Richard L. Doolittle, PhD Vice Dean/Professor College of Health - - PowerPoint PPT Presentation

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

• ut 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

• ccasion 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)