Document Detail

Toward a biaxial model of "bipolar" affective disorders: spectrum phenotypes as the products of neuroelectrical and neurochemical alterations.
MedLine Citation:
PMID:  16725206     Owner:  NLM     Status:  MEDLINE    
Based upon a synthesis of findings related to affective illness, a pathophysiologic hypothesis and possible nosology are proposed. The authors reviewed recent (2001-2004) phenomenologic, diagnostic and treatment literature for pathophysiologic implications and selectively reviewed genetic, neuroimaging, neurochemical and neuropathological studies (1966-2004) that might inform the hypothesized model. Modern DSM nosology of affective illness is based upon the accumulation of observations in the purely descriptive tradition and has little pathophysiologic basis. A new perspective, that of the bipolar spectrum, deriving from clinical, theoretical and epidemiologic considerations, appears more promising for building bridges with the emerging neurobiology of bipolar disorder. Research seeking associations between structural alterations (molecular, cellular and system-level) and behavioral-level pathophysiologic processes has provided many clues, but no population-wide, major genetic loci have been identified. Three general hypotheses have emerged in the literature implicating: 1) presynaptic electrical signaling, an early suggestion which has received less recent consideration, 2) neurotransmitter-receptor systems (first messenger) and 3) post-receptor neurochemical signaling systems (second-- and third messenger). The current 'biaxial' hypothesis proposes: 1) affective regulation may be understood in terms of two primary functional spectra: mood range and mood tonicity, 2) these spectra, in turn, are determined by neurochemical capacity and neuroelectrical modulation-and their functional interaction, and 3) proposed cellular pathophysiology suggests primary molecular loci, that may predict phenomenologic patterns and treatment responsiveness.
Kathleen Askland; Margaret Parsons
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Publication Detail:
Type:  Journal Article; Review     Date:  2006-05-24
Journal Detail:
Title:  Journal of affective disorders     Volume:  94     ISSN:  0165-0327     ISO Abbreviation:  J Affect Disord     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-07-28     Completed Date:  2007-01-09     Revised Date:  2009-09-28    
Medline Journal Info:
Nlm Unique ID:  7906073     Medline TA:  J Affect Disord     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  15-33     Citation Subset:  IM    
Dartmouth-Hitchcock Medical Center, Dartmouth Medical School, Hanover, NH 03755, United States.
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MeSH Terms
Anticonvulsants / therapeutic use
Bipolar Disorder / diagnosis*,  drug therapy,  genetics,  physiopathology*
Brain / drug effects,  physiopathology
Diagnosis, Differential
Diagnostic and Statistical Manual of Mental Disorders
Ion Channels / drug effects,  genetics,  physiology
Models, Neurological*
Neurotransmitter Agents / physiology
Presynaptic Terminals / drug effects,  physiology
Receptors, Neurotransmitter / drug effects,  genetics,  physiology
Signal Transduction / drug effects,  genetics,  physiology
Sodium-Potassium-Exchanging ATPase / genetics,  physiology
Reg. No./Substance:
0/Anticonvulsants; 0/Ion Channels; 0/Neurotransmitter Agents; 0/Receptors, Neurotransmitter; EC ATPase

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