Rhythms and the pharmacology of lithium

Klemfuss, Harry

doi:10.1016/0163-7258(92)90037-z

Cited by 129 publications

(86 citation statements)

References 162 publications

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“…Interestingly, both of these drugs have been repeatedly shown to alter the circadian period, leading to a long period in Drosophila, non-human primates, rodents and humans (Johnsson et al, 1983;Welsh and Moore-Ede, 1990;Klemfuss, 1992;Hafen and Wollnik, 1994;Dokucu et al, 2005). This effect on circadian rhythms likely involves the inhibition of GSK3β which modifies multiple members of the molecular clock (Iwahana et al, 2004;Padiath et al, 2004;Gould and Manji, 2005;Iitaka et al, 2005;Yin et al, 2006).…”

Section: Pharmacological Treatmentsmentioning

confidence: 99%

Circadian genes, rhythms and the biology of mood disorders

McClung

2007

Pharmacology & Therapeutics

587

386

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For many years, researchers have suggested that abnormalities in circadian rhythms may underlie the development of mood disorders such as bipolar disorder, major depression and seasonal affective disorder. Furthermore, some of the treatments that are currently employed to treat mood disorders are thought to act by shifting or "resetting" the circadian clock, including total sleep deprivation and bright light therapy. There is also reason to suspect that many of the mood stabilizers and antidepressants used to treat these disorders may derive at least some of their therapeutic efficacy by affecting the circadian clock. Recent genetic, molecular and behavioral studies implicate individual genes that make up the clock in mood regulation. As well, important functions of these genes in brain regions and neurotransmitter systems associated with mood regulation is becoming apparent. In this review, the evidence linking circadian rhythms and mood disorders, and what is known about the underlying biology of this association, is presented.

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Section: Pharmacological Treatmentsmentioning

confidence: 99%

Circadian genes, rhythms and the biology of mood disorders

McClung

2007

Pharmacology & Therapeutics

587

386

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“…This is at least partly due to its robustness. Circadian behavior is impaired in patients with psychiatric disorders, especially affective disorders (Klemfuss, 1992;Bunney and Bunney, 2000;Leibenluft and Frank, 2001). In addition, circadian behavior is very highly conserved across phylogeny.…”

Section: Introductionmentioning

confidence: 99%

Lithium- and Valproate-Induced Alterations in Circadian Locomotor Behavior in Drosophila

Dokucu

Taghert

2005

Neuropsychopharmacol

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Lithium and valproate are commonly used mood stabilizers, but their action pathways are not clearly understood. They also suffer from multiple toxic effects that limit their utility. Elucidating their action mechanisms could lead to newer agents and better understanding of the etiopathogenesis of bipolar disorder. We have expanded the study of signaling mechanisms of lithium and valproate by using Drosophila circadian locomotor activity as a robust behavioral assay that is amenable to genetic manipulations. We demonstrate that lithium affects the circadian system of Drosophila similarly to what has been reported in the mammalian studies. We show that lithium and valproate share effects on the circadian locomotor activity of Drosophila: they lengthen the period of circadian rhythms and increase arrhythmicity. Valproate exerts these effects in a weaker fashion than does lithium. We also tested the circadian alterations in multiple mutant lines of Drosophila bearing defects in the GSK-3b gene and other clock genes in response to lithium administration. We show that lithium partially rescues the shortening of circadian period when the GSK-3b gene is overexpressed only in specific circadian pacemaker neurons, thus implicating GSK-3b as a component in lithium's effect on the circadian oscillator. Moreover, lithium also lengthens the period in GSK-3b heterozygous mutants and doubletime long mutants. These results establish a basis for using Drosophila genetics to investigate more fully lithium and valproate action mechanisms.

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“…Both of these drugs have been repeatedly shown to alter the circadian period, leading to a long period in Drosophila, nonhuman primates, rodents, and humans (Johnsson et al 1983;Welsh and Moore-Ede 1990;Klemfuss 1992;Hafen and Wollnik 1994;Dokucu et al 2005). Lithium is also able to slow the abnormally fast circadian rhythms found in most bipolar patients (Atkinson et al 1975;Kripke et al 1978).…”

Section: Treatments For Mood Disorders Involve the Clockmentioning

confidence: 99%

Role for theClockGene in Bipolar Disorder

McClung¹

2007

Cold Spring Harbor Symposia on Quantitative Biology

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Nearly all patients with bipolar disorder have severely disrupted circadian rhythms. Treatment with mood stabilizers can restore these daily rhythms, and this is correlated with patient recovery. However, it is still uncertain whether clock abnormalities are the cause of bipolar disorder or if these rhythm disruptions are secondary to alterations in other circuits. Furthermore, the mechanism by which the circadian clock might influence mood is still unclear. With cloning and characterization of the circadian genes and recent advances in molecular biology, we are starting to understand this strong association between circadian rhythms and bipolar disorder. Recent human genetic and mouse behavioral studies indicate that the Clock gene is particularly relevant in the mood disruptions associated with this disorder. Furthermore, it appears that Clock expression outside of the central pacemaker of the suprachiasmatic nucleus (SCN) is involved in mood regulation. In this chapter, the evidence linking circadian rhythms, the Clock gene, and bipolar disorder is discussed, along with the possible biology that underlies this connection.

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Rhythms and the pharmacology of lithium

Cited by 129 publications

References 162 publications

Circadian genes, rhythms and the biology of mood disorders

Circadian genes, rhythms and the biology of mood disorders

Lithium- and Valproate-Induced Alterations in Circadian Locomotor Behavior in Drosophila

Role for theClockGene in Bipolar Disorder

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