1. 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)

2. 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
Huntington’s disease
Autism
Schizophrenia
ADHD
Anxiety

3. 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

4. Depression: Neural changes
Change activity in
ventral frontal,
midfrontal,
dorsolateral prefrontal
amydgala

5. 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)

6. Relation between Depression and Stress
Stress “activates” depression in susceptible individuals
High levels of circulating cortisol in hospitalized depression cases and suicide victims

7. Dexamethasone suppresses waking ACTH release when given at night.

8. Relation between Depression & Sleep
Complete loss of SWS
Increased REM – decreased latency to 1st REM
Decreasing REM -> improved functioning
MAOi suppress REM

10. 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

11. OCD: Neural changes Corticostriatal loop:
increased activity in limbic cortex and basal ganglia

12. OCD: Treatment
Tricyclic antidepressants alleviate symptoms (particularly 5-HT)
Brain lesion

13. Tourette’s 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

14. Huntington’s disease:
single dominant gene (50% chance)
basal ganglia pathology (caudate nucleus, putamen)
mostly GABAergic neurons
starts at 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