RT Book, Section
A1 Sklar, Pamela
A2 Murray, Michael F.
A2 Babyatsky, Mark W.
A2 Giovanni, Monica A.
A2 Alkuraya, Fowzan S.
A2 Stewart, Douglas R.
SR Print(0)
ID 1102705677
T1 Schizophrenia
T2 Clinical Genomics: Practical Applications in Adult Patient Care
YR 2014
FD 2014
PB McGraw-Hill Education
PP New York, NY
SN 9780071622448
LK accessbiomedicalscience.mhmedical.com/content.aspx?aid=1102705677
RD 2024/04/19
AB Disease  summary:Schizophrenia  (SCZ)  is  a  severe,  chronic  psychiatric  syndrome  that  is  a  complex  genetic  disorder  involving  the  interactions  of  multiple  genetic  and  nongenetic  factors.Clinical  diagnosis  is  based  on  abnormalities  in  multiple  domains  including  positive  symptom  domain,  negative  symptoms,  cognition,  and  mood  symptoms.  No  blood  or  neuroimaging  tests  are  pathognomic.Presentation  is  generally  in  adolescence  or  early  adulthood  but  a  premorbid  prodrome  is  often  apparent  earlier  suggesting  a  neurodevelopmental  trajectory.The  course  is  most  often  chronic  with  significant  impairments  in  social  and  work  functioning.Neuroimaging  finds  decreased  activation  in  task-induced  magnetic  resonance  imaging  (MRI)  paradigms  in  several  brain  regions  including  the  dorsolateral  prefrontal  cortex  and  anterior  cingulate.  Diffusion  tensor  imaging  has  also  identified  white  matter  tract  abnormalities.Differential  diagnosis:Major  differential  is  with  other  psychotic  disorders  (bipolar  disorder  [BD],  schizoaffective  disorder,  delusional  disorder,  and  depression  with  psychotic  features).  Other  significant  differential  includes  (1)  psychotic  disorder  due  to  medical  conditions  (eg,  epilepsy,  dementia,  brain  tumor,  infections,  and  metabolic  abnormalities),  (2)  substance  use  (eg,  drugs  of  abuse,  medications,  toxins),  and  (3)  brief  or  SCZ  spectrum  syndromes.Monogenic  forms:There  are  no  agreed  upon  monogenic  forms,  no  single  gene  has  been  demonstrated  to  cause  SCZ.Family  history:Strongest  risk  for  SCZ  is  a  positive  family  history.  Affected  first-degree  relatives  confer  a  relative  risk  of  5%  to  16%.  A  recent  large-scale  study  shows  that  first-degree  relatives  are  also  at  increased  risk  of  BD  (3.7%).Twin  studies:Monozygotic  twins  have  0.9  concordance  rate,  dizygotic  twins  have  0.5,  with  an  estimated  heritability  of  approximately  0.8.Nonfamilial  genetics:  Advanced  paternal  age  is  associated  with  elevated  relative  risk  (two-  to  threefold).  De  novo  single-nucleotide  polymorphism  (SNP)  and  copy-number  variants  (CNV)  rates  are  increased  in  SCZ.Environmental  factors:Multiple  environmental  factors  have  been  associated  with  modest  increased  risk  including  obstetrical  complications,  prenatal  infections,  socioeconomic  status,  immigration  status,  urban  living,  maternal  starvation,  head  injury,  and  cannabis  use.Genome-wide  associations:Significant  genome-wide  associations  exist  for  both  CNVs  and  SNPs.  Large  CNVs  are  associated  with  larger  risk,  but  produce  pleiotropic  phenotypes  (ie,  not  specific  for  SCZ).  Testing  for  CNVs  or  SNPs  is  not  yet  clinically  validated  for  diagnosis  or  treatment  selection.Pharmacogenomics:Most  antipsychotic  medication  is  metabolized  by  the  cytochrome  P450  (CYP)  system.  Clinical  efficacy  of  CYP  testing  has  not  been  established.