Week 6 Transcripts.pdf

(107 KB) Pobierz
The  Addicted  Brain  Transcripts  –  Week  6  
Video  6.1  
 
Today  we  begin  the  very  important  topic  of  vulnerability,  and  this  lecture  will  
include  an  overview  of  things  we’ll  discuss  in  more  detail  in  later  lectures.    
 Vulnerability  addresses  the  question  of  will  I  become  an  addict,  or  will  you  become  
an  addict?  Let’s  revisit  this  image  from  week  one.  The  image  shows  the  same  person  
before  and  after  becoming  involved  with  methamphetamine.  Becoming  involved  
with  drugs  is  a  very  serious  and  often  deadly  proposition.  If  we  can  prevent  it,  we  
must  try.  Thus,  the  study  of  vulnerability  is  very  important.  
 
If  we  compare  large  groups  of  drug  users  with  large  groups  of  non-­‐users,  we  see  
differences.  The  differences  associated  with  taking  drugs  are  called  risk  factors  or  
vulnerability  factors.  These  are  the  factors  that  appear  to  make  you  vulnerable  to  
drug  use.  We  don’t  have  a  complete  understanding  of  vulnerability.  We  can’t  write  
an  equation  for  and  precisely  determine  if  you  will  or  will  not  become  an  addict.  
Vulnerability  and  risk  are  tendencies  and  nothing  more.  
 Fortunately  there  are  also  protective  factors  that  we  can  also  uncover  by  comparing  
drug  users  with  nonusers.  
 
Why  do  we  care?  Why  do  we  want  to  identify  risk  factors  and  what  makes  people  
vulnerable?  Well,  the  obvious  answer  is  that  we  want  to  protect  ourselves  and  each  
other.  If  individuals  have  risk  factors,  they  can  assess  if  they  need  to  be  proactive  
and  self-­‐protective.  We  can  warn  and  help  friends  who  are  in  danger,  and  we  can  
also  try  to  compensate  for  risk  factors.  In  addition,  prevention  resources  can  be  
directed  at  the  most  vulnerable  populations  to  be  most  effective.  
 So  there  are  many  reasons  to  identify  the  risk  factors  that  we  face.  
   
What  are  these  vulnerability  or  risk  factors?  An  important  one  is  our  biology.  Do  
members  of  a  family  take  drugs?  Are  there  inherited  factors?  We  will  discuss  
heritability  factors,  but  let  me  say  in  advance  that  inherited  risk  is  not  fully  
determining.  If  your  parents  were  drug  addicts,  it  does  not  mean  for  certain  that  you  
The  Addicted  Brain  Transcripts  -­‐  Week  6  
will  become  an  addict.  It  seems  that  genetics  have  about  a  50%  influence  on  the  
process  of  addiction.  This  knowledge  comes  from  detailed  studies  of  genetics  and  
drug  abuse.  
 
The  personality  and  overall  health  of  the  person  can  contribute  to  vulnerability.  It’s  
known  that  comorbid  or  coexisting  health  problems  often  occur  at  the  same  time  as  
drug  addiction  and  they  likely  influence  drug  taking.    
Risk-­‐taking  and  impulsive  behavior  are  personality  traits  that  are  also  risk  factors.  
Finally,  the  environment  plays  a  very  major  role.  Are  drugs  available?  Is  there  peer  
pressure  or  stress?  
All  of  these  can  be  somewhat  interrelated.  
 
Let’s  consider  some  important  and  well-­‐appreciated  risk  factors.  There’s  genetic  
predisposition,  personality  traits  and  temperament,  the  age  at  first  exposure  to  
drugs,  coexisting  health  problems,  attempts  at  self-­‐medication,  and  impaired  
judgment,  which  can  be  caused  by  the  drugs  themselves.  All  of  these  will  be  
discussed  this  week  in  more  detail.  
 
What  about  environmental  risk  factors?    Well,  availability  of  drugs  is  a  big  one.  If  
drugs  weren’t  available,  there  wouldn’t  be  drug  addiction.  
And  let’s  not  forget  stress.  Stress  is  an  extremely  important  risk  factor.  
Social  status  can  affect  drug  taking,  particularly  when  it  involves  stress.  Peer  
pressure  in  an  adolescent  population  can  be  a  very  strong  risk  factor.  And  drug  
awareness,  even  advertising  for  legal  drugs,  can  be  a  risk  factor.  
 
What  about  protective  factors?  All  of  the  following  seem  to  be  involved  with  lower  
drug  use.  Self-­‐control,  academic  competence,  antidrug  information  in  schools,  
strong  positive  neighborhood  attachments,  actively  compensating  for  risk  factors,  
some  genetics  can  be  protective,  parents’  attitudes  and  the  kind  of  home  they  
provide  can  be  protective,  and  animal  studies  have  shown  us  that  enriched  
environments  can  be  protective  as  well.    In  the  home,  enforcement  of  limits  and  
The  Addicted  Brain  Transcripts  -­‐  Week  6  
discipline,  forming  strong  bonds  with  children,  and  monitoring  children  seem  to  
help.  It's  comforting  to  know  that  we  can  take  active  steps  to  reduce  risk.  
All  of  these  factors  will  say  a  lot  about  who  can  potentially  become  an  addict.  
Please  don’t  forget  to  examine  the  review  questions  at  the  end  of  this  lecture.  
 
 
Video  6.2  
 
In  the  last  lecture,  I  showed  you  a  list  of  some  of  the  biological,  physiological,  and  
developmental  risk  factors  that  have  been  discovered.  Today,  we  are  going  to  look  at  
genetic  predisposition  in  greater  detail.  
 
It  is  clear  that  genetics  do  contribute  to  the  risk  for  drug  addiction.  Stated  simply,  
this  means  that  if  your  parents  or  other  family  members  have  abused  or  are  abusing  
drugs,  then  the  chances  or  the  risk  that  you  will  also  abuse  drugs  increases.  
 
The  best  data  for  this  comes  from  what  we  call  cross  adoption  studies.  Sons  of  
alcoholics  adopted  at  birth  to  nonalcoholic  families  have  a  fourfold  greater  
probability  of  becoming  alcoholic  than  their  stepbrothers.  Conversely,  sons  of  
nonalcoholic  parents  adopted  and  raised  by  alcoholic  families  did  not  tend  to  
become  alcoholics  even  when  their  stepbrothers  did.  
 
These  studies  and  a  large  number  of  many  other  studies  like  them,  indicate  that  
genes  are  involved  in  becoming  a  drug  addict.  But  it's  also  been  shown  that  genes  do  
NOT  totally  determine  your  drug-­‐related  life.  They  can  influence  drug  taking  but  
they  do  not  by  themselves  fully  determine  it.  You  cannot  get  away  with  saying  that  I  
take  drugs  simply  because  my  parents  do  or  did.  
 
Let’s  continue  to  talk  about  genetics.  We  have  talked  about  the  fact  that  genes  are  
found  in  DNA,  which  is  found  in  chromosomes.  
 
The  Addicted  Brain  Transcripts  -­‐  Week  6  
A  mutation  is  a  change  in  the  DNA  sequence.  It  could  be  a  change  in  a  single  
nucleotide,  a  duplication  of  a  sequence,  an  insertion  of  a  sequence,  a  deletion  of  a  
sequence,  or  a  copy  or  repair  error.  
 
Mutations  can  have  an  affect  on  function.  This  isn’t  surprising  because  a  mutation  in  
a  gene  is  likely  going  to  affect  the  protein  made  from  it.    There  can  be  a  loss  of  
function,  which  means  that  the  gene  product  has  no  or  a  lesser  function  as  a  result  of  
the  mutation.  
 
There  can  be  a  gain  of  function  where  the  new  product  has  an  improved  function.  
The  mutation  can  result  in  a  dominant  negative,  which  means  that  the  gene  product  
antagonizes  the  original  gene  and  its  product.  
 A  lethal  mutation  leads  to  the  death  of  an  individual,  and  a  back  mutation  is  a  
mutation  that  results  in  the  original  gene.  
 
A  harmful  mutation  decreases  the  health  and  performance  of  the  individual.  A  
beneficial  mutation  does  the  opposite.  A  neutral  mutation  has  no  effect  on  the  
individual.  And  the  effect  of  mutation  might  be  mixed,  in  that  it  could  be  beneficial  in  
some  way  and  perhaps  harmful  in  another  way.  
 
We  will  be  using  the  word  polymorphism.  This  refers  to  the  simultaneous  existence,  
in  a  population,  of  different  mutations.  In  other  words,  your  genes  may  not  be  
exactly  the  same  as  mine  even  though  we  function  about  the  same.  These  mutations  
occurred  in  our  ancestors  and  are  passed  down.  And  your  ancestors  are  different  
from  mine.  
 
SNPs,  or  single  nucleotide  polymorphisms,  are  used  in  studies  of  heritability.  An  
example  of  a  SNP  is  shown  in  the  image.  Some  of  us  might  carry  the  GC  version  of  
the  gene  while  others  of  us  might  carry  the  AT  version  of  the  gene.    Obviously  the  
SNPs  we  are  considering  are  not  lethal,  because  those  having  them  would  die.    But  
The  Addicted  Brain  Transcripts  -­‐  Week  6  
SNPs  can  affect  the  function  of  the  protein  because  they  can  affect  the  makeup  and  
structure  of  the  protein.  
 
One  of  the  versions  of  the  protein  might  be  found  more  often  in  addicts,  for  example.  
In  that  case,  one  could  say  that  it  might  partly  cause  the  addiction.  It  would  be  at  
least  associated  with  addiction.  
 
Here  are  some  examples  of  SNPs  that  have  been  associated  with  addicts.  A  SNP  in  
the  mu  opiate  receptor  protein  is  found  more  frequently  in  a  group  of  heroin  
addicts.  A  SNP  occurring  in  a  dopamine  receptor  is  more  frequent  in  alcoholics.  It  is  
not  yet  clear  how  much  the  different  SNPs  influence  addiction  or  why  they  should.  
This  is  a  current  area  of  research.    Also  we  know  that  an  association  does  not  prove  
that  it’s  a  cause.  Nevertheless,  associations  of  SNPs  with  addiction  have  been  very  
useful  in  exploring  the  molecular  basis  of  the  disorder.  
 
 
Let’s  consider  the  genetics  of  nicotine  receptors  and  their  role  in  smoking.  In  week  
three,  I  mentioned  that  nicotine  receptors  were  composed  of  subunits,  each  made  by  
different  genes.  And  I  mentioned  that  nicotine  receptors  are  actually  receptors  for  
the  NT  acetylcholine.  This  image  from  NIDA  shows  bundles  of  five  subunits  in  a  
circle  where  the  open  core  represents  a  channel  for  ions.  This  is  just  a  rough  
schematic  of  the  receptors.      Note  that  there  are  different  kinds  of  subunits.  One  has  
alpha-­‐1  and  beta-­‐2,  another  is  Alpha  seven  and  so  forth.  
 
Each  of  these  multiple  subunits  are  produced  by  different  genes.  It’s  been  shown  
that  the  occurrence  of  a  certain  SNP  in  the  Alpha  five  subunit  is  associated  with  
pleasure  from  a  first  cigarette  and  with  increased  risk  of  dependence  among  early  
smokers.  So  here  is  a  link  between  the  composition  of  the  receptor  for  nicotine  and  
the  likelihood  that  someone  will  become  a  smoker.  It  isn’t  clear  yet  how  the  
occurrence  of  these  subunits  and  SNPs  create  the  vulnerability.    But  it’s  a  compelling  

Plik z chomika:

Inne pliki z tego folderu:

Inne foldery tego chomika:

Zgłoś jeśli naruszono regulamin