Endophenotypes in bipolar disorder

Lenox, Robert H.; Gould, Todd D.; Manji, Husseini K.

doi:10.1002/ajmg.10360

Cited by 264Bipolar Disorder and TreatmentSchizophrenia research and treatmentCircadian rhythm and melatonin

Endophenotypes in bipolar disorder

Lenox, Robert H., Gould, Todd D., Manji, Husseini K.·2002·American Journal of Medical Genetics

DOI 10.1002/ajmg.10360

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Abstract

The search for genes in bipolar disorder has provided numerous genetic loci that have been linked to susceptibility to developing the disorder. However, because of the genetic heterogeneity inherent in bipolar disorder, additional strategies may need to be employed to fully dissect the genetic underpinnings. One such strategy involves reducing complex behaviors into their component parts (endophenotypes). Abnormal neurophysiological, biochemical, endocrinological, neuroanatomical, cognitive, and neuropsychological findings are characteristics that often accompany psychiatric illness. It is possible that some of these may eventually be useful in subdefining complex genetic disorders, allowing for improvements in diagnostic assessment, genetic linkage studies, and development of animal models. Findings in patients with bipolar disorder that may eventually be useful as endophenotypes include abnormal regulation of circadian rhythms (the sleep/wake cycle, hormonal rhythms, etc.), response to sleep deprivation, P300 event-related potentials, behavioral responses to psychostimulants and other medications, response to cholinergics, increase in white matter hyperintensities (WHIs), and biochemical observations in peripheral mononuclear cells. Targeting circadian rhythm abnormalities may be a particularly useful strategy because circadian cycles appear to be an inherent evolutionarily conserved function in all organisms and have been implicated in the pathophysiology of bipolar disorder. Furthermore, lithium has been shown to regulate circadian cycles in diverse species, including humans, possibly through inhibition of glycogen synthase kinase 3-beta (GSK-3beta), a known target of lithium.

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Major hallmarks of major depressive disorder and bipolar disorder include abnormal sleep/wake, appetite, and social rhythms.
“Indeed some of the major hallmarks of diseases like major depressive disorder (MDD) and bipolar disorder (BPD) are abnormal sleep/wake, appetite, and social rhythms (Boivin, 2000; Bunney and Bunney, 2000; Lenox et al., 2002; Grandin et al., 2006).”
From Circadian genes, rhythms and the biology of mood disorders (2007) · cites this paper as Lenox et al., 2002

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Authors: Lenox, R. H., Gould, T. D., & Manji, H. K.
Affiliations: University of Pennsylvania (US)
National Institutes of Health (US)
Corresponding author: Manji, Husseini K.
ORCID: Gould, Todd D.
Manji, Husseini K.
Venue: American Journal of Medical Genetics
Publisher: Wiley
Published: 2002-05-08
Volume: 114
Issue: 4
Pages: 391-406
ISSN: 0148-7299 (ISSN-L)
1096-8628
DOI: 10.1002/ajmg.10360
OpenAlex: W2078774097
Cited by: 264
References: 244
Citations by year: 2024: 2 · 2022: 6 · 2021: 2 · 2020: 3 · 2019: 5 · 2018: 4 · 2017: 5 · 2016: 5 · 2015: 4 · 2014: 9 · 2013: 13 · 2012: 15
FWCI: 3.68
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: American Journal of Medical Genetics (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01mh059959-03)
National Center for Research Resources (RR01 MH59959)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
Keywords: bipolar disorder, endophenotypes, circadian rhythm disruption, sleep-wake cycle, P300 event-related potential, cholinergic response, white matter hyperintensities, peripheral blood mononuclear cells, lithium, glycogen synthase kinase-3β, genetic susceptibility, genetic heterogeneity, animal models
MeSH terms: Central Nervous System Stimulants, Animals, Bipolar Disorder, Circadian Rhythm, Humans, Leukocytes, Mononuclear, Lithium, Phenotype, Sleep Deprivation, Signal Transduction, Calcium-Calmodulin-Dependent Protein Kinases, Event-Related Potentials, P300, Genetic Predisposition to Disease, Glycogen Synthase Kinases, Glycogen Synthase Kinase 3

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Endophenotypes in bipolar disorder

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