Neuroscience in the 21st Century: From Basic to Clinical

4109 Pages·2016·121.95 MB·English

by  Donald W. Pfaff

Donald W. Pfaff
Nora D. Volkow
Editors-in-Chief
Neuroscience
in the
21st Century
From Basic to Clinical
Second Edition
Neuroscience in the 21st Century
(cid:129)
Donald W. Pfaff Nora D. Volkow
Editors-in-Chief
Neuroscience in the
21st Century
From Basic to Clinical
Second Edition
With1294Figuresand107Tables
Editors-in-Chief
DonaldW.Pfaff NoraD.Volkow
LaboratoryofNeurobiologyandBehavior NationalInstituteonDrugAbuse(NIDA)
TheRockefellerUniversity NationalInstitutesofHealth(NIH)
NewYork,NY,USA Rockville,MD,USA
ISBN978-1-4939-3473-7 ISBN978-1-4939-3474-4(eBook)
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DOI10.1007/978-1-4939-3474-4
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Preface to the Second Edition
Theprimarypurposeofthisprojecthasbeentoproduceacomprehensive,electronic
introduction to current-day neuroscience in a didactic form useful for upper-level
premedical students, entering medical students, and graduate students in a wide
variety of countries, with an emphasis on economically developing countries. The
Supervisory Editors and the authors, in their international distribution, reflect our
intentiontorecognizethegrowinginterestinneuroscienceandexpertiseacrossthe
world.
Neuroscience Addresses Medical and Public Health Problems,
Worldwide
Neuroscience research provides basic discoveries about how the brain works and
how it controls behavior and how its disruption can result in neurological and
psychiatric disorders. These discoveries are of relevance for improving multiple
outcomes that span from health (i.e., how to maximize cognitive performance and
optimizewellbeing)toeducation(i.e.,howtouseknowledgefromneuroscienceon
how the brain learns to improve the delivery of education). Neuroscience broadly
definedalsoofferspivotalcomponentsofbothmedicaleducationandthedeliveryof
medical services. For example, depression and schizophrenia – once viewed as
purely “behavioral” problems – are now candidates for neurochemical/neurophar-
macologicaltreatments.Similarlyaddiction,whichwasonceviewedasacondition
of moral weakness, is now recognized as a disease of the brain with impairment
in specific brain circuits. Degenerative conditions such as neurosyphilis,
HIV-associateddementia,traumaticbraininjury,andAlzheimercannowbedelayed
byscience-basedtreatments.Comaandpersistentvegetativestateareapproachedby
manipulating brain mechanisms responsible for arousal. Indeed, as neuroscience
explores the etiology of disease – the complex interplay between biological, psy-
chological,andsocioculturalfactors–itisincreasinglyvaluableinunderstandingan
arrayofdiseases.ArecentreportbytheSurgeonGeneral,intheUSA,citesseveral
suchdiseases:schizophrenia,bipolardisorder,earlyonsetdepression,autism,atten-
tion deficit/hyperactivity disorder, anorexia nervosa, substance use disorders, and
panicdisorder,amongmanyothers.
v
vi PrefacetotheSecondEdition
TheSurgeonGeneralstatesthatintheUSA,the1-yearprevalencerateformental
illness is about 21 %. The figure was derived by synthesizing two major studies
indicating that within a 1-year period this percentage of the adult population has a
diagnosablementaldisorderbasedon“reliable,establishedcriteria.”Basedon2010
census figures, this means that over 45 million individuals are affected. Moreover,
theSurgeonGeneralindicatesthatalmosthalftheseindividuals–9 %ofUSadults–
experience some significant functional impairment. A subpopulation of 5.4 % of
adults has a “serious” mental illness that interferes with some area of social
functioning.
Most distressingly, none of these huge figures included even the approximately
20 % of children and adolescents estimated to have mental disorders with at least
mild functional impairment, or the 5–9 % who suffer “serious emotional distur-
bance.” Adults 55 and older are another subpopulation. Though not as extensively
documented, the Surgeon General cites figures indicating that almost 20 % have
somediagnosablementaldisorderduringa1-yearperiod,andthatalmost4 %havea
seriousmentalillness.
Various reports from the World Health Organization (WHO) demonstrate that
mental health problems in the USA are mirrored in other countries, often in an
extremeformbecausethereislesshelpavailable.Herearesomeofthefindings:
(cid:129) Mental, neurological, and behavioral disorders are common to all countries and
causeimmensesuffering.Peoplewiththesedisordersareoftensubjectedtosocial
isolation, poor quality of life, and increased mortality. These disorders are the
causeofstaggeringeconomicandsocialcosts.Thatis,becausementaldisorders
oftenstrikeearly,theirtotaleconomiccosttosocietyisalmostaslargeasallother
illnessescombined.
(cid:129) Hundreds of millions of people worldwide are affected by mental, behavioral,
neurological,andsubstanceusedisorders.Forexample,estimatesmadebyWHO
in 2002 showed that 154 million people globally suffer from depression and
25millionpeoplefromschizophrenia;91millionpeopleareaffectedbyalcohol
use disorders and 15 million by drug use disorders. A recently published WHO
report shows that 50 million people suffer from epilepsy and 24 million from
Alzheimerandotherdementias.
(cid:129) Inadditiontotheabovefigures,manyotherdisordersaffectthenervoussystemor
produce neurological sequelae. Projections based on a WHO study show that
worldwidein2005,326millionpeoplesufferedfrommigraine;61millionfrom
cerebrovascular diseases; 18 million from nervous system infections or neuro-
logicalsequelaeofinfections.Thenumberofpeoplewithneurologicalsequelae
ofnutritionaldisordersandneuropathies(352million)andneurologicalsequelae
secondary to injuries (170 million) also add substantially to the above burden.
Uncounted are the large number of people who suffer from chronic pain. In the
USA alone it is estimated that at least 100 million Americans suffer from a
chronicpaincondition.
(cid:129) About 877,000 people die by suicide every year. In at least two thirds of these
cases,atreatablementalillnessisdeemedtobecausal.
PrefacetotheSecondEdition vii
(cid:129) Oneinfourpatientsvisitingahealthservicehasatleastonemental,neurological,
or behavioral disorder, but most of these disorders are neither diagnosed nor
treated.
(cid:129) Mental illnesses affect and are affected by chronic conditions such as cancer,
heartandcardiovasculardiseases,diabetes,andHIV/AIDS.Untreated,theybring
about unhealthy behavior, noncompliance with prescribed medical regimens,
diminished immune functioning, and poor prognosis. Some common disorders,
such as lung cancer, are the consequence of mental disorders (in this case,
nicotineaddiction).
(cid:129) Cost-effectivetreatmentsexistformostdisordersand,ifcorrectlyapplied,could
enablemostofthoseaffectedtobecomefunctioningmembersofsociety.
(cid:129) Barriers to effective treatment of mental illness and substance use disorders
include lack of recognition of the seriousness of mental illness and lack of
understanding about the benefits of services. Policy makers, insurance compa-
nies,healthandlaborpolicies,andthepublicatlarge–alldiscriminatebetween
physicalandmentalproblems.
(cid:129) Most middle- and low-income countries devote less than 1 % of their health
expenditure to mental health. There are as many as 200 times more psychiatric
workers in high-income as opposed to low-income countries. Consequently
mental and behavioral health policies, legislation, community care facilities,
and treatments for people with mental illness are not given the priority they
deserve.
(cid:129) Warandotherdisastershaveamajorinfluenceonmentalhealthandpsychosocial
well-being.Ratesofmentalhealthdisordertendtodoubleafteremergencies.
Early support for the ideas underlying this project came through letters
expressing clear understanding and encouragement from the Society for Neuro-
science(thePresidentandtheChairoftheEducationCommittee),theFederation
ofEuropeanNeuroscienceSocieties(FENS),theJapaneseNeuroscienceSociety,
the Indian Academy of Neuroscience, from UNESCO, from the International
Brain Research Organization (IBRO, whose regional offices will assist with
dissemination of the text), from the Director of the Earth Institute, Jeffrey
D. Sachs (Professor of Sustainable Development, Columbia University), from
the American expert on education Professor Howard Gardner (Harvard Univer-
sity),andfromtheChineseAcademyofSciences(threemembersareamongour
editors).
Insofarasprofessorsindevelopingcountrieswanttousethistextaspartoftheir
efforts to launch neuroscience programs, they might want to see the Appendix by
Richard Brown (Dalhousie University, Canada), a paper that gives tips about
developing such programs. In addition, a few authors have supplied videos to let
students in developing countries know how these authors became interested in
neuroscienceandtogiveanideaofwhattheirlaboratorieslooklike.
Finally,weconsiderthislargevolumetocomprisea“feedertext”forother,more
detailedtreatmentssuchasthoseeditedbyEricKandeletal.(PrinciplesofNeural
Science,5thedition,McGraw-Hill),LarrySquireetal.(FundamentalNeuroscience,
viii PrefacetotheSecondEdition
3rdedition,Elsevier),andDalePurvesetal.(Neuroscience,4thedition,Sinauer).At
spotsinthecurrenttext,wehavereferredtospecificchaptersinoneormoreofthese
textsinordertomakeupforanypotentialdeficit.
We gratefully acknowledge financial support for the first edition from three
foundations: the Nour, Moos, and New York NeuroScience Foundations and from
Pfizer, Inc. All authors and editors agreed to do their work without compensation.
This entire project benefitted from the wise counsel and foresight of the Neurosci-
enceeditoratSpringer,AnnAvouris.Withahighlevelofskill,Annhasencouraged
and guided this project from its inception to its completion. Special thanks to the
International Brain Research Organization (Pierre Magistretti and Sten Grillner,
Secretary-Generals) for assisting the free international distribution of this text, in
electronicform,touniversitiesindevelopingcountries.
NewYork,NY,USA DonaldW.Pfaff
Rockville,MD,USA NoraD.Volkow
Preface to the First Edition
Theprimarypurposeofthisprojecthasbeentoproduceacomprehensive,electronic
introduction to current-day neuroscience in a didactic form useful for upper level
premedical students, entering medical students, and graduate students in a wide
varietyofcountries.TheSupervisory Editors andtheauthors,intheirinternational
distribution, reflect our intention to recognize the growing interest in neuroscience
andexpertiseinneuroscientificresearchacrosstheworld.
Neuroscience Addresses Medical and Public Health Problems
Worldwide
Neuroscience research provides basic discoveries about how the brain works and
about how the brain controls behavior. These discoveries are then applied for the
goodofhumankind.Neuroscience,broadlydefined,alsoofferspivotalcomponentsof
bothmedicaleducationandthedeliveryofmedicalservices.Forexample,depression
and schizophrenia – onceviewedaspurely“behavioral” problems– are now candi-
dates for neurochemical/neuropharmacological treatments. Degenerative conditions
suchasneurosyphilis,HIV-associateddementia,andAlzheimer’scannowbedelayed
byscience-basedtreatments.Comaandpersistentvegetativestateareapproachedby
manipulating brain mechanisms responsible for arousal. Indeed, as neuroscience
explorestheetiologyofdisease–thecomplexinterplaybetweenbiological,psycho-
logical,andsocioculturalfactors–itisincreasinglyvaluableinunderstandinganarray
ofdiseases.ArecentreportbytheSurgeonGeneral,intheUnitedStates,citesseveral
such diseases: schizophrenia, bipolar disorder, early onset depression, autism, atten-
tion deficit/hyperactivity disorder, anorexia nervosa, substance abuse disorders, and
panicdisorder,amongmanyothers.
TheSurgeonGeneralstatesthatintheUSA,the1-yearprevalencerateformental
illness is about 21 %. The figure was derived by synthesizing two major studies
indicating that within a 1-year period this percentage of the adult population has a
diagnosable mental disorder based on “reliable, established criteria.” Based on
2010 census figures, this means that over 45 million individuals are affected.
Moreover, the Surgeon General indicates that almost half these individuals – 9 %
ofUSadults–experiencesomesignificantfunctionalimpairment.Asubpopulation
ix
x PrefacetotheFirstEdition
of5.4 %ofadults havea“serious”mentalillness thatinterfereswithsomearea of
socialfunctioning.
Most distressingly, none of these huge figures even included the approximately
20 % of children and adolescents estimated to have mental disorders with at least
mild functional impairment, or the 5–9 % who suffer “serious emotional distur-
bance.” Adults aged 55 years and older are another subpopulation. Though not as
extensively documented, the Surgeon General cites figures indicating that almost
20 %havesomediagnosablementaldisorderduringa1-yearperiodandthatalmost
4 %haveaseriousmentalillness.
Various reports from the World Health Organization (WHO) demonstrate that
mental health problems in the USA are mirrored in other countries, often in an
extremeformbecausethereislesshelpavailable.Herearesomeofthefindings:
(cid:129) Mental, neurological, and behavioral disorders are common to all countries and
causeimmensesuffering.Peoplewiththesedisordersareoftensubjectedtosocial
isolation, poor quality of life, and increased mortality. These disorders are the
causeofstaggeringeconomicandsocialcosts.Thatis,becausementaldisorders
oftenstrikeearly,theirtotaleconomiccosttosocietyisalmostaslargeasallother
illnessescombined.
(cid:129) Hundreds of millions of people worldwide are affected by mental, behavioral,
neurological, and substance abuse disorders. For example, estimates made by
WHO in 2002 showed that 154 million people globally suffer from depression
and 25 million people from schizophrenia; 91 million people are affected by
alcohol abuse disorders and 15 million by drug abuse disorders. A recently
published WHO report shows that 50 million people suffer from epilepsy and
24millionfromAlzheimerandotherdementias.
(cid:129) Inadditiontotheabovefigures,manyotherdisordersaffectthenervoussystemor
produce neurological sequelae. Projections based on a WHO study show that
worldwidein2005,326millionpeoplesufferedfrommigraine,61millionfrom
cerebrovascular diseases, and 18 million from nervous system infections or
neurological sequelae of infections. The number of people with neurological
sequelaeofnutritionaldisordersandneuropathies(352million)andneurological
sequelae secondary to injuries (170 million) also add substantially to the above
burden.Uncountedarethelargenumberofpeoplewhosufferfromchronicpain.
(cid:129) About877,000peopledieeveryyearbycommittingsuicide.Inatleasttwothirds
ofthesecases,atreatablementalillnessisdeemedtobecausal.
(cid:129) Oneinfourpatientsvisitingahealthservicehasatleastonemental,neurological,
or behavioral disorder, but most of these disorders are neither diagnosed nor
treated.
(cid:129) Mental illnesses affect and are affected by chronic conditions such as cancer,
heart, and cardiovascular diseases; diabetes, and HIV/AIDS. Untreated, they
bring about unhealthy behavior, noncompliance with prescribed medical regi-
mens, diminished immune functioning, and poor prognosis. Some common
disorders,suchaslungcancer,aretheconsequencesofmentaldisorders(inthis
case,nicotineaddiction).