The circadian basis of winter depression

Lewy, Alfred J.; Lefler, Bryan J.; Emens, Jonathan S.; Bauer, Vance K.

doi:10.1073/pnas.0602425103

Cited by 386 publications

(298 citation statements)

References 39 publications

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“…Clinical response to mood stabilizers is not uniform: only about 1/3 of BD patients respond fully to lithium, and the clinical profiles that predict lithium vs. VPA response differ considerably (McCarthy et al, 2010). Accordingly, while many studies have reported a predisposition towards phase delay/long periods in BD, some have reported phase advance/short period in BD (Kripke et al, 1978;Salvatore et al, 2008) or other mood disorders (Lewy et al, 2006). Perhaps only a subset of patients with long period/phase delay benefit from the period-shortening effects of VPA, while a different subset with short period/phase advance benefit from lithium.…”

Section: Discussionmentioning

confidence: 99%

The mood stabilizer valproic acid opposes the effects of dopamine on circadian rhythms

et al. 2016

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a b s t r a c tEndogenous circadian (~24 h) clocks regulate key physiological and cognitive processes via rhythmic expression of clock genes. The main circadian pacemaker is the hypothalamic suprachiasmatic nucleus (SCN). Mood disorders, including bipolar disorder (BD), are commonly associated with disturbed circadian rhythms. Dopamine (DA) contributes to mania in BD and has direct impact on clock gene expression. Therefore, we hypothesized that high levels of DA during episodes of mania contribute to disturbed circadian rhythms in BD. The mood stabilizer valproic acid (VPA) also affects circadian rhythms. Thus, we further hypothesized that VPA normalizes circadian disturbances caused by elevated levels of DA. To test these hypotheses, we examined locomotor rhythms and circadian gene cycling in mice with reduced expression of the dopamine transporter (DAT-KD mice), which results in elevated DA levels and manialike behavior. We found that elevated DA signaling lengthened the circadian period of behavioral rhythms in DAT-KD mice and clock gene expression rhythms in SCN explants. In contrast, we found that VPA shortened circadian period of behavioral rhythms in DAT-KD mice and clock gene expression rhythms in SCN explants, hippocampal cell lines, and human fibroblasts from BD patients. Thus, DA and VPA have opposing effects on circadian period. To test whether the impact of VPA on circadian rhythms contributes to its behavioral effects, we fed VPA to DAT-deficient Drosophila with and without functioning circadian clocks. Consistent with our hypothesis, we found that VPA had potent activity-suppressing effects in hyperactive DAT-deficient flies with intact circadian clocks. However, these effects were attenuated in DAT-deficient flies in which circadian clocks were disrupted, suggesting that VPA functions partly through the circadian clock to suppress activity. Here, we provide in vivo and in vitro evidence across species that elevated DA signaling lengthens the circadian period, an effect remediated by VPA treatment. Hence, VPA may exert beneficial effects on mood by normalizing lengthened circadian rhythm period in subjects with elevated DA resulting from reduced DAT.

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Section: Discussionmentioning

confidence: 99%

The mood stabilizer valproic acid opposes the effects of dopamine on circadian rhythms

et al. 2016

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“…Therefore, the early morning light is leading to a phase advance in the circadian system putting it back on track with the sleep/wake cycle. In addition, there have been reports that melatonin therapy in the evening can also be effective in producing this same phase advance and may help with the treatment of SAD (Lewy et al, 1998a;Lewy et al, 2006). Though this theory has a lot of support, it still remains controversial.…”

Section: Seasonal Affective Disordermentioning

confidence: 99%

“…However, in some studies, evening light exposure has an equally strong antidepressant effect as morning exposure and several studies find no therapeutic effects of melatonin treatment (Wirz-Justice et al, 1990;Wirz-Justice et al, 1993;Terman et al, 2001). Other theories suggest that SAD patients actually fall into two categories, some with a phase delay in rhythms and some with a phase advance in rhythms (Boivin, 2000;Lewy et al, 2006). The timing of light therapy and perhaps melatonin therapy would then need to be adjusted for each group separately to produce the desired shift in rhythms and therapeutic effects.…”

Section: Seasonal Affective Disordermentioning

confidence: 99%

Circadian genes, rhythms and the biology of mood disorders

McClung

2007

Pharmacology & Therapeutics

574

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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“…Most SAD patients become depressed in the winter time because of the later dawn, which leads their circadian rhythms to delay with respect to both clock time and to the sleep-wake cycle [45]. Changes in the latter sleep-wake are apparent, with most patients presenting hypersomnia in conjunction with EDS.…”

Section: Depression and Circadian Rhythmsmentioning

confidence: 99%

Chronobiology, excessive daytime sleepiness and depression: Is there a link?

2009

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The complaint of excessive daytime sleepiness (EDS), commonly encountered in clinical practice, may arise from a variety of psychiatric disorders, most importantly depression. Even though EDS frequently leads depressed patients to seek medical assistance, it is commonly under-evaluated and under-diagnosed. Therefore, a comprehensive understanding and management of EDS is essential in the clinical assessment of depression. Within a theoretical framework, a chronobiological approach may shed new light on the complex interaction of EDS and depression. In this review, studies on EDS and depression are summarized and discussed within the context of circadian and sleep regulatory mechanisms. Furthermore, potential chronobiological therapeutic strategies are proposed to address some of the unmet needs in the treatment of EDS and depression.

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The circadian basis of winter depression

Cited by 386 publications

References 39 publications

The mood stabilizer valproic acid opposes the effects of dopamine on circadian rhythms

The mood stabilizer valproic acid opposes the effects of dopamine on circadian rhythms

Circadian genes, rhythms and the biology of mood disorders

Chronobiology, excessive daytime sleepiness and depression: Is there a link?

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