Twin study of the 24-h cortisol profile: evidence for genetic control of the human circadian clock

Linkowski, Paul; Onderbergen, Anne Van; Kerkhofs, Myriam; Bosson, Danièle; Mendlewicz, Julien; Cauter, Eve Van

doi:10.1152/ajpendo.1993.264.2.e173

Cited by 106 publications

(101 citation statements)

References 2 publications

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“…There is strong evidence for a genetic control of the human circadian clock (Linkowski et al, 1993), and a familial variant of human sleep behavior has been attributed to a mutation in a human clock gene (Toh et al, 2001). The influence of a functional polymorphism within the angiotensin I-converting enzyme (ACE) gene on partial sleep deprivation in patients with MDD is probably mediated by dopaminergic neurotransmission (Baghai et al, 2003).…”

Section: Diurnal Variationmentioning

confidence: 99%

Discovering Endophenotypes for Major Depression

Hasler

Drevets

Manji

et al. 2004

Neuropsychopharmacol

1,022

739

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The limited success of genetic studies of major depression has raised questions concerning the definition of genetically relevant phenotypes. This paper presents strategies to improve the phenotypic definition of major depression by proposing endophenotypes at two levels: First, dissecting the depressive phenotype into key components results in narrow definitions of putative psychopathological endophenotypes: mood bias toward negative emotions, impaired reward function, impaired learning and memory, neurovegetative signs, impaired diurnal variation, impaired executive cognitive function, psychomotor change, and increased stress sensitivity. A review of the recent literature on neurobiological and genetic findings associated with these components is given. Second, the most consistent heritable biological markers of major depression are proposed as biological endophenotypes for genetic studies: REM sleep abnormalities, functional and structural brain abnormalities, dysfunctions in serotonergic, catecholaminergic, hypothalamic-pituitary-adrenocortical axis, and CRH systems, and intracellular signal transduction endophenotypes. The associations among the psychopathological and biological endophenotypes are discussed with respect to specificity, temporal stability, heritability, familiality, and clinical and biological plausibility. Finally, the case is made for the development of a new classification system in order to reduce the heterogeneity of depression representing a major impediment to elucidating the genetic and neurobiological basis of this common, severe, and often life-threatening illness.

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Section: Diurnal Variationmentioning

confidence: 99%

Discovering Endophenotypes for Major Depression

Hasler

Drevets

Manji

et al. 2004

Neuropsychopharmacol

1,022

739

View full text Add to dashboard Cite

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“…To our knowledge, in mammals between individual glucocorticoid repeatability has not been investigated so far. There is however evidence for some genetic predisposition of glucocorticoid excretion mechanisms (Linkowski et al, 1993;Oswald et al, 2004;Pflüger et al, 2016). Furthermore, a multitude of species has prolonged phases of intensive maternal care (e.g., Purvis and Harvey, 1995), rendering priming of glucocorticoid excretion patterns possible (e.g., Plotsky and Meaney, 1993, but see Aizer et al, 2015;Berghänel et al, 2016;Murray et al, 2016;McCormick et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Circadian Rhythms of Urinary Cortisol Levels Vary Between Individuals in Wild Male Chimpanzees: A Reaction Norm Approach

et al. 2018

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Investigating the repeatability of trait variation between individuals, that is the amount of individual variation in relation to overall phenotypic variation, indicates an upper level of heritability and reveals whether a given trait may be subject to selection. Labile traits are characterized by high levels of flexibility and consequently low trait repeatability is expected. Indeed, research examining glucocorticoid levels in various non-mammal species found low repeatability scores. However, mammals may be different in this respect as (i) differential maternal care early in life has the potential to prime hypothalamic-pituitary-adrenal axis functioning and (ii) allelic variation affecting hypothalamic-pituitary-adrenal axis functioning has been reported. Individuals often differ from each other in average and/or plastic labile trait expression, two aspects that can be described using a reaction norm approach. Both consistent and flexible reaction norm expression has been argued to serve adaptive purposes, depending on the stability and predictability of environmental conditions. Here, we investigated both trait and reaction norm repeatability of urinary cortisol levels in wild adult male chimpanzees. To capture the expression of the circadian urinary cortisol rhythm of individual males over time, urine samples were collected throughout the day. In total data of 30 males collected over a period of 8 years were included in the dataset. No male was sampled over the whole 8-year period however. We found minor levels of trait repeatability but considerable reaction norm repeatability. This implies a minor role of genetic or priming factors on cortisol excretion, but reveals that males differ consistently in average urinary cortisol levels and the shape of the circadian urinary cortisol rhythm. Relating these results to fitness parameters will provide answers to questions on the adaptive value of reaction norm repeatability of this labile hormonal trait in the future.

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“…As an example of the latter, nonalcoholic sons of alcoholic fathers have altered HPA responsiveness to alcohol and mu opioid receptor antagonism compared to sons of nonalcoholic fathers (King et al, 1998;Schuckit et al, 1987;Wand et al, 1998). In fact, up to 50% of interindividual differences in basal and stress-induced cortisol levels in healthy human volunteers may be explained by genetic factors (Federenko et al, 2004;Linkowski et al, 1993). While this is likely due to the interaction of several genes, so too are the genetic determinants of drug addiction.…”

Section: Introductionmentioning

confidence: 99%

Altered Levels of Basal Cortisol in Healthy Subjects with a 118G Allele in Exon 1 of the Mu Opioid Receptor Gene

Bart

LaForge

Borg

et al. 2006

Neuropsychopharmacol

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The mu opioid receptor is centrally involved in the development of the addictive diseases. It also modulates the stress responsive hypothalamic-pituitary-adrenal axis. Receptors encoded by the variant 118G polymorphism in exon 1 of the mu opioid receptor gene have a threefold increase in beta-endorphin binding and beta-endorphin is three times more potent in receptor-mediated activation of G protein-coupled inwardly rectifying potassium channels. Humans with this variant have increased stress response following opioid antagonism. Here, we study basal levels of adrenocorticotropic hormone and cortisol in subjects with this variant. In all, 59 healthy adults were genotyped and had morning levels of adrenocorticotropic hormone and cortisol measured following intravenous administration of saline placebo. Subjects with a 118G allele had significantly greater levels of cortisol than subjects with the prototype gene. Groups did not differ in levels of adrenocorticotropic hormone. A planned comparison revealed significantly greater cortisol in females with at least one copy of the 118G allele compared to females with the prototype gene. There was no significant effect of gender alone, nor was there a significant interaction between gender and genotype, on ACTH or cortisol. Subjects with at least one copy of the 118G allele have increased basal levels of cortisol, which may influence the susceptibility to and treatment of the stress responsive dyscrasia.

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Twin study of the 24-h cortisol profile: evidence for genetic control of the human circadian clock

Cited by 106 publications

References 2 publications

Discovering Endophenotypes for Major Depression

Discovering Endophenotypes for Major Depression

Circadian Rhythms of Urinary Cortisol Levels Vary Between Individuals in Wild Male Chimpanzees: A Reaction Norm Approach

Altered Levels of Basal Cortisol in Healthy Subjects with a 118G Allele in Exon 1 of the Mu Opioid Receptor Gene

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