Library 3 Neurophysiology of Anxiety

Marques AA, Bevilaqua MC, da Fonseca AM, et al. Gender differences in the neurobiology of anxiety: focus on adult hippocampal neurogenesis. Neural Plast. 2016;2016:5026713. Article

Salzman C, le Bars P, Kerrihard TN. Neurobiologic basis of anxiety and its treatment. Harv Rev Psychiatry. 1993;1(4):197-206. Abstract

Stolarska-Weryńska U, Biedroń A, Kaciński M. The links between neuropsychology and neurophysiology. Przegl Lek. 2016;73(3):187-90. Abstract

Vaidyanathan U, Nelson LD, Patrick CJ. Clarifying domains of internalizing psychopathology using neurophysiology. Psychol Med. 2012;42(3):447-59. Abstract

Vermetten E, Bremner JD. Circuits and systems in stress. I. Preclinical studies. Depression Anxiety. 2002;15:126-47. Abstract

Vermetten E, Bramner JD. Circuits and systems in stress. II. Applications to neurobiology and treatment in posttraumatic stress disorder. Depression Anxiety. 2002;16(1):14–38. Abstract

3.2 By Receptor

Acetylcholine Receptor

Muscarinic

Nicotinic

Picciotto MR, Lewis AS, van Schalkwyk GI, Mineur YS. Mood and anxiety regulation by nicotinic acetylcholine receptors: A potential pathway to modulate aggression and related behavioral states. Neuropharmacology. 2015;96(Pt B):235-43. Abstract

Alpha₄ Beta₂

Alpha₆ Beta₂

AMPA Receptor

Calcium Channel Receptor

Alpha₂ Delta

Metabotropic

Cannabinoid Receptor

CB₁

CB₂

GPR55

Chemokine Receptor

Chloride Channel Receptor

Cholecystokinin Receptor

Cortioctropin Receptor

Dopamine Receptor

DRD1

DRD2

DRD3

GABA Receptor

Benzodiazepine

Almeida-Suhett CP, Prager EM, Pidoplichko V, et al. Reduced GABAergic inhibition in the basolateral amygdala and the development of anxiety-like behaviors after mild traumatic brain injury. PLoS One. 2014;9(7):e102627. Abstract

Atack JR. The benzodiazepine binding site of GABA(A) receptors as a target for the development of novel anxiolytics. Expert Opin Investig Drugs. 2005;14(5):601-18. Abstract

Chhatwal JP, Myers KM, Ressler KJ, Davis M. Regulation of gephyrin and GABAA receptor binding within the amygdala after fear acquisition and extinction. J Neurosci. 2005;25(2):502-6. Abstract

Farb DH, Ratner MH. Targeting the modulation of neural circuitry for the treatment of anxiety disorders. Pharmacol Rev. 2014;66(4):1002-32. Article

Gafford GM, Ressler KJ. GABA and NMDA receptors in CRF neurons have opposing effects in fear acquisition and anxiety in central amygdala vs. bed nucleus of the stria terminalis. Horm Behav. 2015;76:136-42. Abstract

Trincavelli ML, Da Pozzo E, Daniele S, Martini C. The GABAA-BZR complex as target for the development of anxiolytic drugs. Curr Top Med Chem. 2012;12(4):254-69. Abstract

GABA_A

GABA_A-p

GABA_B

Glucagon Receptor

Glycine Receptor

Histamine Receptor

H₁

H₂

Kainate Receptor

Melatonin Receptor

Motilin Receptor

Neurokinin Receptor

NK₁

Neuropeptide Y Receptor

NMDA Receptor

Davis M. NMDA receptors and fear extinction: implications for cognitive behavioral therapy. Dialogues Clin Neurosci. 2011;13(4):463-74. Article

Davis M, Walker DL, Myers KM. Role of the amygdala in fear extinction measured with potentiated startle. Ann N Y Acad Sci. 2003;985:218-32. Abstract

Davis M. Role of NMDA receptors and MAP kinase in the amygdala in extinction of fear: clinical implications for exposure therapy. Eur J Neurosci. 2002;16(3):395-8. Abstract

Walker DL, Davis M. The role of amygdala glutamate receptors in fear learning, fear-potentiated startle, and extinction. Pharmacol Biochem Behav. 2002;71(3):379-92. Abstract

Metabotropic

Opioid Receptor

Mu₁

Mu₂

Kappa

Van’t Veer A, Carlezon WA. Role of kappa-opioid receptors in stress and anxiety-related behavior. Psychopharmacology (Berl). 2013;229(3):435-52. Article

Kappa₁

Kappa₂

Kappa₃

Delta

Nociceptin (Orphanin, ORL-1)

Oxytocin Receptor

P2X Receptor

Potassium Channel Receptor

PPAR-a (Peroxisome Proliferator-Activated Receptor-alpha) Receptor

Secretin Receptor

Serine Receptor

Seratonin Receptor

5-HT_1a

5-HT_1b

5-HT_1d

5-HT_2a

5-HT_2b

5-HT_2c

5-HT₃

5-HT₄

5-HT_5a

5-HT₆

5-HT₇

Tokarski K, Kusek M, Sowa J, Bobula B. Possible involvement of 5-HT₇ receptor in pathophysiology of affective disorders and action of antidepressant drugs. Postepy Hig Med Dosw (Online). 2014;68:1104-13. Abstract

Sigma Receptor

Sodium Channel Receptor

Somatostatin Receptor

TRPV₁ (Transient Receptor Potential Vanillioid₁) channel Receptor

Chahl LA. TRP channels and psychiatric disorders. Adv Exp Med Biol. 2011;704:987-1009. Abstract

Nazıroğlu M, Demirdaş A. Psychiatric disorders and TRP channels: focus on psychotropic drugs. Curr Neuropharmacol. 2015;13(2):248-57. Article

Vasoactive Intestinal Peptide Receptor

Vasopressin Receptor

3.3 By Pharmacokinetic / Pharmacodynamic Enzymes – Genetics

1A2

2A6

2B6

2C8

2C9

2C19

2E1

3A4

3A5

3A7

ApoE

UGT

UGT 1A4

UGT 1A6

UGT 2B7

UGT 2B15

UGT 2B17

COMT

Epigenetics

3.4 By Endogenous Neuro Transmitters

Adenosine

Agouti-Related Peptide

ATP

BDNF

Bombesin

Calcitonin Gene-Related Peptide

α-CGRP

β-CGRP

Cannabinoids

Andanamide

Cytokines

Elements

Calcium

Chloride

Magnesium

Sodium

Zinc

GABA

Davis M, Myers KM. The role of glutamate and gamma-aminobutyric acid in fear extinction: clinical implications for exposure therapy. Biol Psychiatry. 2002;52(10):998-1007. Abstract

Galanin

Ghrelin

Hormones

Adrenocorticotropic hormone

Anabolic Steroids

DHEA

Testosterone

Corticosteroids

Estrogens

Growth Hormone

Oxytocin

Prolactin

Somatostatin

Thyroid Hormone

Vasopressin

Leptin

Monoamines

Acetyl – choline (ACh)

Aspartate

Dopamine

Zarrindast MR, Khakpai F. The modulatory role of dopamine in anxiety-like behavior. Arch Iran Med. 2015;18(9):591-603. Article

Epinephrine

GABA (Gamma – amino butyric acid)

Leonard BE. Sleep disorders and anxiety: biochemical antecedents and pharmacological consequences. J Psychosom Res. 1994;38 Suppl 1:69-87. Abstract

Lin HC, Mao SC, Gean PW. Block of gamma-aminobutyric acid-A receptor insertion in the amygdala impairs extinction of conditioned fear. Biol Psychiatry. 2009;66(7):665-73. Abstract

Prager EM, Bergstrom HC, Wynn GH, Braga MF. The basolateral amygdala γ-aminobutyric acidergic system in health and disease. J Neurosci Res. 2016;94(6):548-67. Article

Salzman C, Miyawaki EK, le Bars P, Kerrihard TN. Neurobiologic basis of anxiety and its treatment. Harv Rev Psychiatry. 1993;1(4):197-206. Abstract

Glutamate

Davis M, Myers KM. The role of glutamate and gamma-aminobutyric acid in fear extinction: clinical implications for exposure therapy. Biol Psychiatry. 2002;52(10):998-1007. Abstract

Glycine

Histamine

N – acetyl – aspartyl – glutamate (NAAG)

Melatonin

Norepinephrine

Charney DS, Woods SW, Nagy LM, et al. Noradrenergic function in panic disorder. J Clin Psychiatry. 1990;51 Suppl A:5-11. Abstract

Ferry B, Roozendaal B, McGaugh JL. Role of norepinephrine in mediating stress hormone regulation of long-term memory storage: a critical involvement of the amygdala. Biol Psychiatry. 1999;46(9):1140-52. Abstract

Ferry B, Roozendaal B, McGaugh JL. Involvement of alpha1-adrenoceptors in the basolateral amygdala in modulation of memory storage. Eur J Pharmacol. 1999;372(1):9-16. Abstract

Gazarini L, Stern CA, Carobrez AP, Bertoglio LJ. Enhanced noradrenergic activity potentiates fear memory consolidation and reconsolidation by differentially recruiting α1- and β-adrenergic receptors. Learn Mem. 2013;20(4):210-9. Abstract

Gazarini L, Stern CA, Piornedo RR, et al. PTSD-like memory generated through enhanced noradrenergic activity is mitigated by a dual step pharmacological intervention targeting its reconsolidation. Int J Neuropsychopharmacol. 2014;18(1). pii: pyu026. Article

Kalk NJ, Nutt DJ, Lingford-Hughes AR. The role of central noradrenergic dysregulation in anxiety disorders: evidence from clinical studies. J Psychopharmacol. 2011;25(1):3-16. Abstract

Neumeister A, Daher RJ, Charney DS. Anxiety disorders: noradrenergic neurotransmission. Handb Exp Pharmacol. 2005;(169):205-23. Abstract

Sullivan GM, Coplan JD, Kent JM, Gorman JM. The noradrenergic system in pathological anxiety: a focus on panic with relevance to generalized anxiety and phobias. Biol Psychiatry. 1999;46(9):1205-18. Abstract

Octopamine

Serine

Serotonin

Tyramine

Gastrins

Gastrin

Cholecystokinin

Gastrin Releasing Peptide

Neurohypophyseals

Neurophysin I

Neurophysin II

Neurokinins

Neurokinin A

Neurokinin B

Neuropeptide Y

Carvajal C, Dumont Y, Quirion R. Neuropeptide Y: role in emotion and alcohol dependence. CNS Neurol Disord Drug Targets. 2006;5(2):181-95. Abstract

Morales-Medina JC, Dumont Y, Quirion R. A possible role of neuropeptide Y in depression and stress. Brain Res. 2010;1314:194-205. Abstract

Wu G, Feder A, Wegener G, et al. Central functions of neuropeptide Y in mood and anxiety disorders. Expert Opin Ther Targets. 2011;15(11):1317-31. Abstract

Neuromedin U

Neurotensin

Neurotrophins

Brain-Derived Neurotrophic Factor (BDNF)

Nerve Growth Factor

Neurotrophin-3 (NT-3)

Neurotrophin 4/5 (NT-4/5)

Pancreatic polypeptide

Peptide YY

Secretins

Glucagon

Growth Hormone – Releasing Factor

Motilin

Secretin

Vasoactive intestinal peptide

Nitric oxide

Opioid

Dynorphin

Endorphin

Enkephalin

Tachykinins

Neurokinin A

Neurokinin B

Substance P

3.5 By Neuro Chemical Action

Agonists

Partial Agonists

Inverse Agonists

Antagonists

Agonist – Antagonists

Reverse Agonists

3.6 By CNS Loci

Brancati V, Vermetten M, Bremner MD. Functional neuroimaging studies in posttraumatic stress disorder: review of current methods and findings. Depression Anxiety. 2007;24:202-18. Abstract

Amygdala

Abiri D, Douglas CE, Calakos KC, et al. Fear extinction learning can be impaired or enhanced by modulation of the CRF system in the basolateral nucleus of the amygdala. Behav Brain Res. 2014;271:234-9. Article

Chhatwal JP, Myers KM, Ressler KJ, Davis M. Regulation of gephyrin and GABAA receptor binding within the amygdala after fear acquisition and extinction. J Neurosci. 2005;25(2):502-6. Abstract

Davis M. Role of NMDA receptors and MAP kinase in the amygdala in extinction of fear: clinical implications for exposure therapy. Eur J Neurosci. 2002;16(3):395-8. Abstract

Davis M, Walker DL, Myers KM. Role of the amygdala in fear extinction measured with potentiated startle. Ann N Y Acad Sci. 2003;985:218-32. Abstract

Gilpin NW, Herman MA, Roberto M. The central amygdala as an integrative hub for anxiety and alcohol use disorders. Biol Psychiatry. 2015;77(10):859-69. Abstract

Lin HC, Mao SC, Gean PW. Block of gamma-aminobutyric acid-A receptor insertion in the amygdala impairs extinction of conditioned fear. Biol Psychiatry. 2009;66(7):665-73. Abstract

Pissiota A, Frans O, Michelgård A, et al. Amygdala and anterior cingulate cortex activation during affective startle modulation: a PET study of fear. Eur J Neurosci. 2003;18(5):1325-31. Abstract

Prager EM, Bergstrom HC, Wynn GH, Braga MF. The basolateral amygdala γ-aminobutyric acidergic system in health and disease. J Neurosci Res. 2016;94(6):548-67. Article

Walker DL, Davis M. The role of amygdala glutamate receptors in fear learning, fear-potentiated startle, and extinction. Pharmacol Biochem Behav. 2002;71(3):379-92. Abstract

Bed Nucleus of the Stria Terminalis

Davis M, Shi C. The extended amygdala: are the central nucleus of the amygdala and the bed nucleus of the stria terminalis differentially involved in fear versus anxiety? Ann N Y Acad Sci. 1999;877:281-91. Abstract

Lebow MA, Chen A. Overshadowed by the amygdala: the bed nucleus of the stria terminalis emerges as key to psychiatric disorders. Mol Psychiatry. 2016;21(4):450-63. Article

Sahuque LL, Kullberg EF, Mcgeehan AJ, et al. Anxiogenic and aversive effects of corticotropin-releasing factor (CRF) in the bed nucleus of the stria terminalis in the rat: role of CRF receptor subtypes. Psychopharmacology (Berl). 2006;186(1):122-32. Article

Sink KS, Chung A, Ressler KJ, et al. Anxiogenic effects of CGRP within the BNST may be mediated by CRF acting at BNST CRFR1 receptors. Behav Brain Res. 2013;243:286-93. Article

Sink KS, Walker DL, Yang Y, Davis M. Calcitonin gene-related peptide in the bed nucleus of the stria terminalis produces an anxiety-like pattern of behavior and increases neural activation in anxiety-related structures. J Neurosci. 2011;31(5):1802-10. Article

Walker DL, Miles LA, Davis M. Selective participation of the bed nucleus of the stria terminalis and CRF in sustained anxiety-like versus phasic fear-like responses. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(8):1291-308. Article

Walker DL, Davis M. Role of the extended amygdala in short-duration versus sustained fear: a tribute to Dr. Lennart Heimer. Brain Struct Funct. 2008;213(1-2):29-42. Abstract

Core

Shell

Anterior Cingulate

Göttlich M, Krämer UM, Kordon A, et al. Decreased limbic and increased fronto-parietal connectivity in unmedicated patients with obsessive-compulsive disorder. Hum Brain Mapp. 2014;35(11):5617-32. Abstract

Hammer MB, Lorberbaum JP, george MS. Potential role of the anterior cingulate cortex in PTSD: Review and hypothesis. Depression Anxiety. 1999;9:1-14. Abstract

Pissiota A, Frans O, Michelgård A, et al. Amygdala and anterior cingulate cortex activation during affective startle modulation: a PET study of fear. Eur J Neurosci. 2003;18(5):1325-31. Abstract

Arcuate Nucleus

Basal Optic Nucleus of Meynert

Cortex

Frontal Cortex

Hippocampus

Marques AA, Bevilaqua MC, da Fonseca AM, et al. Gender differences in the neurobiology of anxiety: focus on adult hippocampal neurogenesis. Neural Plast. 2016;2016:5026713. Article

Shin LM, Shin PS, Hackers S, et al. Hippocampal function in posttraumatic stress disorder. Hippocampus. 2004;14(3):292-300. Abstract

Arcuate nucleus

Hypothalamus

Insula

Anterior Insula

Posterior Insula

Limbic

Gee DG, Fetcho RN, Jing D, et al. Individual differences in fronto-limbic circuitry and anxiety emerge with adolescent changes in endocannabinoid signaling across species. Proc Natl Acad Sci U S A. 2016;113(16):4500-5. Article

Jhung K, Ku J, Kim SJ, et al. Distinct functional connectivity of limbic network in the washing type obsessive-compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2014;53:149-55. Abstract

Locus ceruleus

Medial Septal Nucleus

Nucleus accumbens

Ahmadi H, Nasehi M, Rostami P, Zarrindast MR. Involvement of the nucleus accumbens shell dopaminergic system in prelimbic NMDA-induced anxiolytic-like behaviors. Neuropharmacology. 2013;71:112-23. Article

Core

Shell

Pallidum (Globus Pallidus)

Parietal Cortex

Prefrontal Cortex

Berkowitz RL, Coplan JD, Reddy DP, Gorman JM. The human dimension: how the prefrontal cortex modulates the subcortical fear response. Rev Neurosci. 2007;18(3-4):191-207. Abstract

Medial Prefrontal

Orbital Frontal

Raphe Nucleus

Caudal Dorsal

Rostral Dorsal

Spinal Cord

Chemoreceptor Trigger Zone

Dorsal Horn

Tegmental Area

Lateral

Ventral

3.7 By CNS Neural Pathways

Shin LM, Hanwerger K. Is posttraumatic stress disorder a stress-induced fear circuitry disorder? J Traum Stress. 2009;22(5):409-15. Abstract

Cholinergic System

Cortiocostriatal

Harrison BJ, Soriano-Mas C, Pujol J, et al. Altered corticostriatal functional connectivity in obsessive-compulsive disorder. Arch Gen Psychiatry. 2009;66(11):1189-200. Abstract

Frontal-Limbic

Beucke JC, Sepulcre J, Talukdar T, et al. Abnormally high degree connectivity of the orbitofrontal cortex in obsessive-compulsive disorder. JAMA Psychiatry. 2013;70(6):619-29. Abstract

Dopamine System

Mesocortico – pathway

Mesolimbic – pathway

Nigrostriatal – pathway

Tuberofundibular – pathway

Noradrenal System

Lateral tegmental field

Ponto – mesen – cephalo – tegmental complex

3.8 By Function (excepting impairment, non-medical use domains)

Overall

Quality of Life

Ability

Home

School

Work

Appetite

Coordination

Endurance

Energy

Enjoyment

Injury

Mood

Anger

Anxiety

Fear

Shin LM, Hanwerger K. Is posttraumatic stress disorder a stress-induced fear circuitry disorder? J Traum Stress. 2009;22(5):409-15. Abstract

Sadness

Outlook

Sexual Function

Sleep

Social Life

Somnolence

Strength

Weight

Withdrawal

3.9 By Anxiety Type

Generalized Anxiety Disorder (GAD)

Obsessive Compulsive Disorder (OCD)

Panic

Post Traumatic Stress Disorder (PTSD)

Social Anxiety Disorder (SAD)

Aouizerate B, Martin-Guehl C, Tignol J. Neurobiology and pharmacotherapy of social phobia. Encephale. 2004;30(4):301-13. Abstract

3.10 By Function: Executive Function

Acute

Acute Cognitive Effects

Acute Cognitive Effects: Memory

Acute Psychomotor Effects

Acute Psychomotor Effects: Driving

Chronic

Chronic Cognitive Effects

Chronic Cognitive Effects: Memory

Chronic Psychomotor Effects

Chronic Psychomotor Effects: Driving

3.11 By Function: Non-Medical Use

Addiction Liability

Craving

Gateway

Harmful Use

Liking

Overdose

3.12 By Exogenous Agent

Alcohol

Ciccocioppo R, Gehlert DR, Ryabinin A, et al. Stress-related neuropeptides and alcoholism: CRH, NPY, and beyond. Alcohol. 2009;43(7):491-8. Article

Gilpin NW. Corticotropin-releasing factor (CRF) and neuropeptide Y (NPY): effects on inhibitory transmission in central amygdala, and anxiety- & alcohol-related behaviors. Alcohol. 2012;46(4):329-37. Article

Silberman Y, Bajo M, Chappell AM, et al. Neurobiological mechanisms contributing to alcohol-stress-anxiety interactions. Alcohol. 2009;43(7):509-19. Article

Antipsychotics

Calcium Channel Agent

Cannabinoid

Elements

GABA Receptor Agent

See also Benzodiazepines Pharmacology – Neuropharmacology

See also Z drugs

Gas

Hallucinogen

Monoamine Reuptake Inhibitor

Buproprion

Mirtazepine

SNRI

Desvenlafaxine

Duloxetine

Milnacipran

Venlafaxine

SSRI

Citalopram

Escitalopram

Fluoxetine

Paroxetine

Sertraline

Vilazodone

TCA

Amitriptylline

Desipramine

Doxepin

Nortriptylline

Trazodone

Muscle Relaxant

Baclofen

Carisoprodol

Chlorzoxazone

Cyclobenzaprine

Metaxalone

Methacarbamol

Tizanidine

Nicotinic agonists

NMDA Agonist

NMDA Antagonist

Amantidine

Dextromethorphan

Ketamine

Memantine

Nitrous Oxide

Phencyclidine

NSAID

Opioid

Sodium Channel Agents

Carbamazepine

Lamotrigine

Lidocaine

Phenytoin

Topiramate

Zonisemide

Stimulants

Amphetamine

Armodafinil

Caffeine

Cocaine

Dextroamphetamine

Methamphetamine

Methylphenidate

Sánchez-Pérez AM, García-Avilés Á, Albert Gascó H, et al. Effects of methylphenidate on anxiety. Rev Neurol. 2012;55(8):499-506. Abstract

Modafinil

Phentermine

TRPV₁ Agent

Capsacin

3 Neurophysiology of Anxiety

3.1 Reviews