar 

  • Charney, D. S., Woods, S. W., Goodman, W. K., & Heninger, G. R. (1987). Neurobiological mechanisms of panic anxiety: Biochemical and behavioral correlates of yohimbine-induced panic attacks. American Journal of Psychiatry, 144, 1030–1036.

    PubMed  Google Scholar 

  • Chen, Y., & Parrish, T. B. (2009). Caffeine dose effect on activation-induced BOLD and CBF responses. Neuroimage, 46, 577–583.

    Article  PubMed  Google Scholar 

  • Chhatwal, J. P., Davis, M., Maguschak, K. A., & Ressler, K. J. (2005). Enhancing cannabinoid neurotransmission augments the extinction of conditioned fear. Neuropsychopharmacology, 30, 516–524.

    Article  PubMed  Google Scholar 

  • Chhatwal, J. P., Gutman, A. R., Maguschak, K. A., Bowser, M. E., Yang, Y., Davis, M., et al. (2009). Functional interactions between endocannabinoid and CCK neurotransmitter systems may be critical for extinction learning. Neuropsychopharmacology, 34, 509–521.

    Article  PubMed  Google Scholar 

  • Cosci, F., Abrams, K., Schruers, K. R., Rickelt, J., & Griez, E. J. (2006). Effect of nicotine on 35% CO2-induced anxiety: A study in healthy volunteers. Nicotine & Tobacco Research, 8, 511–517.

    Article  Google Scholar 

  • Cotman, C. W., & Berchtold, N. C. (2002). Exercise: A behavioral intervention to enhance brain health and plasticity. Trends in Neuroscience, 25, 295–301.

    Article  Google Scholar 

  • Curtis, G. C., Abelson, J. L., & Gold, P. W. (1997). Adrenocorticotropic hormone and cortisol responses to corticotropin-releasing hormone: Changes in panic disorder and effects of alprazolam treatment. Biological Psychiatry, 41, 76–85.

    Article  PubMed  Google Scholar 

  • Davis, M., Barad, M., Otto, M. W., & Southwick, S. (2006). Combining pharmacotherapy with cognitive behavior therapy: Traditional and new approaches. Journal of Traumatic Stress, 19, 571–581.

    Article  PubMed  Google Scholar 

  • Davis, M., Ressler, K., Rothbaum, B. O., & Richardson, R. (2006). Effects of d-cycloserine on extinction: Translation from preclinical to clinical work. Biological Psychiatry, 60, 369–375.

    Article  PubMed  Google Scholar 

  • de la Mora, M. P., Gallegos-Cari, A., Arizmendi-García, Y., Marcellino, D., & Fuxe, K. (2010). Role of dopamine receptor mechanisms in the amygdaloid modulation of fear and anxiety: Structural and functional analysis. Progress in Neurobiology, 90, 198–216.

    Article  PubMed  Google Scholar 

  • DeMet, E., Stein, M. K., Tran, C., Chicz-DeMet, A., Sangdahl, C., & Nelsons, J. (1989). Caffeine taste test for panic disorder: Adenosine receptor supersensitivity. Psychiatric Research, 30, 231–242.

    Article  Google Scholar 

  • Durstewitz, D., & Seamans, J. K. (2002). The computational role of dopamine D1 receptors in working memory. Neural Network, 15, 561–572.

    Article  Google Scholar 

  • Egan, M. F., Kojima, M., Callicott, J. H., Goldberg, T. E., Kolachana, B. S., Bertolino, A., et al. (2003). The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell, 112, 257–269.

    Article  PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Fiedorowicz, J. G., Hale, N., Spector, A. A., & Coryell, W. H. (2010). Neuroticism but not omega-3 fatty acid levels correlate with early responsiveness to escitalopram. Annals of Clinical Psychiatry, 22, 157–163.

    PubMed  Google Scholar 

  • File, S. E., Cheeta, S., & Kenny, P. J. (2000). Neurobiological mechanisms by which nicotine mediates different types of anxiety. European Journal of Pharmacology, 393(1–3), 231–236.

    Article  PubMed  Google Scholar 

  • File, S. E., Kenny, P. J., & Ouagazzal, A. M. (1998). Bimodal modulation by nicotine of anxiety in the social interaction test: Role of the dorsal hippocampus. Behavioral Neuroscience, 112, 1423–1429.

    Article  PubMed  Google Scholar 

  • Fries, E., Hellhammer, D. H., & Hellhammer, J. (2006). Attenuation of the hypothalamic–pituitary–adrenal axis responsivity to the Trier Social Stress Test by the benzodiazepine alprazolam. Psychoneuroendocrinology, 31, 1278–1288.

    Article  PubMed  Google Scholar 

  • Furmark, T. (2009). Neurobiological aspects of social anxiety disorder. Journal of Psychiatry and Related Sciences, 46, 5–12.

    Google Scholar 

  • Goldman-Rakic, P. S., Castner, S. A., Svensson, T. H., Siever, L. J., & Williams, G. V. (2004). Targeting the dopamine D1 receptor in schizophrenia: Insights for cognitive dysfunction. Psychopharmacology, 174, 3–16.

    Article  PubMed  Google Scholar 

  • Gonzalez-Lima, F., & Bruchey, A. K. (2004). Extinction memory improvement by the metabolic enhancer methylene blue. Learning & Memory, 11, 633–640.

    Article  Google Scholar 

  • Gould, R. A., Otto, M. W., & Pollack, M. H. (1995). A meta-analysis of treatment outcome for panic disorder. Clinical Psychology Review, 15, 819–844.

    Article  Google Scholar 

  • Guastella, A. J., Richardson, R., Lovibond, P. F., Rapee, R. M., Gaston, J. E., Mitchell, P., et al. (2008). A randomized controlled trial of d-cycloserine enhancement of exposure therapy for social anxiety disorder. Biological Psychiatry, 63, 544–549.

    Article  PubMed  Google Scholar 

  • Haller, J., Bakos, N., Szirmay, M., Ledent, C., & Freund, T. F. (2002). The effects of genetic and pharmacological blockade of the CB1 cannabinoid receptor on anxiety. European Journal of Neuroscience, 16, 1395–1398.

    Article  PubMed  Google Scholar 

  • Hariri, A. R., Goldberg, T. E., Mattay, V. S., Kolachana, B. S., Callicott, J. H., Egan, M. F., et al. (2003). Brain-derived neurotrophic factor val66met polymorphism affects human memory-related hippocampal activity and predicts memory performance. Journal of Neuroscience, 23, 6690–6694.

    PubMed  Google Scholar 

  • Herry, C., & Garcia, R. (2002). Prefrontal cortex long-term potentiation, but not long-term depression, is associated with the maintenance of extinction of learned fear in mice. Journal of Neuroscience, 22, 577–583.

    PubMed  Google Scholar 

  • Hofmann, S. G. (2007). Enhancing exposure-based therapy from a translational research perspective. Behaviour Research & Therapy, 45, 1987–2001.

    Article  Google Scholar 

  • Hofmann, S. G., Meuret, A. E., Smits, J. A. J., Simon, N. M., Pollack, M. H., Eisenmenger, K. C., et al. (2006). Augmentation of exposure therapy for social anxiety disorder with d-Cycloserine. Archives of General Psychiatry, 63, 298–304.

    Article  PubMed  Google Scholar 

  • Hofmann, S. G., Pollack, M. H., & Otto, M. W. (2006). Augmentation treatment of psychotherapy for anxiety disorders with d-cycloserine. CNS Drug Review, 12, 208–217.

    Article  Google Scholar 

  • Hofmann, S. G., Sawyer, A. T., Korte, K. J., & Smits, J. A. J. (2009). Is it beneficial to add pharmacotherapy to cognitive-behavioral therapy when treating anxiety disorders? A meta-analytic review. International Journal of Cognitive Therapy, 2, 160–175.

    Article  PubMed  Google Scholar 

  • Hofmann, S. G., & Smits, J. A. J. (2008). Cognitive-behavioral therapy for adult anxiety disorders: A meta-analysis of randomized placebo-controlled trials. Journal of Clinical Psychiatry, 69, 621–632.

    Article  PubMed  Google Scholar 

  • Hofmann, S. G., Smits, J. A. J., Asnaani, A., Gutner, C. A., & Otto, M. W. (2011). Cognitive enhancers for anxiety disorders. Pharmacology Biochemistry and Behavior, 99, 275–284.

    Article  Google Scholar 

  • Holmes, A., & Quirk, G. J. (2010). Pharmacological facilitation of fear extinction and the search for adjunct treatments for anxiety disorders–the case of yohimbine. Trends in Pharmacological Science, 31, 2–7.

    Article  Google Scholar 

  • Johannsen, S., Duning, K., Pavenstädt, H., Kremerskothen, J., & Boeckers, T. M. (2008). Temporal-spatial expression and novel biochemical properties of the memory-related protein KIBRA. Neuroscience, 155, 1165–1173.

    Article  PubMed  Google Scholar 

  • Junghanns, K., Tietz, U., Dibbelt, L., Kuether, M., Jurth, R., Ehrenthal, D., et al. (2005). Attenuated salivary cortisol secretion under cue exposure is associated with early relapse. Alcohol & Alcoholism, 40, 80–85.

    Article  Google Scholar 

  • Kaplan, G. B., Vasterling, J. J., & Vedak, P. C. (2010). Brain-derived neurotrophic factor in traumatic brain injury, post-traumatic stress disorder, and their comorbid conditions: Role in pathogenesis and treatment. Behavioral Pharmacology, 21, 427–437.

    Article  Google Scholar 

  • Klokk, M., Gotestam, K. G., & Mykletun, A. (2010). Factors accounting for the association between anxiety and depression, and eczema: The Hordaland health study (HUSK). BMC Dermatology, 10, 3.

    Article  PubMed  Google Scholar 

  • Kobayashi, K., Shimizu, E., Hashimoto, K., Mitsumori, M., Koike, K., Okamura, N., et al. (2005). Serum brain-derived neurotrophic factor (BDNF) levels in patients with panic disorder: As a biological predictor of response to group cognitive behavioral therapy. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 29, 658–663.

    Article  PubMed  Google Scholar 

  • Koo, M. S., Kim, E. J., Roh, D., & Kim, C. H. (2010). Role of dopamine in the pathophysiology and treatment of obsessive-compulsive disorder. Expert Review of Neurotherapeutics, 10, 275–290.

    Article  PubMed  Google Scholar 

  • Kremerskothen, J., Plaas, C., Büther, K., Finger, I., Veltel, S., Matanis, T., et al. (2003). Characterization of KIBRA, a novel WW domain-containing protein. Biochemical and Biophysical Research Communications, 300, 862–867.

    Article  PubMed  Google Scholar 

  • Kushner, M. G., Kim, S. W., Donahue, C., Thuras, P., Adson, D., Kotlyar, M., et al. (2007). d-cycloserine augmented exposure therapy for obsessive-compulsive disorder. Biological Psychiatry, 62, 835–838.

    Article  PubMed  Google Scholar 

  • Lebrón, K., Milad, M. R., & Quirk, G. J. (2004). Delayed recall of fear extinction in rats with lesions of ventral medial prefrontal cortex. Learning & Memory, 11, 544–548.

    Article  Google Scholar 

  • Lissek, S., Powers, A. S., McClure, E. B., Phelps, E. A., Woldehawariat, G., Grillon, C., et al. (2005). Classical fear conditioning in the anxiety disorders: A meta-analysis. Behaviour Research & Therapy, 43, 1391–424.

    Article  Google Scholar 

  • Lupien, S. J., Friocco, A., Wan, N., Maheu, F., Lord, C., Schramek, T., et al. (2005). Stress hormones and human memory function across the lifespan. Psychoneuroendocrinology, 30, 225–242.

    Article  PubMed  Google Scholar 

  • Marsicano, G., Moosmann, B., Hermann, H., Lutz, B., & Behl, C. (2002). Neuroprotective properties of cannabinoids against oxidative stress: role of the cannabinoid receptor CB1. Journal of Neurochemistry, 80(3), 448–456.

    Article  PubMed  Google Scholar 

  • Masdrakis, V. G., Markianos, M., Vaidakis, N., Papakostas, Y. G., & Oulis, P. (2009). Caffeine challenge and breath-holding duration in patients with panic disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 33, 41–44.

    Article  PubMed  Google Scholar 

  • McNamara, R. K., & Carlson, S. E. (2006). Role of omega-3 fatty acids in brain development and function: Potential implications for the pathogenesis and prevention of psychopathology. Prostaglandins, Leukotrienes and Essential Fatty Acids, 75, 329–349.

    Article  Google Scholar 

  • Milad, M. R., & Quirk, G. J. (2002). Neurons in medial prefrontal cortex signal memory for fear extinction. Nature, 420, 70–74.

    Article  PubMed  Google Scholar 

  • Milad, M. R., Vidal-Gonzalez, I., & Quirk, G. J. (2004). Electrical stimulation of medial prefrontal cortex reduces conditioned fear in a temporally specific manner. Behavioral Neuroscience, 118, 389–394.

    Article  PubMed  Google Scholar 

  • Momose, Y., Murata, M., Kobayashi, K., Tachikawa, M., Nakabayashi, Y., Kanazawa, I., et al. (2002). Association studies of multiple candidate genes for Parkinson’s disease using single nucleotide polymorphisms. Annals of Neurology, 51, 133–136.

    Article  PubMed  Google Scholar 

  • Morgan, M. A., Romanski, L. M., & LeDoux, J. E. (1993). Extinction of emotional learning: Contribution of medial prefrontal cortex. Neuroscience Letters, 163, 109–113.

    Article  PubMed  Google Scholar 

  • Morris, R. W., & Bouton, M. E. (2007). The effect of yohimbine on the extinction of conditioned fear: A role for context. Behavioral Neuroscience, 121, 501–14.

    Article  PubMed  Google Scholar 

  • Mystkowski, J. L., Mineka, S., Vernon, L. L., & Zinbarg, R. E. (2003). Changes in caffeine states enhance return of fear in spider phobia. Journal of Consulting and Clinical Psychology, 71, 243–50.

    Article  PubMed  Google Scholar 

  • Nardi, A. E., Valença, A. M., Nascimento, I., Freire, R. C., Veras, A. B., de-Melo-Neto, V. L., et al. (2008). A caffeine challenge test in panic disorder patients, their healthy first-degree relatives, and healthy controls. Depression and Anxiety, 25, 847–853.

    Article  PubMed  Google Scholar 

  • Nestler, E. J., Barrot, M., DiLeone, R. J., Eisch, A. J., Gold, S. J., & Monteggia, L. M. (2002). Neurobiology of Depression. Neuron, 34, 13–25.

    Article  PubMed  Google Scholar 

  • Nikolaus, S., Antke, C., Beu, M., & Müller, H. W. (2010). Cortical GABA, striatal dopamine and midbrain serotonin as the key players in compulsive and anxiety disorders–results from in vivo imaging studies. Reviews in the Neurosciences, 21, 119–139.

    Article  PubMed  Google Scholar 

  • Norberg, M. M., Krystal, J. H., & Tolin, D. F. (2008). A meta-analysis of d-cycloserine and the facilitation of fear extinction and exposure therapy. Biological Psychiatry, 63, 1118–1126.

    Article  PubMed  Google Scholar 

  • Olver, J. S., O’Keefe, G., Jones, G. R., Burrows, G. D., Tochon-Danguy, H. J., Ackermann, U., et al. (2009). Dopamine D1 receptor binding in the striatum of patients with obsessive-compulsive disorder. Journal of Affective Disorders, 114, 321–326.

    Article  PubMed  Google Scholar 

  • Otto, M. W., Basden, S. L., McHugh, R. K., Kantak, K. M., Deckersbach, T., Cather, C., et al. (2009). Effects of d-cycloserine administration on weekly non-emotional memory tasks in healthy participants. Psychotherapy & Psychosomatics, 78, 49–54.

    Article  Google Scholar 

  • Otto, M. W., McHugh, R. K., & Kantak, K. M. (2010). Combined pharmacotherapy and cognitive-behavioral therapy for anxiety disorders: Medication effects, glucocorticoids, and attenuated outcomes. Clinical Psychology: Science and Practice, 37, 91–103.

    Article  Google Scholar 

  • Otto, M. W., Tolin, D. F., Simon, N. M., Pearlson, G. D., Basden, S., Meunier, S. A., et al. (2010). Efficacy of d-cycloserine for enhancing response to cognitive behavioral therapy for panic disorder. Biological Psychiatry, 67, 365–370.

    Article  Google Scholar 

  • Pacher, P., Bátkai, S., & Kunos, G. (2006). The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacology Review, 58, 389–462.

    Article  Google Scholar 

  • Pakdel, R., & Rashidy-Pour, A. (2007). Microinjections of the dopamine D2 receptor antagonist sulpiride into the medial prefrontal cortex attenuate glucocorticoid-induced impairment of long-term memory retrieval in rats. Neurobiology of Learning and Memory, 37, 385–390.

    Article  Google Scholar 

  • Papassotiropoulos, A., Stephan, D. A., Huentelman, M. J., Hoerndli, F. J., Craig, D. W., Pearson, J. V., et al. (2006). Common Kibra alleles are associated with human memory performance. Science, 314, 475–458.

    Article  PubMed  Google Scholar 

  • Pollack, M. H., Otto, M. W., Roy-Byrne, P. P., Coplan, J. D., Rothbaum, B. O., Simon, N. M., et al. (2008). Novel treatment approaches for refractory anxiety disorders. Depression & Anxiety, 25, 467–476.

    Article  Google Scholar 

  • Pomara, N., Willoughby, L. M., Sidtis, J. J., Cooper, T. B., & Greenblatt, D. J. (2005). Cortisol response to diazepam: Its relationship to age, dose, duration of treatment, and presence of generalized anxiety disorder. Psychopharmacology, 178, 1–8.

    Article  PubMed  Google Scholar 

  • Porter, A. C., & Felder, C. C. (2001). The endocannabinoid nervous system: Unique opportunities for therapeutic intervention. Pharmacology & Therapeutics, 901, 45–60.

    Article  Google Scholar 

  • Powers, M. B., Smits, J. A., Otto, M. W., Sanders, C., & Emmelkamp, P. M. (2009). Facilitation of fear extinction in phobic participants with a novel cognitive enhancer: A randomizedplacebo controlled trial of yohimbine augmentation. Journal of Anxiety Disorders, 23, 350–356.

    Article  PubMed  Google Scholar 

  • Putman, P., Van Honk, J., Kessels, R. P., Mulder, M., & Koppeschaar, H. P. (2004). Salivary cortisol and short and long-term memory for emotional faces in healthy young women. Psychoneuroendocrinology, 29, 953–60.

    Article  PubMed  Google Scholar 

  • Quirk, G. J., Garcia, R., & González-Lima, F. (2006). Prefrontal mechanisms in extinction of conditioned fear. Biological Psychiatry, 60, 337–343.

    Article  PubMed  Google Scholar 

  • Quirk, G. J., Russo, G. K., Barron, J. L., & Lebron, K. (2000). The role of ventromedial prefrontal cortex in the recovery of extinguished fear. Journal of Neuroscience, 20, 6225–6231.

    PubMed  Google Scholar 

  • Rauch, S. L., Shin, L. M., & Phelps, E. A. (2006). Neurocircuitry models of posttraumatic stress disorder and extinction: Human neuroimaging research—past, present, and future. Biological Psychiatry, 60, 376–382.

    Article  PubMed  Google Scholar 

  • Ressler, K. J., Rothbaum, B. O., Tannenbaum, L., Anderson, P., Graap, K., Zimand, E., et al. (2004). Cognitive enhancers as adjuncts to psychotherapy: Use of d-cycloserine in phobic individuals to facilitate extinction of fear. Archives of General Psychiatry, 61, 1136–1144.

    Article  PubMed  Google Scholar 

  • Richardson, R., Ledgerwood, L., & Cranney, J. (2004). Facilitation of fear extinction by d-cycloserine: Theoretical and clinical implications. Learning & Memory, 11, 510–516.

    Article  Google Scholar 

  • Rohrer, T., von Richthofen, V., Schulz, C., Beyer, J., & Lehnert, H. (1994). The stress-, but not corticotropin-releasing hormone-induced activation of the pituitary–adrenal axis in man is blocked by alprazolam. Hormone and Metabolic Research, 26, 200–206.

    Article  PubMed  Google Scholar 

  • Roy-Byrne, P. P., & Cowley, D. S. (2002). Pharmacological treatments for panic disorder, generalized anxiety disorder, specific phobia, and social anxiety disorder. In P. E. Nathan & J. M. Gorman (Eds.), A Guide to Treatments That Work (2nd ed., pp. 337–365). New York, NY: Oxford University Press.

    Google Scholar 

  • Salín-Pascual, R. J., & Basañez-Villa, E. (2003). Changes in compulsion and anxiety symptoms with nicotine transdermal patches in non-smoking obsessive-compulsive disorder patients. Revista de Investigacion Clinica, 55, 650–654.

    PubMed  Google Scholar 

  • Sareen, J., Campbell, D. W., Leslie, W. D., Malisza, K. L., Stein, M. B., Paulus, M. P., et al. (2007). Striatal function in generalized social phobia: A functional magnetic resonance imaging study. Biological Psychiatry, 61, 396–404.

    Article  PubMed  Google Scholar 

  • Sawaguchi, T., & Goldman-Rakic, P. S. (1991). D1 dopamine receptors in prefrontal cortex: Involvement in working memory. Science, 251, 947–950.

    Article  PubMed  Google Scholar 

  • Schneider, A., Huentelman, M. J., Kremerskothen, J., Duning, K., Spoelgen, R., & Nikolich, K. (2010). KIBRA: A New Gateway to Learning and Memory? Frontiers in Aging & Neuroscience, 2, 4.

    Google Scholar 

  • Seamans, J. K., & Yang, C. R. (2004). The principal features and mechanisms of dopamine modulation in the prefrontal cortex. Progress in Neurobiology, 74, 1–58.

    Article  PubMed  Google Scholar 

  • Sen, S., Nesse, R. M., Stoltenberg, S. F., Li, S., Gleiberman, L., Chakravarti, A., et al. (2003). BDNF coding variant is associated with the NEO personality inventory domain neuroticism, a risk factor for depression. Neuropsychopharmacology, 28, 397–401.

    Article  PubMed  Google Scholar 

  • Siegmund, A., Köster, L., Meves, A. M., Plag, J., Stoy, M., & Ströhle, A. (2011). Stress hormones during flooding therapy and their relationship to therapy outcome in patients with panic disorder and agoraphobia. Journal of Psychiatric Research, 45, 339–346.

    Article  PubMed  Google Scholar 

  • Sklar, P., Gabriel, S. B., McInnis, M. G., Bennett, P., Lim, Y. M., Tsan, G., et al. (2002). Family-based association study of 76 candidate genes in bipolar disorder: BDNF is a potential risk locus. Brain-derived neutrophic factor. Molecular Psychiatry, 76, 579–593.

    Article  Google Scholar 

  • Soliman, F., Glatt, C. E., Bath, K. G., Levita, L., Jones, R. M., Pattwell, S. S., et al. (2010). A genetic variant BDNF polymorphism alters extinction learning in both mouse and human. Science, 327, 863–866.

    Article  PubMed  Google Scholar 

  • Soravia, L. M., Heinrichs, M., Aerni, A., Maroni, C., Schelling, G., Ehlert, U., et al. (2006). Glucocorticoids reduce phobic fear in humans. Proceedings of the National Academy of Sciences of the United States of America, 103, 5585–5590.

    Article  PubMed  Google Scholar 

  • Stein, D. J., Ipser, J. C., & Seedat, S. (2006). Pharmacotherapy for post traumatic stress disorder (PTSD). Cochrane Database System Review, 25, CD002795.

    Google Scholar 

  • Stein, D. J., & Ludik, J. (2000). A neural network of obsessive-compulsive disorder: Modelling cognitive disinhibition and neurotransmitter dysfunction. Medical Hypotheses, 55, 168–176.

    Article  PubMed  Google Scholar 

  • Stewart, R. E., & Chambless, D. L. (2009). Cognitive-behavioral therapy for adult anxiety disorders in clinical practice: A meta-analysis of effectiveness studies. Journal of Consulting & Clinical Psychology, 77, 595–606.

    Article  Google Scholar 

  • Storch, E. A., Murphy, T. K., Goodman, W. K., Geffken, G. R., Lewin, A. B., Henin, A., et al. (2010). A preliminary study of d-cycloserine augmentation of cognitive-behavioral therapy in pediatric obsessive-compulsive disorder. Biological Psychiatry, 68, 1073–1076.

    Article  PubMed  Google Scholar 

  • Ströhle, A., Stoy, M., Graetz, B., Scheel, M., Wittmann, A., Gallinat, J., et al. (2010). Acute exercise ameliorates reduced brain-derived neurotrophic factor in patients with panic disorder. Psychoneuroendocrinology, 35, 364–368.

    Article  PubMed  Google Scholar 

  • Timonen, M., Horrobin, D., Jokelainen, J., Laitinen, J., Herva, A., & Räsänen, P. (2004). Fish consumption and depression: The Northern Finland 1966 birth cohort study. Journal of Affective Disorders, 82, 447–452.

    PubMed  Google Scholar 

  • van der Wee, N. J., van Veen, J. F., Stevens, H., van Vliet, I. M., van Rijk, P. P., & Westenberg, H. G. (2008). Increased serotonin and dopamine transporter binding in psychotropic medication-naive patients with generalized social anxiety disorder shown by 123I-beta-(4-iodophenyl)-tropane SPECT. Journal of Nuclear Medicine, 49, 757–763.

    Article  PubMed  Google Scholar 

  • Ventriglia, M., Bocchio Chiavetto, L., Benussi, L., Binetti, G., Zanetti, O., Riva, M. A., et al. (2002). Association between the BDNF 196 A/G polymorphism and sporadic Alzheimer’s disease. Molecular Psychiatry, 7, 136–137.

    Article  PubMed  Google Scholar 

  • Vinod, K. Y., & Hungund, B. L. (2006). Role of the endocannabinoid system in depression and suicide. Trends in Pharmacological Sciences, 27, 539–545.

    Article  PubMed  Google Scholar 

  • Viveros, M. P., Llorente, R., Moreno, E., & Marco, E. M. (2005). Behavioural and neuroendocrine effects of cannabinoids in critical developmental periods. Behavioural Pharmacology, 16, 353–362.

    Article  PubMed  Google Scholar 

  • Walker, D. L., Ressler, K. J., Lu, K. T., & Davis, M. (2002). Facilitation of conditioned fear extinction by systemic administration or intra-amygdala infusions of d-cycloserine as assessed with fear-potentiated startle in rats. Journal of Neuroscience, 22, 2343–2351.

    PubMed  Google Scholar 

  • Wilhelm, S., Buhlmann, U., Tolin, D. F., Meunier, S. A., Pearlson, G. D., Reese, H. E., et al. (2008). Augmentation of behavior therapy with d-cycloserine for obsessive-compulsive disorder. American Journal of Psychiatry, 165, 335–341.

    Article  PubMed  Google Scholar 

  • Yang, Y. L., Chao, P. K., Ro, L. S., Wo, Y. Y., & Lu, K. T. (2007). Glutamate NMDA receptors within the amygdala participate in the modulatory effect of glucocorticoids on extinction of conditioned fear in rats. Neuropsychopharmacology, 32, 1042–1051.

    Article  PubMed  Google Scholar 

  • Yu, H., Wang, Y., Pattwell, S., Jing, D., Liu, T., Zhang, Y., et al. (2009). Variant BDNF Val66Met polymorphism affects extinction of conditioned aversive memory. Journal of Neuroscience, 29, 4056–4064.

    Article  PubMed  Google Scholar 

  • Yun, A. J., Doux, J. D., & Daniel, S. M. (2007). Brewing controversies: Darwinian perspective on the adaptive and maladaptive effects of caffeine and ethanol as dietary autonomic modulators. Medical Hypotheses, 68, 31–36.

    Article  PubMed  Google Scholar 

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Hofmann, S.G., Gutner, C.A., Asnaani, A. (2012). Cognitive Enhancers in Exposure Therapy for Anxiety and Related Disorders. In: Neudeck, P., Wittchen, HU. (eds) Exposure Therapy. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3342-2_6

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