Fear, Anxiety Disorders and Amygdala

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Fear, Anxiety Disorders and Amygdala

• PSY391S
• March 29, 2006
• John Yeomans

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Limbic System Anatomy

• Oldest areas of telencephalon, bordering
  diencephalon. Limbic means "border".
• Connections with olfactory and taste systems,
  hypothalamus (visceral emotional).
• Transition from subcortex (e.g. amygdala) to 3-4
  layered cortex (e.g. hippocampus) to 6-layered
  neocortex.
• Interconnections--"Papez Circuit"

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Amygdala and Conditioned Fear

• Unconditioned fear mediated through PAG.

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Extended Amygdala and Emotions

• Subcortical parts of limbic system.
• Amygdala, BNST, Basal Forebrain (olfactory
  tubercle, Ventral pallidum, septum and basal n.),
  n. accumbens.
• Fear and emotion learning (amygdala), sex and
  maternal behavior (medial amygdala, BNST, ventral
  pallidum), and reward learning (n. accumbens).

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Monogamous voles have more Vasopressin in their
Ventral Pallidum. Young et al.
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Bed Nucleus and Gender Identity

• Central n. of BNST is sexually dimorphic in
  humanslarger in males by 44.
• 6 transgendered males had smaller BNSTc.
• Not related to partner preference.
• No differences in MPO areas that are sexually
  dimorphic.
• Correlation, not causal link.

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Early Studies

• Temporal lobe lesions (Klüver-Bucy Syndrome) lead
  to tame monkeys, fearless and hypersexual.
• Temporal lobe epilepsy leads to emotional auras
  and behaviors.
• Stimulation of amygdala leads to attack, rage or
  positive affect.
• Stimulation of hippocampal region leads to
  experiential reports "deja vu".

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CS Tone, US shock
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LeDoux, Davis
Deep superior colliculus Startle Fear
Potentiation
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Fear Learning

• Unlearned emotional responses activated through
  PAG (central gray), SC, BNST and hypothalamus.
• Associations between CS and US occur in lateral
  and basolateral n.
• Fast CS auditory path via thalamus, slow CS path
  via auditory cortex.
• Context associations via hippocampus.

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/Deep SC
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Pharmacology of Fear and Anxiety

• Fear inhibited by benzodiazepines (GABAA
  agonists) in amygdala. Fear activated by
  glutamate.
• Panic activated by CCKB in amygdala.
• Stress/anxiety activated by CRH in BNST.
• Peripheral effects of stress hormones
  (CRH?ACTH?cortisol) and central effects on limbic
  system.

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Anxiety Disorders I

• Phobias Specific fears, often learned. Treated
  by psychotherapy progressive
  desensitization.
• Panic attacks Severe sympathetic overreactions
  to uncomfortable situations. Usually treated with
  tranquillizers and psychotherapy. Amygdala?
• Post-traumatic stress Fear brought on by
  specific trauma, e.g., violence or accident.
  Nightmares.
• Generalized anxiety Persistent excessive
  worries, associated with depression. Treated with
  SSRIs or tranquillizers.

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Posttraumatic Stress Disorder
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Anxiety Disorders II

• Obsessive-compulsive disorders Uncontrollable
  and irrational desire to perform repetitive
  tasks, e.g. washing, or checking for safety.
  Overactivity in striatum. Treated with
  neuroleptics.
• Tourettes Syndrome Uncontrollable tics, either
  motor or verbal. Treated with neuroleptics.

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Frontal Cortex and Emotions

• Orbital, medial prefrontal and cingulate.
• Conscious processing of rewards and punishers.
• Important in depression (fMRI) and SSRI
  antidepressant actions.
• Long-term planning of emotions, motives and
  actions.
• Weak lateralization of emotions in right frontal
  cortex.

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Areas Changed by Emotions (fMRI)
Yellow--Orbitofrontal Blue--Anterior
Cingulate Green--Posterior Cingulate Purple--Insul
a Red--Amygdala
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Depression

• Irrational feelings of failure and hopelessness,
  loss of appetites, loss of energy, sleep
  disorders.
• Treated with selective serotonin reuptake
  inhibitors, benzodiazepines, and/or cognitive
  psychotherapy.
• SSRIs take weeks to work, perhaps due to
  stimulation of neurogenesis in hippocampus.
• Often associated with generalized anxiety, and
  can be treated with tranquilizers short term.

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Brain Changes

• Increased activity in amygdala, mediodorsal
  thalamus, medial orbitofrontal cortex.
• Benzodiazepines inhibit amygdala and many other
  areas.
• SSRIs inhibit orbitofrontal cortex. Also,
  activate hypothalamus feeding/energy system for
  weight loss.
• Cognitive therapy inhibits anterior cingulate.
• Electroconvulsive shock still used occasionally,
  e.g. suicide, poor drug effect. Cingulotomy less
  often (pain and depression).

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Cingulate and Depression

• Cingulotomy (cutting fibers of anterior
  cingulate) relieves persistent pain and
  depression.
• Stimulation of subgenual anterior cingulate (Area
  25) relieves persistent depression in a few
  treatment-resistant people.

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Bipolar Disorder

• Manic-depression (now called bipolar disorder)
  results in severe mood swings from high to low.
• Usually cyclic, with shorter highs of great
  energy, self-confidence and destructive behaviors
  (spending, gambling, escapades), followed by
  longer periods of depression.
• Treated with lithium, which effectively smooths
  out highs and lows, but mechanism still unknown.
• Widespread brain changes.

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Schizophrenia

• Positive symptoms hallucination and delusions.
  Loss of contact with reality.
• Negative symptoms social withdrawal, poor
  grooming.
• Cognitive symptoms poor intellectual
  functioning.
• Positive symptoms treated by D2 blockers (typical
  neuroleptics).
• Negative symptoms also treated with atypical
  neuroleptics (e.g. clozapine) but mechanism still
  unknown.

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Brain Changes

• Dopamine system or receptors? Amphetamine
  psychosis.
• Phencyclidine (PCP) psychosis suggests that NMDA
  inhibition also important.
• Low frontal cortex activity.
• Changes in hippocampus organization.
• Reduction in cortical mass, and hippocampal/
  amygdala mass, with enlargement of ventricles.
• Causes? Strongly genetic, but many genes.
  EnvironmentDrug taking, prenatal viruses
  (cytokines slow brain development in pregnancy?)

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Male vs. Females

• More females than males have depression and some
  anxiety disorders.
• More males have schizophrenia, with earlier onset
  and greater severity.
• Estrogens may be protective factor, because some
  women get schizophrenia at menopause.