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Lecture 17

HMB200 2014 Lecture 17.pdf

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University of Toronto St. George
Human Biology
John Yeomans

  Lecture  17:  Mental  Disorders  and  Limbic  Systems   - Amygdala  and  hippocampus  talks  to  each  other  by  way  of  limbic  system  pathways   - Important  in  anxiety  and  depression   Mental  Disorders   • Anxiety  Disorders   • Related  to  amygdala  and  tranquilizers   • Depression   • Involves  many  frontal  cortex  areas  (how  it  communicates  with  hippocampus  and  amygdala)   • Bipolar  Disorder  (Manic -­‐Depression)   • Delusion  thoughts  related  to  higher  human  executive  functions   • Schizophrenia   • Delusion  thoughts  related  to   higher  human  executive  functions   • Diagnostic  and  Statistical  Manual  (DSM5)  of  American  Psychiatry  Association   • Psychiatrists  reorganize  all  diagnosis  every  5  years           Anxiety  Disorders   • Phobias:  Specific  fears,  often  learned.  Treated  by  psychotherapy  “progre ssive  desensitization”.   • learned  fears  that  involved  particular  experience.  When  a  normal  fear  inhibits  your  ability  to  do  certain   things  =  phobia   • Treatment:  extinction  therapy  or  progressive  desensitization   • Exposed  to  it  more  and  more  =  desensitized   • Increase  realistic  experience  to  that  fear  to   de-­‐sensitize  Pavlovian  cues     • Pavlovian  process  =  extinction  therapy     • Can  eventually  come  closer  and  closer  to  contact  to  lose  the  fear   • No  drugs  required,  fast   •  Panic  attacks:  Severe  sympathetic  overreactions  to  uncomfortable  situations.  Usually  treated  with  tranquillizers  and   psychotherapy.   • severe  phobia  reaction  (increase  in  heart  rate,  freezing)   –  start  as  phobias,  then  become  generalized   (cannot  leave  house  anymore)   • Treatment:  drugs  –  benzodiazepines/tranquilizers   =  Theses  are  anxiolytic  drugs,  GABA  A  agonists   • inhibit  anxiety  producing  areas  (amygdala)  –  reducing  anxiety  by  slowing  activation  of  fear   systems  down   • Tranquilizers  reduce  discomforts  to  be  able  to  do  things   • benzodiazepines  cannot  be  used  for  long  term   –  become  addictive  and  less  effective  (short  term  is   most  successful)   •  Post-­‐traumatic  stress:  Fear  brought  on  by  specific   life  threatening  trauma,  e.g.,  violence  or  accident.  Nightmares.   • Long  term  experience  of  nightmares   à  taken  back  to  the  traumatic  experience  over  and  over  again   • Gross  over  activation  of  amygdala:   one  trail  learning  in  fear  conditioning  that  can  be  life  changing   • something  that  changes  life  experience   –  cannot  be  removed  by  extinction   • Therapy  would  involve  tranquilizers  and  other  strong  drug s  that  inhibit  the  amygdala   • Drugs  usually  taken  with  recreation  of  that  incident   • Amygdala:  when  you  think  you’re  guna  die,  it  has  struggles  to  bounce  back   • Powerful  learning  –  requires  more  treatment   •  Generalized  anxiety:  Persistent  worries  and  discomfort  w ith  life,  associated  with  depression.  Treated  with  SSRIs   or  tranquillizers.   • general  depression     • Feeling  life  is  hard  and  threatening   • SSRIs:  take  a  few  weeks  to  have  an  affect   –  involve  long  term  changes  in  brain  growth     Post-­‐traumatic  Stress  Disorder         - Close  eyes  to  relax:  you  get  flashback  instead  of  relaxing   - Intrusive  memories  come  back  instead  of  relaxing   - Hard  to  get  rid  of  memory   - Still  in  state  of  hypervigilance   –  its  going  to  happen  AGAIN   - Hypersensitive  to  startle   –  fear  potentiation  makes  they  hypervigilant  and  startle  sensitive   - Rapid  heart  rate,  increased  blood  pressure  (don’t  need  to  know  that  table)   - Mechanisms  of  fear  conditioning  studied  in  animals  are  highly  relevant  to  symptoms  in  PTSD   - PTSD  do  not  make  you  violent  directly,  it  makes  you  fearful   - Do  not  know  brain  region  detail       Anxiety  Disorders  II   • Repetitive  behaviors   • Different  set  of  symptoms  than  general  anxiety  disorders   • Obsessive-­‐Compulsive  Disorders:  Uncontrollable  and  irrational  desire  to  perform  repetitive  tasks,  e.g.   compulsion   to  washing,  or  checking  for  safety.  Overactivity  in  striatum .  Treated  with  SSRIs  or  neuroleptics.   • OCD:  uncontrollable  r epetitive  feelings  (accompanied  by  the  desire  to  do  something  about  it)   lead  to   repetitive  tasks   • Anxiety:  feelings  of  unsafe  and  not  protected   • Can  be  treated  by  antidepressants  or  neuroleptics   • Rational  and  normal  tasks,  irrational  part  is  doing  it  repetitive  times   • Ex.  Washing  hands  until  they  bleed,  wiping  table  until  colors  go  off   • Performing  the  ritual  provides  a  relief  for  anxiety,  but  doing  it  ove r  and  over  again,  it  gives  some  feeling  of   safety     • Dorsal  striatum  activation  by  dopamine   • D2  receptor  blocker  =  neuroleptic  =  reduce  ritualistic  behaviors  of  OCD   • However,  dorsal  striatum  is  important  for  habit  learning   • Performing  these  tasks  over  and  over   is  a  form  of  ritualized  habit   • Compulsion  to  do  this  habit  over  and  over  again   • Can  reduce  desire  to  perform  the  habit  by  blocking  habit  learning  in  dorsal  striatum   • Repetitions  seem  to  be  because  of  triggering  in  habit  memory  in  dorsal  striatum   • Because  dopamine  is  involved  in  addiction  and  in  this  type  of  anxiety  disorder   • There  is  an  activation  associated  with  addiction     • Use  substances  to  cope  with  depression   • Depression-­‐anxiety  complex   • Tourette’s  Syndrome:  Uncontrollable  tics /twitches,  either  motor  or  verbal.  Treated  with  neuroleptics.   • Tourette:  motor  tics  that  pull  arms  are  performed  over  and  over  again   –  motor  twitch  –  uncontrollable   • Need  a  conscious  effort  to  turn  off  the  tics   • Not  an  intellectual  disorder  or  a  distortion  of  reality   • Just  feel  more  comfortable  if  you  can  perform  tics   • Verbal  tics:  repetitive  swearing   • Can  still  be  perfectly  normal  people,  can  function   • Striatal  activation  that  is  made  more  comfortable  when  these  behaviors  are  performed   repetitively     • Can  be  controlled         Frontal  Cortex  and  Emotions   • Important  in  long  term  executive  functions  (long  term  evaluation  of  life  successes  and  failures)   • Right  front  cortex:  more  involved  with  depression   • Weak  lateralization  of  emotions  in  right  frontal  cortex.   • Left  frontal  cortex:  more  involved  in  social  behavio r  (more  sociable  and  friendly  cortex)   • Slight  difference  only,  not  totally  committed  to  each  hemisphere   • Changed  greatly  during  depression   • Increase  in  activity  during  depression   • Orbital,  medial  prefrontal  and  cingulate.   • Frontal  cortex  and  temporal  lobe  (amyg dala  and  temporal  lobe)  most  important   • Long  term  respond  to  emotions   • Immediate  responses  to  anxiety  and  stress   • Frontal  cortex:  long  term  evaluation  in  success  and  failures,  overall  feelings  of  how  you  are  doing  in  life   • Conscious  processing  of  rewards  and  p unishers.   • Important  in  depression  (fMRI)  and  SSRI  antidepressant  actions.   • Reduction  in  activity  when  given  SSRIs   • Long-­‐term  planning  of  emotions,  motives  and  actions.     Subcortex  and  Emotions   • Oldest  parts  of  limbic  system,  sometimes  called  extended  amygdala.   • Amygdala,  BNST,  Basal  Forebrain  (Olfactory  tubercle,  Septum  and  Basal  N.),  N.  Accumbens.   • Responsible  for:  Fear,  sex  and  maternal,  emotion  learning,  and  reward  learning.     Depression   • 2  major  areas  that  are  activated  (important  in  depressive  symptoms):     1) Frontal  Cortex  areas     2) Temporal  lobe  areas  (hippocampus,  amygdala)   - important  for  long  term  response  to  emotions  and  immediate  response  to  anxiety  and  stress   • Irrational  feelings  of  failure  and  hopelessness  (brain  change  –  change  in  evaluation  of  success  and  fail ure),  loss  of   appetites,  loss  of  energy,  sleep  disorders.   • Food,  sex,  friends  can  no  longer  provide  joy     • People  with  depression  have  trouble  sleeping   • Loss  of  energy,  don’t  sleep  enough,  dont  want  to  get  up  in  the  morning,  and  want  to  sleep  all  day   • Constant  sleep  disorder?  Sleep  disorders  can  be  treated  with  light   • Treated  with  selective  serotonin  reuptake  inhibitors,  benzodiazepines,  and/or  cognitive  psychotherapy.  Also,  MAO   inhibitors  and  tricyclic  antidepressants.   • Benzodiazepines  –  makes  you  feel  less  anxio us,  less  concerned  of  things  that  bother  you   –  temporary  relief   • SSRI  -­‐  Serotonin  reuptake  inhibitors:   build  up  serotonin  =  relief  of  symptom   • Do  not  work  well  for  mild  depression   • Only  work  well  for  serious  long  term  depression   • SSRIs  take  weeks  to  work.  Why?   • Take  a  few  weeks  to  work   • Boosting  serotonin  (happens  in  hours)   isn’t  really  a  solution   • In  order  to  get  SSRI  to  remove  symptom,  need  longer  term  growth  process   required  to  relieve  depression   • Not  just  serotonin,  its  something  triggered  and  activated  by  sero tonin   • Also  can  be  treated  with  electroconvulsive  therapy,  cingulotomy  or  anterior  cingulate  stimulation.   • Activation  of  frontal  cortex  areas  –  removes  long  term  feeling   • Electrical  stimulation  across  the  temples:   electroconvulsive  shock   • Produces  a  seizure,  but  patient  feels  immediately  better   • Passing  current  through  medial  frontal  cortex,  through  orbital  and  Cingular  cortex   –  relief  of  symptoms   • Stimulation  of  cingulate  and  frontal  cortex  is  important     Brain  Changes   • Increased  activity  in  amygdala,  mediodorsal   thalamus,  medial  orbitofrontal  cortex.   • Benzodiazepines  inhibit  amygdala  and  many  other  areas.   • Benzodiazepines  inhibit  amygdala  and  relieve  anxiety   • SSRIs  inhibit  orbitofrontal  and  anterior  cingulate  cortex.  Also,  activate  hypothalamus  feeding/energy  system   for   weight  loss.       • SSRI  and  cognitive  therapy  -­‐  produce  long  term  changes  in  frontal  cortex  areas   • Where  electric  compulsive  shock  targets   • Cingulate  orbital  areas  are  critical  in  storing  long  term  depressive  memories   • These  therapies  allow  immediate  feeling  be tter  (prevents  suicide),  but  has  side  effects   • Cutting  the  cingulate  out  also  removes  depressive  thoughts   –  but  have  side  effects   • Cingulate  lesions  block  pain  and  depression   • SSRI’s:  produce  changes  in  brain  growth   • These  antidepressants  increase  the  number  o f  neurons  produce  in  hippocampus  in  the  den
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