PMID- 17434919
OWN - NLM
STAT- MEDLINE
DCOM- 20071226
LR  - 20070829
IS  - 1047-3211 (Print)
IS  - 1047-3211 (Linking)
VI  - 17 Suppl 1
DP  - 2007 Sep
TI  - Catecholamine and second messenger influences on prefrontal cortical networks of 
      "representational knowledge": a rational bridge between genetics and the symptoms 
      of mental illness.
PG  - i6-15
AB  - Both dopamine (DA) and norepinephrine (NE) have powerful, inverted U influences 
      on prefrontal cortical (PFC) cognitive function. Optimal NE levels engage 
      alpha2A-adrenoceptors and increase "signals" via inhibition of cAMP-HCN 
      (cAMP-hyperpolarization-activated cyclic nucleotide-gated cation channel) 
      signaling near preferred inputs, whereas optimal levels of DA D1 receptor 
      stimulation decrease "noise" by increasing cAMP signaling near nonpreferred 
      inputs. Excessive levels of catecholamine release during stress impair working 
      memory 1) by very high levels of cAMP-HCN signaling diminishing preferred as well 
      as nonpreferred inputs and 2) by high levels of NE engaging alpha1 stimulation of 
      phosphotidyl inositol (PI) signaling that suppresses cell firing. Common mental 
      illnesses are associated with extracellular changes in these pathways: Attention 
      Deficit Hyperactivity Disorder is linked to genetic changes that reduce 
      catecholamine transmission to suboptimal levels and is treated with agents that 
      increase catecholamine transmission, whereas Post-Traumatic Stress Disorder 
      (PTSD) is associated with amplified noradrenergic transmission that impairs PFC 
      but strengthens amygdala function. PTSD is now treated with agents that block 
      alpha1 or beta adrenoceptors. In contrast, the more severe mental illnesses, 
      schizophrenia and bipolar disorder, are associated with genetic changes in 
      molecules regulating intracellular signaling pathways activated by stress. 
      Specifically, DISC1 inhibits cAMP signaling whereas regulator of G-protein 
      signaling 4 inhibits PI signaling. Loss of function in these genes may render 
      patients vulnerable to profound stress-induced PFC dysfunction including symptoms 
      of thought disorder.
FAU - Arnsten, Amy F T
AU  - Arnsten AF
AD  - Department of Neurobiology, Kavli Institute of Neuroscience, Yale Medical School, 
      New Haven, CT 06510, USA. amy.arnsten@yale.edu
LA  - eng
GR  - P50 MH068789/MH/NIMH NIH HHS/United States
GR  - R37 AG06036/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20070413
PL  - United States
TA  - Cereb Cortex
JT  - Cerebral cortex (New York, N.Y. : 1991)
JID - 9110718
RN  - 0 (Catecholamines)
SB  - IM
MH  - Animals
MH  - Arousal/physiology
MH  - Catecholamines/*genetics/*physiology
MH  - Dendrites/physiology
MH  - Extracellular Space/metabolism
MH  - Humans
MH  - Mental Disorders/*genetics/*physiopathology
MH  - Nerve Net/*physiology
MH  - Prefrontal Cortex/*physiology
MH  - Second Messenger Systems/*genetics/*physiology
MH  - Stress, Psychological/physiopathology/psychology
RF  - 101
EDAT- 2007/04/17 09:00
MHDA- 2007/12/27 09:00
CRDT- 2007/04/17 09:00
PHST- 2007/04/17 09:00 [pubmed]
PHST- 2007/12/27 09:00 [medline]
PHST- 2007/04/17 09:00 [entrez]
AID - bhm033 [pii]
AID - 10.1093/cercor/bhm033 [doi]
PST - ppublish
SO  - Cereb Cortex. 2007 Sep;17 Suppl 1:i6-15. doi: 10.1093/cercor/bhm033. Epub 2007 
      Apr 13.