My  Experience  at  the  Massachusetts  Mental  Health  Center  and  My  Views  on  Mentorship,  Mental  Illness  and  Wellbeing    

My   research   within   the   Clinical   Research   Training   Program   at   Harvard   during   2001-­‐2003   was  conducted  at   the  Massachusetts  Mental  Health  Center   (MMHC).  Well-­‐known   for   its  pioneering   research   in  schizophrenia,  the  MMHC  has  produced  a  number  of  clinical  leaders  in  psychiatry.  It  may  come  as  a  surprise  to  many  that  the  MMHC  (previously  known  as  the  "Boston  Psychopathic  Hospital")  was  the  most  influential  sites  for  psychiatric  training  at  Harvard  for  over  90  years  until  it  was  it  closed  in  2003.    

A  special  tribute  was  made  at  the  center’s  closing  ceremony  in  honor  of  the  men  and  women  who,  at  various  points  in  their  lives,  have  dedicated  their  efforts  to  provide  long-­‐term  care  for  severely  ill  patients.  Those  who  have  crossed  path  here  reminisced  on  an  era  of  progress  in  which  Psychoanalysis  transitioned  to  Biological  Psychiatry.  The  MMHC  is  rather  a  small   institute,   largely  unknown  to  many  new  students   in   the  field,  but  it  was  an  important  driving  force  behind  this  shift  in  psychiatry.    The  links  below  contain  articles  on  a  heart-­‐warming  tribute  to  this  very  special  place  on  its  closing  day  in  2003.  http://www.1856.org/bloom/main.html   or   http://www.thisiscolossal.com/2012/03/bloom-­‐28000-­‐potted-­‐flowers-­‐installed-­‐at-­‐the-­‐massachusetts-­‐mental-­‐health-­‐center/  Potted  flowers  (28,000  of  them)  were  installed  throughout  the  MMHC.    A  picture  of  an  old  office  at  MMHC  that  resembles  my  old  office  (upper  left)  and  pictures  of  other  parts  of  the  building  for  the  closing  ceremony    

 

At  the  MMHC,  I  had  a  rare  opportunity  to  interact  with  unique  individuals  who  made  significant  impact  on  the  way   “mental   illness”   is   viewed.   These   individuals   also   gave  me   a   glimpse   into   the   inner  world   of   the  human   mind.   I   had   the   pleasure   to   meet   Dr.   Allan   Hobson,   a   pioneer   in   quantifying   conscious   and  unconscious  mental   events   during   sleep   associated  with   brain   states.     Through   conversing  with   him   and  studies  of  his  work,   I   saw   that  he  had  a  profound   insight   into   the  processes  of   the  mind  well  ahead  of  his  time.   I   also  had   the  honor   to  be  mentored  by  and  worked  with  Dr.  Joseph  Schildkraut,  who  many  consider  "the   father  of  psychopharmacology".  He   first  proposed  a  neurochemical  basis  of  psychopathology   through  his   treatise   on   the   norepinephrine   theory   of   depression.   I   saw   the   genius   in   Dr.   Schildkraut   and   gained  valuable  insight  into  the  neurochemical  basis  of  depression  through  working  with  him.    My  research  mentor  within  the  CRTP  was  Dr.  Alan  I.  Green,  who  then  was  a  Harvard  Professor  of  Psychiatry.  He  was  also  a  former  mentoree  and  a  long-­‐time  colleague  of  Dr.  Schildraut  at  the  MMHC.  Currently,  Dr.  Green  is  Department  Chair  and  Professor  of  Psychiatry,  Professor  of  Pharmacology  &  Toxicology  and  Director  of  SYNERGY  –  The  Dartmouth  Center  for  clinical  and  Translational  Science.    My  initial  meeting  with  Dr.  Green  came  about  almost  by  coincidence.  Before   I  arrived  at   the  MMHC,   I  had  daylong   interview  with  PIs  across  different  institutes  affiliated  with  Harvard.  Toward  the  end  of  the  day,  I  received  a  last-­‐minute  notice  that  Dr.  Green  wanted  to  talk  to  me.    A  national  leader  in  the  treatment  of  schizophrenia  and  co-­‐occurring  substance  use  disorder,  Dr.  Green  discussed  with  me  about  the  prevalence  of  substance  use  disorder  in  patients  with  schizophrenia  and  his  effort  trying  to  understand  whether  certain  abnormality  in  the  brain  reward  circuitry  of  these  patients  that  was  responsible  for  this  comorbidity,  known  among  clinicians  as  a  condition  that  was  “notoriously   difficult   to   treat”.     Coincidentally,   I   had   been   curious   for   some   time   about   a   possible   link  between  depression  and  schizophrenia,  because  my  Ph.D.  research  found  that  depression  involves  elevated  tonic   release  of   the  neurotransmitter   acetylcholine   in   the  nucleus   accumbens   (a   central   component  of   the  brain   reward  circuitry),  while   the  opposite   seems   to  occur   in   schizophrenia  –  patients  with   schizophrenia  are  known  to  have  a  deficiency  in  the  number  of  cholinergic  neurons  in  the  same  region.  As  fate  has  its  way,  I  subsequently  joined  Dr.  Green’s  group.      As  a  recent  Ph.D.  graduate  previously  engaged  in  laboratory  research,  coming  to  the  MMHC  has  broadened  my  view  of  the  complexity  of  psychiatric  practice  in  the  real  world.  I  found  that  many  of  the  patients  being  treated   had   multiple   psychiatric   disorders   that   compounded   their   problems   and   greatly   complicated  treatment.  But  there  was  one  thing  I  learned  that  stood  out  from  the  rest.    Through  my  conversations  with  Dr.  Green  I  gained  a  rare  insight  into  the  minds  of  patients  with  schizophrenia  whose  lives  were  transformed  in   an   amazing   way   after   receiving   clozapine   treatment.   Many   of   these   patients   transformed   from   being  withdrawn   and   incommunicable   to   being   delightfully   sociable,   as   well   as   having   a   great   sense   of   humor.    Interestingly,   these  patients  also  ceased   to  use  alcohol  and  substances.  On   the  other  hand,   I   could   feel   the  sense  of  hopelessness  in  those  who  did  not  get  well  despite  receiving  multiple  different  kinds  of  treatment.  I  could   also   imagine   the   confusion   and   despair   in   individuals   afflicted   by   similar   or   other   psychiatric  disorders,  many  of  whom  do  not  have  access  to  care  or  might  not  seek  care  for  a  variety  of  reasons,  including  lack  of  insight  into  their  own  conditions.    During  my   journey   trying   to  understand   the  body,  brain  and  mind,   I  met   individuals  whose  extraordinary  visions  and   life  philosophies  have  made   lasting   impression  on  me.  Among  them  was  Prof.  Stuart  T.  Hauser,  M.D.,   Ph.D.   former   President   of   Judge   Baker   Children   Center.   He   was   known   for   his   work   in   adolescent  development  and  his   focus  on  resilience   to  adversity.  An  excerpt   from  Harvard  Gazette  commented  on  his  work  that  highlighted  the  humanity  aspect  of  clinical  care  and  research  noted:  http://news.harvard.edu/gazette/story/2011/03/stuart-­‐t-­‐hauser/    

“His  passion  was  to  understand  the  construct  of  self-­‐identity  development—the  growing  capacity  of  the   individual   to   integrate   diverse   sources   of   information   (internal,   social   and   environmental),  balancing   the   needs   of   self   and   other,   to   move   forward   in   the   world.   As   much   as   Stuart   was  committed  to  understanding  the  development  of  the  individual  human  organism,  he  also  recognized  at  a  deep  level  the  profound  ways  in  which  family  interactions  shaped  this  development.  Not  content  with   the   paper   and   pencil   measures   available   at   the   time   to   assess   these   interactions,   Stuart  developed   methods   for   observing   family   interactions   in   vivo,   so   that   key   qualities   of   family  

relationships  could  be  better  understood  by  researchers.  Not  surprisingly,  a  favorite  adjective  of  his  applied   to   human   development  was   ‘complex’,   and   he   continually   sought   a   deeper   understanding  rather  than  simple,  facile  explanations.”    

 Another  pioneering  clinician  and  researcher   I  met  was  Prof.  Joseph  J.  Schildkraut.  An  article  commented  on  his  research  philosophy  (independent  thought,  rationality  and  objectivity)  that  reflects  current  approaches  in  contemporary  research:  http://news.harvard.edu/gazette/story/2008/10/joseph-­‐j-­‐schildkraut/    

“[In  1959],  having  selected  the  Massachusetts  Mental  Health  Center  because  of  its  reputation  as  a  program   offering   a   psychoanalytic   approach,   he   found   himself   as   a   trainee   intrigued   by   the  dramatic  response  of  depressed  patients  to  the  administration  of  electroconvulsive  therapy,  and  imipramine  and  phenelzine,  then  being  used  clinically  for  the  first  time.  Although  Joe  continued  to  be  respectful  of  psychoanalytic  treatments,  that  revelation  altered  his  academic  trajectory,  and  stoked   a   career   that   soon   played   a   major   role   in   launching   research   into   the   biological  mechanisms  of  depression.  The   result  of   this  work   [measuring  metabolites  of  norepinephrine]  was   a   paper,   “The   Catecholamine   Hypothesis   of   Affective   Disorders:   A   Review   of   Supporting  Evidence”   (1965).   This   paper   …   launched   25   years   of   global   research   on   the   relationship  between   neurotransmitter   function   and   affective   disorders   …   he   elaborated   the   concept  presented   in   his   seminal   review   article   by   defining   subtypes   of   depression   that   could   be  identified  by  their  biochemical  “signature”.  In  retrospect,  this  work  was  a  pioneering  precursor  of  current  research  that  seeks  to  replace  diagnoses  based  on  clinical  signs  and  symptoms  with  a  classification   scheme   grounded   in   biological   markers   that   are   much   closer   to   actual   disease  processes.   It   also   anticipated   current   efforts   toward   personalized   medicine,   to   identify  treatments  that  are  tailored  to  attack  disease  subtypes  defined  by  biological  markers,  including,  now,  allelic  variants  of  DNA.”  

 A  pioneer  in  behavioral  neuroscience  dear  to  my  heart  was  my  former  Ph.D.  advisor  Prof.  Bartley  G.  Hoebel  from   Princeton   University.   Bart   was   a   visionary   researcher   who   set   out   to   discover   the   brain   reward  circuitry.    His  enthusiasm  for  this  important  line  of  research  is  reflected  by  the  fact  that  he  truly  cared  for  the  wellbeing  of  his  students  and  the  society.  He  was  a  mentor  who  taught  cooperation  and  how  to  live  a  healthy  balanced  life.  His  friends  and  colleagues  commented:    http://www.princeton.edu/main/news/archive/S30/80/58G73/index.xml  http://www.examiner.com/article/food-­‐addiction-­‐expert-­‐bart-­‐hoebel-­‐leaves-­‐widely-­‐recognized-­‐legacy-­‐for-­‐future  

“His   interest   in   the  brain  mechanisms   that   control   appetite   and  body  weight  went   back   to  his  Harvard   days,   when   he   studied   under   renowned   behaviorist   B.F.   Skinner.   A   member   of   the  Princeton  faculty  since  1963,  [Bart’s]  interest  in  understanding  how  the  brain  rewards  behavior  encompassed  a  breadth  of   research  and   led   to  discoveries   in   the  areas  of  eating  disorders  and  obesity,   addiction,   alcohol   consumption   and   depression.   Some   of   his   earlier   research   included  examinations   of   how   animals   regulate   their   body   weight   and   the   neural   pathways   and  neurochemicals  involved  with  motivation.  A  1999  study  involved  examining  the  brain  chemistry  of   motivation   and   depression,   looking   at   how   dopamine   [and   acetylcholine]   reinforces  connections   between   cognitive   inputs   and   behavioral   output,   so   that   successful   behaviors   are  repeated.    “Bart’s  research  on  sugar  addiction  in  rats  generated  worldwide  attention  for  its  possible  public  health   applications.   His   work   allowed   scientists   to   examine   more   deeply   the   connections  between   food   cravings   and   brain   physiology,   with   the   hope   that   the   research   could   one   day  influence  work  related  to  humans  with  eating  disorders.    

‘[Bart]  was  a  pioneer  who  was  never  afraid  to  put  forth  a  new  idea  and  run  with  it  when  others  might  not  agree.  He  wanted  to  come  out  with  something  that  paved  the  way  for  new  areas  of  research.  Bart  was  very  creative  and  always  tried  to  come  up  with   original   ideas.   His   most   significant   research   unlocked   mysteries   about   how  neurotransmitters   send  messages  between   the  brain   and   the  body   to   turn  on   and  

shut  off  behaviors.  He  showed  that  sugar  addiction  causes  changes  in  the  brain  seen  with  drug  abuse  and  the  use  of  cocaine,  morphine,  and  nicotine.’    

Dr.   Sarah   Leibowitz   from   Rockefeller   University,   a   colleague  and  longtime  collaborator  with  Bart.    

 ‘Bart  always   loved  to  contribute.  His  science  on  diet  and  food  disorders  seemed  to  be  motivated  mainly  by  an  enthusiasm  for  helping  people,’  

Michael   Graziano,   associate   professor   of   psychology   at  Princeton.  

 “Beyond  his  research,  Hoebel  was  a  gracious  mentor  to  colleagues  and  students,  his  peers  said.  [Bart’s]  accomplishments  led  many  to  call  him  a  Rennaissance  man,  and  he  was  much  loved  for  his  sense  of  adventure  and  fun,  and  for  generously  sharing  his  time  and  knowledge.  He  followed  the  same  advice  he  gave  everyone:  'Do  what  you  love.'   'Lead  by  example.'  You  do  a  lot  more  by  doing  than  talking.’  

 ‘He  loved  teaching  and  was  dedicated  to  teaching  undergraduates  –  not  just  getting  up  there  and  lecturing  in  class,  but  training  young  people  to  be  scientists  and  really  caring  about  the  outcomes  of  their  lives.’  

Barry   Jacobs,   professor   of   psychology   and   the   Princeton  Neuroscience  Institute.  

 ‘Bart  was   the  very  best  example  of  a   friend,  professor  and  mentor.  He  was  always  the  most  generous  with  his  time,  ideas  and  support.  He  helped  many  of  his  students  achieve  great  things  but  also  to  find  a  balance  in  their  lives.’  

Mark   Gold,   chair   of   the   department   of   psychiatry   at   the  University  of  Florida.  

 Sadly,   Drs.   Hauser,   Schildkraut,   and  Hoebel   all   have   recently   passed   away.   They’ve   reminded  me   that  my  current  work  and  understanding  have  benefited  from  the  collective  efforts  of  early  pioneers  and  the  wisdom  that   they   passed   down   to   generations   of   students.   At   times,   I’ve   wondered  whether  my   encounters   with  these  three  individuals  came  from  my  desire  to  understand  the  brain  and  mind  from  their  points  of  view.    At  other  times,  I’ve  also  wondered  whether  I  was  placed  in  places  where  I  could  meet  these  individuals  to  learn  from   them.   In  either   case,   they   taught  me   three   fundamental  principles   that   I  needed   to  know   in  order   to  make  a  difference  in  someone’s  life.      Over   the   years,   I   became  more   aware   that  my  quest   to   understand   the  human  body,   brain   and  mind  was  really  about  discovering  what   it   is   to  be  a  human  being.  From   the  onset  of  my  career,   I  have  always  been  focused  on   applying  my   research   to   help   better   people’s  wellbeing   and   to   lessen   their   suffering   and  pain.  Over  time,  I  became  more  keenly  aware  that  “individual  wellbeing”  is  intimately  tied  to  “collective  wellbeing”  within  and  across  communities.  When  view  this  way,  I  clearly  see  that  working  toward  bettering  “collective  wellbeing”   is   an   important   endeavor.   Such   effort   requires   cooperation,  which   often   does   not   come   easily.  Nevertheless,  history  tells  us  that  successful  cooperation  is  not  totally  outside  the  realm  of  possibility,  even  during  difficulty  times.  In  the  spirit  of  an  ideal  from  one  very  special  person,  Dr.  John  Nash,  cooperation  can  occur   even   when   there   are   differences   in   goals   and   opinions.   Many   societal   issues,   such   as   joblessness,  poverty  and  improper  diet,  can  adversely  affect  brain-­‐body-­‐mind  health.  These  root  causes  can  be  resolved  if  individuals  and  communities  recognize  that  it  is  in  the  best  of  their  interests  to  focus  on  finding  solutions  for  improving  collective  wellbeing  as  well  as  the  wellbeing  of  individuals.  In  my  view,  Dr.  John  Nash’s  life  is  an  embodiment  of  this  ideal.  While  he  himself  faced  enormous  difficulties,  through  the  support  from  his  family,  friends  and  colleagues,  he  in  turn  was  able  to  make  a  difference  in  so  many  other  lives.            -­‐  David.  T.  Chau            June  19,  2015