PSYC 210 Chapter Notes - Chapter 9.2: Bipolar Disorder, Twin Study, Etiology
30 Apr 2018
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9.2$Etiology$of$Schizophrenia$
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Genetic'Factors!
Schizophrenia!has!a!large!genetic!component!
• Schizophrenia!is!genetically!heterogeneous!–!genetic!factors!may!vary!from!case!to!case!
o Mirrors!fact!that!schizophrenia!is!symptomatically!heterogeneous!
!!
Behavior!Genetics!Research!–!family,!twin,!and!adoption!studies!support!the!idea!that!genetic!factors!
play!a!role!in!schizophrenia!
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Family!studies!
• Show!that!genes'likely'play'a'role'in'schizophrenia!
• Relatives!of!people!with!schizophrenia!are!at!increased!risk!
o The!risk!increases!as!the!genetic!relationship!between!proband!and!relatives!becomes!closer!
• People!with!schizophrenia!in!their!family!histories!have!more!negative!symptoms!than!those!
families!free!of!schizophrenia!
o Findings!suggest!that!negative!symptoms!may!have!a!stronger!genetic!component!
• Incidence!of!schizophrenia!was!highest!for!children!who!had!two!admitted!parents!for!
schizophrenia!
o The!incidence!was!also!higher!for!people!with!one!parent!admitted!for!schizophrenia!and!
one!parent!admitted!for!bipolar!disorder!
o Findings!suggest!that!there!may!be!some!shared!genetic!vulnerability!between!
schizophrenia!and!bipolar!disorder!
• Influence!of!environment!cannot!be!discounted!in!explaining!the!higher!risks!among!relatives!
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Twin!studies!
• The!risk!for!identical/monozygotic!(MZ)!twins!is!44.3%!and!fraternal/dizygotic!twins!(DZ)!us!
12.08%!
o The'less-than-100-percent'concordance'in'MZ'twins'is'important:!
• If!genetic!transmission!alone!accounted!for!schizophrenia!and!one!identical!twin!had!
schizophrenia,!the!other!twin!would!also!have!schizophrenia!
• Suggest!that!negative!symptoms!may!have!a!stronger!genetic!component!than!do!positive!
symptoms!
• Common!shared!and!non-shared!environmental!factors!rather!than!common!genetic!factors!could!
account!for!some!portion!of!the!increased!risk!
• Analysis!of!the!high!risk!found!for!identical!twins!
o If!the!rates!of!schizophrenia!reflected!a!genetic!effect,!the!twins!without!schizophrenia!
would!presumably!carry!risk!genes!for!schizophrenia,!even!though!it!was!not!expressed!
behaviorally!
o Thus,!might!pass!along!increased!risk!for!the!disorder!to!their!children!
o Rate!of!schizophrenia!was!in!twins!without!schizophrenia!was!9.4%,!while!the!rate!among!
the!children!of!twins!with!schizophrenia!was!only!slightly!and!nonsignificantly!higher!at!
12.3%!
o Both!rates!are!substantially!higher!than!the!1%!prevalence!found!in!the!general!population!
• Further!supporting!the!importance!of!genetic!factors!in!schizophrenia!
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Adoption!studies!!
• Focus!on!the!study!of!children!whose!biological!mothers!had!schizophrenia!but!who!were!reared!
from!early!infancy!by!adoptive!parents!without!schizophrenia!
o Eliminate!the!possible!effects!of!being!reared!in!an!environment!where!a!parent!has!
schizophrenia!
• In!a!1966!study,!10.6%!of!the!offspring!of!women!with!schizophrenia!had!the!disorder!
• In!another!study,!the!risk!for!developing!schizophrenia!or!a!related!diagnosis!was!8.1%,!compared!
to!the!control!of!2.3%!
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Familial'high-risk'study:!a!study!involving!the!offspring!of!people!with!a!disorder,!such!as!schizophrenia,!!
who!have!a!high!probability!of!later!developing!a!disorder!
• High-risk'method:!a!research!technique!involving!the!intensive!examination!of!people,!such!as!the!
offspring!of!people!with!schizophrenia,!who!have!a!high!
• Study!begins!with!one!or!two!biological!parents!with!schizophrenia!and!follows!their!offspring!
longitudinally!to!identify…!
o How!many!of!these!children!may!develop!schizophrenia!
o What!types!of!childhood!neurobiological!and!behavioral!factors!may!predict!the!disorder's!
onset!
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Molecular!genetics!research!
• Understanding!what!constitutes!a!genetic!predisposition!for!schizophrenia!
• There!are!multiple!common!genes!associated!with!both!schizophrenia!and!bipolar!disorder!
o Try!to!narrow!in!on!specific!genes!by!establishing!how!often!specific!genes!and!a!particular!
trait!or!behavior!co-occur!
• DTNBP1!has!been!associated!with!schizophrenia!
o Codes!for!dysbindin!protein!expressed!throughout!the!brain!
o Protein!impacts!the!dopamine!and!glutamate!neurotransmitter!systems!
• Glutamate!+!proteins!promote!the!proper!placement!of!neurons!in!the!brain!during!
brain!development!
o Brains!of!people!with!schizophrenia!had!less!dysbindin!in!many!brain!areas,!including!the!
frontal!cortex,!temporal!cortex,!hippocampus,!and!limbic!system!structures!
• COMT!and!BDNF!have!been!associated!with!the!cognitive!deficits!associated!with!schizophrenia!
o COMT!is!associated!with!cognitive!control!processes!that!rely!on!the!prefrontal!cortex!
• Prefrontal'cortex:!the!region!of!the!frontal!lobe!of!the!brain!that!helps!maintain!an!
image!of!threats!and!rewards!faced,!as!well!as!maintain!focus!and!plan!relevant!to!
those!threats!and!rewards!
• Studies!have!shown!people!with!schizophrenia!have!deficits!in!cognitive!control!
processes,!including!planning,!working!memory,!and!problem!solving!
o BDNF!gene!has!been!linked!with!cognitive!function!in!people!with!and!without!
schizophrenia!
• Gene!has!a!polymorphism!Val66Met!where!Val!and!Met!are!two!alleles!and!a!person!
can!be!Val-Val,!Val-Met,!or!Met-Met!
• Verbal!memory!is!better!in!people!who!are!Val-Val!compared!to!Val-Met!or!Met-Met!
• These!genes!do!no!appear!in!genome-wide!association!studies!
o May!reflect!the!tremendous!genetic!heterogeneity!associated!with!schizophrenia!
• SNPs!associated!with!schizophrenia!are!also!associated!with!bipolar!disorder!
• Key!points!about!these!mutations:!
o They!are!all!very!rare!
o Only!a!small!number!of!people!with!these!rare!mutations!have!schizophrenia!
o They!are!not!specific!to!schizophrenia!
• People!with!the!same!disorder!may!not!necessarily!have!the!same!genetic!factors!contributing!to!
it!
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The'Role'of'Neurotransmitters!
Dopamine!theory!–!theory!that!schizophrenia!is!related!to!excess!activity!of!the!neurotransmitter!
dopamine!
• Based!on!the!knowledge!that!drugs!effective!in!treating!schizophrenia!reduce!dopamine!activity!
o Antipsychotic!drugs,!that!treat!some!symptoms!of!schizophrenia!by!blocking!B2!receptor,!
produce!side!effects!resembling!symptoms!of!Parkinson's!disease!
• Parkinson's!is!caused!in!part!by!low!levels!of!dopamine!in!a!particular!area!of!the!brain!
o Amphetamines,!which!amplify!dopamine!activity,!can!produce!a!state!that!closely!resembles!
schizophrenia!in!people!who!do!not!have!the!disorder!and!also!exacerbate!the!symptoms!of!
people!with!schizophrenia!
• This!assumption!is!too!simple!to!account!for!schizophrenia's!wide!range!of!symptoms!
• Dopamine!neurons!in!the!prefrontal!cortex!may!be!underactive!and!thus!fail!to!exert!inhibitory!
control!over!the!dopamine!neurons!in!subcortical!brain!areas,!like!the!amygdala!
o Results!in!dopamine!over-activity!
o Underactivity!of!the!dopamine!neurons!in!the!prefrontal!cortex!may!contribute!to!the!
negative!symptoms!of!schizophrenia!
• Brain!injury!to!prefrontal!cortex!
o -->!dopamine!neurons!under-active!in!prefrontal!cortex!!
• -->!negative!symptoms!
• -->!release!of!mesolimbic!dopamine!neurons!from!inhibitory!control!
§ -->!positive!symptoms!of!schizophrenia!
• Not!a!complete!theory!of!schizophrenia!
o Takes!several!weeks!for!antipsychotics!to!begin!lessening!the!positive!symptoms!of!
schizophrenia,!even!though!they!begin!blocking!receptors!rapidly!
• Disjunction!between!behavioral!and!pharmacological!effects!
• Possible!that!antipsychotics!block!D2!receptors,!but!the!change!in!positive!symptoms!
results!from!the!effect!this!blockade!has!on!other!brain!areas!and!neurotransmitter!
systems!
• Because!schizophrenia!is!a!disorder!with!widespread!symptoms!covering!perception,!emotion,!
cognition,!and!social!behavior,!it'is'unlikely'that'a'single'neurotransmitter'could'account'for'all'
symptoms!
!!
Other!neurotransmitters!
• Newer!drugs!partially!block!D2!receptors!and!also!serotonin!receptor!5HT2!
o Dopamine!neurons!generally!modulate!the!activity!of!other!neural!systems!
• In!the!prefrontal!cortex,!they!regulate!GABA!neurons!
• GABA!transmission!is!disrupted!in!the!prefrontal!cortex!of!people!with!schizophrenia!
o Serotonin!neurons!regulate!dopamine!neurons!in!the!mesolimbic!pathway!
• Low!levels!of!glutamate!have!been!found!in!the!cerebrospinal!fluid!of!people!with!schizophrenia!!
o Have!low!levels!of!the!enzyme!needed!to!make!glutamate!
o Cognitive!deficits!in!schizophrenia!by!the!prefrontal!cortex!and!symptom!disorganization!
may!be!connected!to!deficits!with!NMDA!
Document Summary
Schizophrenia is genetically heterogeneous genetic factors may vary from case to case: mirrors fact that schizophrenia is symptomatically heterogeneous. Behavior genetics research family, twin, and adoption studies support the idea that genetic factors play a role in schizophrenia. Influence of environment cannot be discounted in explaining the higher risks among relatives. The risk for identical/monozygotic (mz) twins is 44. 3% and fraternal/dizygotic twins (dz) us. 12. 08: the less-than-100-percent concordance in mz twins is important: If genetic transmission alone accounted for schizophrenia and one identical twin had schizophrenia, the other twin would also have schizophrenia. 12. 3: both rates are substantially higher than the 1% prevalence found in the general population. Further supporting the importance of genetic factors in schizophrenia. Focus on the study of children whose biological mothers had schizophrenia but who were reared from early infancy by adoptive parents without schizophrenia: eliminate the possible effects of being reared in an environment where a parent has schizophrenia.
