NEUROBIOLOGY OF

ANXIETY DISORDERS

By
Dr. Anna Saikrishna Yadav
PG - II
Dept of Psy
 What is Anxiety?
• Anxiety is a normal emotion under circumstances of
threat and is part of the evolutionary “fight or flight”
reaction of survival.

• There are many circumstances in which the presence

of anxiety is maladaptive or excessive and which
constitutes to a psychiatric disorder.
• Core symptoms of anxiety are excessive fear and
worry.
 Disorders under anxiety spectrum
• Generalized anxiety disorder
• Panic disorder
• Phobic anxiety disorder
 Psychosocial factors
• Diminished sense of control
• Stressful life events
NEUROANATOMY
• Anxiety disorders are due to disruption in the balance
of activity in the emotional centers of the brain.

• Emotional-processing brain structures historically are

referred to as the “limbic system”

• The amygdala is responsible for the expression of

fear and aggression as well as species-specific
defensive behavior.

• It plays a role in the formation and retrieval of

emotional and fear-related memories.
 NEUROPHYSIOLOGY

• Hippocampus is a limbic system structure.

• It has tonic inhibitory control over the hypothalamic

stress-response system and plays a role in negative
feedback for the HPA axis.
Increased NE
Increased CRH
Increased NE
Increased CRH
 NEUROGENETICS
• Panic Disorder (PD) is most heritable of the anxiety
disorders.

• First-degree relatives of patients who have PD have a

sevenfold increased (7X) likelihood for PD and also
have an increased risk for phobic disorders

• Polymorphisms in SLC6A4, the gene for the

serotonin transporter, also have been associated with
PD

Martin EI, Ressler KJ, Binder E, Nemeroff CB. The Neurobiology of Anxiety
Disorders: Brain Imaging, genetics, and psychoneuroendocrinology. Psychiatric
Clinics of North America. 2009;32(3):549–75
• Studies have shown that first-degree relatives of GAD
have elevated rates of anxiety disorders in general and
specifically increased risk for GAD

• A recent study of more than 3000 twin pairs found

modest familial aggregation of GAD with equal
heritability in males and females in same-sex or
opposite-sex twin pairs.

Martin EI, Ressler KJ, Binder E, Nemeroff CB. The Neurobiology of Anxiety
Disorders: Brain Imaging, genetics, and psychoneuroendocrinology. Psychiatric
Clinics of North America. 2009;32(3):549–75
• The analysis of phobic anxiety disorder implicated a
region on chromosome 16 near the gene encoding the
norepinephrine transporter.

• Other genes associated with SAD include (1) a functional

variant in ADRB1, the gene encoding the β1-adrenergic
receptor, and (2) two SNPs and a 3-SNP haplotype in
the gene for COMT in female patients who have Phobic
anxiety disorder

Martin EI, Ressler KJ, Binder E, Nemeroff CB. The Neurobiology of Anxiety
Disorders: Brain Imaging, genetics, and psychoneuroendocrinology. Psychiatric
Clinics of North America. 2009;32(3):549–75
 NEUROCHEMISTRY

System NT’s Properties

Noradrenergic Norepinephrine Fear conditioning and Stress
physiological responses
Serotonergic 5HT2A Anxiogenic Upregulation

5HT1A Anxiolytic Downregulation

HPA Axis Fear conditioning and Stress
Cortisol emotion
GABAnergic GABA Arousal and relaxation Stress

Glutamatergic Glutamate Anxiogenic Stress

 NEURORADIOLOGY
• fMRI study - The panic was associated with
significantly increased activity in the right amygdala.

• PET - Elevated glucose uptake in the amygdala,

hippocampus, thalamus, midbrain, caudal pons,
medulla, and cerebellum in anxiety disorders.

• Magnetic resonance spectroscopy (MRS) has

demonstrated decreased GABA concentrations in the
occipital cortex, ACC, and basal ganglia in anxiety
disorders
Etkin A, Wager TD. Functional neuroimaging of anxiety: A meta-analysis of
emotional processing in PTSD, social anxiety disorder, and specific phobia. American
Journal of Psychiatry. 2007;164(10):1476–88.
Shin LM, Liberzon I. The neurocircuitry of fear, stress, and anxiety disorders.
Neuropsychopharmacology. 2010 Jan; 35(1):169-91
Murphy CP,
Singewald N. Role of
micrornas in anxiety
and anxiety-related
disorders. Current
Topics in Behavioral
Neurosciences. 2019;
 References
1. Stahl, S.M. (2013) Stahl’s Essential Psychopharmacology:
Neuroscientific Basis and Practical Applications. 5th Edition,
Cambridge University Press, Cambridge.
2. Martin EI, Ressler KJ, Binder E, Nemeroff CB. The Neurobiology of
Anxiety Disorders: Brain Imaging, genetics, and
psychoneuroendocrinology. Psychiatric Clinics of North America.
2009;32(3):549–75
3. Etkin A, Wager TD. Functional neuroimaging of anxiety: A meta-
analysis of emotional processing in PTSD, social anxiety disorder, and
specific phobia. American Journal of Psychiatry. 2007;164(10):1476–
88.
4. Shin LM, Liberzon I. The neurocircuitry of fear, stress, and anxiety
disorders. Neuropsychopharmacology. 2010 Jan; 35(1):169-91
5. Murphy CP, Singewald N. Role of micrornas in anxiety and anxiety-
related disorders. Current Topics in Behavioral Neurosciences. 2019;
• Thank you