NEUROSCIENCE

UNDERLYING ANXIETY
DISORDER
PRESENTER : DR.VIGNESH H

CHAIRED BY: DR.VIJAYAKRISHNAN Y

OVERVIEW

• Fear and Anxiety

• Fear circuitry
• Neural circuitry during acquisition and extinction of fear
• Neurochemical system in Anxiety Disorder
• Neuroimaging studies of Anxiety Disorder
FEAR AND ANXIETY

• Normal emotional response to potential or actual threat

• In Anxiety disorder, these responses are dysregulated in a manner that is disturbing to

one’s life
Fear
Specific set of emotion that are
elicited when confronts danger
Acute immediate response to
suddenly appearing imminent
danger
Acute response to proximal
threat
Response to a known, external
definite or non conflictual
threat
Anxiety
Brain state elicited by signal
that predict impending but not
immediately presenting danger
Sustained insidious response to
danger
Response to distal threat
Response to threat that is
unknown, internal ,vague and
conflictual
FEAR CIRCUITRY

• Amygdala plays critical role

• Amygdala consists of many sub nuclei

• Lateral nucleus of Amygdala –Primary sensory interface

Recieving information from thalamus and cortex
• Auditory, visual and somatic input converge in Lateral nucleus (LA)

• Olfactory input enters cortical and medial nuclei of amygdala via direct projection from
olfactory bulb

• Amygdalar projection of LA to Basal and Acessory basal nuclei & Central nuclei of Amygdala
• Basal nucleus –Intranuclear connection to other amygdalar nuclei and also share
prjection with orbital and medial Prefrontal cortex

• Central nucleus receive convergent input from multiple amygdala region and organise
behavioural response
Central nucleus project to nuclei in Hypothalamus, midbrain and medulla → mediate
Autonomic and behavioural response associated with fear
• Multiple areas of medial and orbital prefrontal cortex- modulate anxiety and other
emotional behaviors.

• Peripheral hormonal and autonomic rezponse to threat mediated by HPA axis and
sympathetic and parasympathetic ANS facilitate generation of adaptive response to threat
or stress
DURING ACQUISITION

• Projection from PL and thalamic nuclei → excited LA neurons

• Hippocampal projection → extinction of BA neurons
• LA and BA neuron activate CE output nuerons which project to
Hypothalamic and brainstem nuclei → mediate
fear expression
DURING EXTINCTION

• Hippocampal projection→ excitation of IL neurons & inhibition of BA neurons

• IL projection –Activate GABAergic ITC cell and suppresion of CE output neuron
• Results in lack of physiologic response
NEROCHEMICAL SYSTEM IN ANXIETY DISORDERS

Norepinephrine
Primarily released in cns from locus ceruleus
Responsible for regulating body’s behavioural and physiologic response to stress
Excessive, unrestrained NE system is associated with Anxiety disorder
Dysfunction of NE system –Demonstrated in Panic disorder and Phobia
• CRH
CRH –Principal component of response to stress
Driven by stress, hypothalamic level of CRH increase →HPA become active→ increased
level of cortisol
Activation of CRH neurons trigers fear related behaviors.
• Dopamine
Dopamine is released in response to acute stress in amygdala, nucleus accumbens, mPFC
Prefrontal dopamine neurons are involved in facilitating the extinction of conditioned fear
response
• Serotonin
Serotonin hypothesis: anxiogenic action on PFC and amygdala
anxiolytic action on dorsal periacqueductal gray
• GABA
Studies of panic disorder patients –Reduced GABA and benzidiazepine binding in areas
such as cortex, hippocampus and insula

• Neurosteroids
Highly selective and positive allosteric modulators of GABA receptor, thereby making
potential anxiolytic
• Glutamate
Studies suggest that panic might arise from imbalance between GABA inhibition and
glutamate mediated excitation
• Others
Neuropeptide Y
Galanin
Cholecystokinin
Oxytocin
Arginine vassopressin
Endocannabinoid system
NEUROIMAGING STUDIES OF ANXIETY DISORDER

• Panic Disorder
Neuroimaging data suggests → associated with abnormalities in hippocampal at rest;
during panic attack reduced activity in widespread
cortical region including PFC
• Specific Phobia
Imaging finding –Activation of anterior paralimbic region
fMRI data suggests that amygdala hyperresponsivity occurs selectively to phobia relevant
stimuli
• Social Anxiety Disorder
Patient with SAD –altered response to social, but not non social stimuli
For eg. fMRI study found that hyperresponsivity of amygdala was selective for face stimuli
in patients with SAD
• Generalised Anxiety Disorder
It has been hypothesised that patient with GAD may display alterd BNST function in
addition to amygdala changes.
fMRI studies-Participant with GAD failed to normalise activation of ACC and mPFC
REFERENCE

• Kaplan and Sadock’s Comprehensive Textbook of psychiatry,10th edition

• Kaplan and Sadock’s Synopsis of psychiatry,11th edition
• The Brain and Behaviour ;An introduction to Behavioural anatomy,3rd edition
• Lisa M Shin,Israel Liberzon.The Neurocircuitry of fear stress and Anxiety
disorders.Neuropsychopharmacology reviews(2010)
• Elizabeth I martin,Kerry J Ressler.The Neurobiology of Anxiety disoerders:Brain
imaging,genetics and psychoneuroendocrinology.Psychiatr Clin North Am.2013