A framework for psychopathology

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A framework for psychopathology

• Symptoms
• Neural Causes (systems approach)
• A. Which neurotransmitters?
• B. Where in the brain? which methods measure
  it?
• Other causes Genetic, Social
• Neural Treatment
• A. Pharmacotherapy
• B. Brain stimulation, lesion
• Other (e.g., Cognitive behavioral therapy)

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Psychopathology

• Diseases with localized lesion
• Fronto-temporal dementia (last class)
• Orbitofrontal lesion (e.g, Traumatic brain
  injury)
• Strokes other lesions
• Lesion of medio-frontal structures Akinetic
  mutism
• Lesion of amygdala impaired processing of fear
• Diseases defined initially by their symptoms
• Depression
• Obsessive compulsive disorder
• Huntingtons disease
• Autism
• Schizophrenia
• ADHD
• Anxiety

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Depression Symptoms Possible substrates

• Cognitive processes
• Reduced concentration DLPFC
• impaired memory hippocampus
• Emotion/motivation/self Mid frontal, OFC
• Lack of energy
• Loss of interest
• Slowness of movement
• Mood Pessimism (depressive realism)
• Autonomic processes Ventral cingulate
• Changes in Apetite insula
• Reduced libido hypothalamus
• Changes in Sleep pattern
• (Shallow, Fragmented, Early REM onset)
• Increased cortisol levels

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Depression Neural changes

• Change activity in
• ventral frontal,
• midfrontal,
• dorsolateral prefrontal
• amydgala

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Depression Treatment

• Cognitive behavior therapy
• Pharmacotherapy
• SSRI, acts upon serotonin system
• MAOi,
• tricyclic antidepressants
• Electroconvulsive therapy
• Repeated Transcranial Magnetic Stimulation
• Deep Brain stimulation
• Sleep deprivation
• Selective (REM)
• Total (not feasible)

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Relation between Depression and Stress

• Stress activates depression in susceptible
  individuals
• High levels of circulating cortisol in
  hospitalized depression cases and suicide victims

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Dexamethasone suppresses waking ACTH release
when given at night.
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Relation between Depression Sleep

• Complete loss of SWS
• Increased REM decreased latency to 1st REM
• Decreasing REM -gt improved functioning
• MAOi suppress REM

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Obsessive-Compulsive Disorder (OCD)

• Symptoms
• Recurrent behaviors (compulsive)
• Recurrent thoughts (obsessive)
• People repeat things until they feel that they
  have gotten it right
• Frequently related to cleanliness or
  territoriality

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OCD Neural changes

• Corticostriatal loop
• increased activity in limbic cortex and basal
  ganglia

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OCD Treatment

• Tricyclic antidepressants alleviate symptoms
  (particularly 5-HT)
• Brain lesion

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• Tourettes syndrome
• Dysfunction of cortico-striatal loop
• number of D2 receptors in basal ganglia is
  increased as revelead by PET
• tics reduced by D2 antagonists (neuroleptics)
• abnormal cortico-striatal loop may explain
  aspects of repetitive behavior in OCD, FTD, autism

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Huntingtons disease single dominant gene (50
chance) basal ganglia pathology (caudate
nucleus, putamen) mostly GABAergic
neurons starts at 30- 45 years of age starts
with minor motor problems (twitches,
clumsiness) evolves into involuntary jerky
movements of eyes, legs also emotional changes
(depression, socially inappropriate
behavior) emotional changes sometimes precede
motor changes