BIOLOGY OF ANXIETY Ken Coll, MD

Objectives/Disclosures Review the basic neuroscience of fear and anxiety Correlate pragmatic clinical interventions with the underlying biological processes Through exploration of the biology of anxiety, identify potential avenues for additional treatment modalities No Disclosures/Conflicts

Anxiety is an Elephant

STARTLE EAR PONS MOTOR

Central Nucleus of the Amygdala CONDITIONED FEAR Light Central Nucleus of the Amygdala Basolateral Amygdala Shock

Sweat, CV, BP, Pupil Dilate Lateral Hypo Sweat, CV, BP, Pupil Dilate Parabrachial Nuc- respiratory Dorsal Mot Nuc/Nuc Ambig Urination/def Central Amygdala VTA/LC/BF Vigilant Arouse Paravent Nuc Hormone release Central Gray Freeze, pain Retic Nuc of Pons Startle Trigeminal N Facial N Fear Face

Fear- Enhanced Startle Light Central Nucleus of the Amygdala Basolateral Amygdala Shock EAR PONS MOTOR

Fear Enhanced Startle

Sweat, CV, BP, Pupil Dilate Lateral Hypo Sweat, CV, BP, Pupil Dilate Parabrachial Nucleus Respiratory Dorsal Mot Nuc/Nuc Ambig Urination/def Central Amygdala VTA/LC/BF Vigilant Arouse Paravent Nuc Hormone Release Central Gray Freeze, Pain Retic Nuc of Pons Startle Trigeminal N Facial N Fear Face

CONDITIONED FEAR AND SUSTAINED FEAR Bed Nucleus of the Stria Terminalis Light Basolateral Amygdala Shock Central Nucleus of the Amygdala Light and shock signals from sensory centers

Sweat, CV, BP, Pupil Dilate Lateral Hypo Sweat, CV, BP, Pupil Dilate Parabrachial Nuc- Respiratory Dorsal Mot Nuc/Nuc Ambig Urination/def Bed Nucleus Stria Terminalis VTA/LC/BF Vigilant Arouse Paravent Nuc Hormone release Central Gray Freeze, pain Retic Nuc of Pons Startle Trigeminal N Facial N Fear Face

Michael Davis, Emory University

CONDITIONED FEAR AND SUSTAINED FEAR (Anxiety) Bed Nucleus of the Stria Terminalis Light Basolateral Amygdala Shock Central Nucleus of the Amygdala EAR PONS MOTOR

Worry Enhanced Startle

TAKE HOME POINT The varying degree of fear and anxiety inherent in the anxiety disorders is correlated, at least in part, with the varying degree of activation between the amygdala and the bed nucleus of the stria terminalis

CORTEX AMYGDALA SENSORY THALAMUS SNAKE VS HOSE

TAKE HOME POINT The interpretation of the event in the cortex has a huge effect on the amount of activation in the amygdala/BNST

Sweat, CV, BP, Pupil Dilate Lateral Hypo Sweat, CV, BP, Pupil Dilate Parabrachial Nuc- Respiratory Dorsal Mot Nuc/Nuc Ambig Urination/def Bed Nucleus and Amygdala VTA/LC/BF Vigilant Arouse Paravent Nuc Hormone release Central Gray Freeze, pain Retic Nuc of Pons Startle Trigeminal N Facial N Fear Face

Sweat, CV, BP, Pupil Dilate Lateral Hypo Sweat, CV, BP, Pupil Dilate Parabrachial Nuc- Respiratory Dorsal Mot Nuc/Nuc Ambig Urination/def Bed Nucleus and Amygdala VTA/LC/BF Vigilant Arouse Paravent Nuc Hormone Release Central Gray Freeze, pain Retic Nuc of Pons Startle Trigeminal N Facial N Fear Face

Sweat, CV, BP, Pupil Dilate CORTEX Lateral Hypo Sweat, CV, BP, Pupil Dilate Parabrachial Nuc- Respiratory Dorsal Mot Nuc/Nuc Ambig Urination/def CORTEX CORTEX RTE Bed Nucleus and Amygdala CORTEX VTA/LC/BF Vigilant Arouse Paravent Nuc Hormone Release CORTEX CORTEX Inputs from the cortex can be received via CORTEX Central Gray Freeze, pain Retic Nuc of Pons Startle Trigeminal N Facial N Fear Face CORTEX CORTEX

FRONTAL LOBES/Cortex BNST and Amygdala HIPPOCAMPUS BRAINSTEM

FRONTAL LOBES/Cortex BNST and Amygdala HIPPOCAMPUS BRAINSTEM

Extinction

Hippocampus Amygdala BNST FEAR and ANXIETY

REDUCED FEAR and ANXIETY Hippocampus Amygdala BNST d-cycloserine at NMDA REDUCED FEAR and ANXIETY

Hippocampus Beta-blockers Amygdala BNST FEAR and ANXIETY

BETA and ALPHA BLOCKERS BNST and Amygdala BETA and ALPHA BLOCKERS LOCUS Coeruleus Norepinephrine

SSRIs, SNRIs, Buspar BNST and Amygdala Raphe SEROTONIN Nucleus GA BA Cortex

BNST and Amygdala Benzos and Beer GABA

BNST and Amygdala alpha 2 delta ligands Blocks Glutamate

Anxiety is an Elephant