Journal
CEREBRAL CORTEX
Volume 17, Issue -, Pages I6-I15Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhm033
Keywords
ADHD; bipolar; dopamine; norepinephrine; PTSD; schizophrenia; working memory
Categories
Funding
- NIA NIH HHS [R37 AG06036] Funding Source: Medline
- NIMH NIH HHS [P50 MH068789] Funding Source: Medline
Ask authors/readers for more resources
Both dopamine (DA) and norepinephrine (NE) have powerful, inverted U influences on prefrontal cortical (PFC) cognitive function. Optimal NE levels engage alpha 2A-adrenoceptors and increase signals via inhibition of cAMP-HCN (cAMP-hyperpolarizationactivated 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 all 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 alpha 1 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available