Lec 71 Bio basis of psychiatric disease Flashcards
What do we know about etiology/pathophysiology of psychiatric disorders?
- etiology unknown
- limited understanding of pathophysiology
What is basis of how we diagnose psychiatric disease?
based on clinical observation and symptom description
= descriptive and not etiologically based
What is RDoCs?
research domain criteria project
= focus on specific domains rather than traditional diagnostic categories
ex: negative valence systems; positive valence systems; cognitive systems; systems for social processes; arousal/regulatory processes
What is purpose of functional neuroimaging?
measure regional cerebral blood flow
measure glucose, oxygen metabolism
image receptors/transporters/NT systems
compare individuals at rest vs engaged in specific task
What are limitations of neuroimaging?
limited by physical properties of recording system and constraints of brain
small sample size = hard to apply to general population
expensive
What is the MAO deficiency hypothesis?
acute increase in synaptic MOAs by antidepressants produce 2ndary neuroplastic changes that involve transcriptional and translational changes
What is the DA hypothesis?
overactivity of DA neurons in mesolimbic pathway may mediate positive symptoms of psychosis
underactivity in mesocortical DA path may mediate negative, cognitive, affective symptoms of schizophrenia
What is mech of schizophrenia glutamate dysfunction?
hypofunction of NMDA glutamate receptor –> fail to put inhibitory brake on DA in limbic system
What is mech of MDD glutamate dysfunction?
chronic stress –> excess glutamate –> atrophy and death of neurons and glial cells
MDD:
- what can you see on structural imaging?
- what can you see on functional imaging?
- what change in NT?
structural: decreased volume of hippocampus PFC/OFC/ACC amygdala
functional: increased activity OFC/amygdala; ACC activity correlates with treatment response
NT: 5HT receptors altered
Schizophrenia:
- what can you see on structural imaging?
- what change in NT?
structural: enlarged ventricles, grey matter loss in dlPFC
NT: presynaptic DA synthesis and storage –> hyperactivity of DA in mesolimbic; hypoactivity in mesocortical
Social phobia: what can you see on functional imaging?
amygdala hyperactivity in response to harsh faces
Alzheimers: what can you see on functional imaging?
diagnositc amyloid deposition
What is major neurobio theory for pathogenesis of MDD?
MOAs, glutamate, BDNF
decreased cortical control over limbic output
increased cortisol
impaired plasticity
What is major neurobio theory for pathogenesis of panic disorder?
abnormally sensitive fear network including amygdala, PFC, insula, thalamus
decreased sensitivity in GABA system
