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Transcript
Richard L. Doolittle, PhD
Vice Dean/Professor
College of Health Sciences and Techonology
RIT
“Like so many addicts, I'd thought that if I
could only sort out my life, I could then sort
out my drinking. It was a revelation to see
that it would be simpler the other way
around”
- Pete Townsend
“A person who drinks too much on
occasion is still the same person as when
sober. An alcoholic, a real alcoholic, is not
the same person at all. You can't predict
anything about them for sure except that
they will be someone you never met
before.”
- Raymond Chandler
NIAAA stats:
-  >51% of those >12 y.o. (120 mill) using; of
those, 7.7% (18 mill) met criteria for
substance abuser
-  > 100,000 people die each year due to
alcohol-related causes
-  >$180 Million in cost
Risk of alcoholism = genetic predisposition
+ environmental influences
ž Based
on:
•  Extended pedigree studies
– 4-7 fold increase in first-degree relatives
•  Twin studies
– Higher rate in identical vs dizygotic twins
•  Study of adopted children raised separately
from alcoholic parents
– Higher rate in this population
•  Gene discoveries?
ž Benefits
of genome discovery:
•  Identify those at risk
•  Better understanding of environmental factors
•  Could lead to better treatments/prevention
ž Animal
studies reveal multiple genes
responsible for vulnerability to
alcoholism – no single gene identified
Many investigators have stressed the
importance of the interaction between an
inherited biological vulnerability and
environmental risk factors for developing
alcohol use disorders
Balance of EXCITATORY and INHIBITORY
neuronal influences
GABA
Imbalance of excitatory/inhibitory NT
influences that impact behavioral change
ž Binge-Intoxication:
Positive reinforcement from consumption
ž Withdrawal, Negative Effect:
Shift from positive reinforcement to
negative reinforcement =
desire to avoid negative consequences of
withdrawal – change from impulsive to
compulsive
ž Preoccupation-Anticipation:
Craving and compulsive alcohol seeking
ž Binge-Intoxication
Activation of Mesolimbic Reward Pathway
- 
- 
Increase in dopamine – “feel good”
neurotransmitter; disinhibition
(engaged in all aspects of dependency?)*
Increase natural opioids
* George Koob, 2010
The pathway begins in the ventral
tegmental area (VTA) of the midbrain and
connects to the limbic system via the
nucleus accumbens, the amygdala, and the
hippocampus, as well as to the medial
prefrontal cortex
Engaged with “natural rewards”of life =
seeking food/water/reproduction
ž Withdrawal, Negative
Effect
Due to alcohol-induced neuro-adaptation/
neuroplasticity changes
Accompanied by decrease in dopamine
levels, decrease in serotonin levels,
increase in GABA influences (inhibitory)
+
Activation of HPA axis - CRF release
(stress)
ž Withdrawal, Negative
Effect
Move from impulsive to compulsive
behavior around alcohol use
ž Preoccupation, Anticipation, Craving
Continued down-regulation of NT with
neuroplasticity changes;maximum CRF/
stress response
(anxiety, agitation, panic, impulsivity, etc.)
“It is most absurdly said, in popular
language, of any man, that he is disguised
in liquor; for, on the contrary, most men are
disguised by sobriety”
Thomas de Quincy, Confessions of an
English Opium-Eater (1856)
ž Stronger
relationship between alcohol
consumption and aggression in subjects
with certain traits:
•  Antisocial personality
•  Alcohol dependency
•  Impaired cognitive function
•  Previous aggressive episodes
Still difficult to predict
Valerie Altounian, RIT Medical Illustration student
(now employed by American Assosiation for Advancement of SCIENCE
Journal)