Circadian Clock and Stress Interactions in the Molecular Biology of Psychiatric Disorders

Landgraf, Dominic; McCarthy, Michael J.; Welsh, David K.

doi:10.1007/s11920-014-0483-7

Cited by 144 publications

(106 citation statements)

References 125 publications

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“…These processes may in turn feedback to impact clock function as well. For example, disruption of circadian rhythms is a hallmark of most neuropsychiatric disorders, including bipolar disorder (BD) (Landgraf et al, 2014a;McCarthy and Welsh, 2012;Wulff et al, 2010), a disabling condition characterized by episodes of depression and mania. The mechanisms by which circadian and mood-regulating processes influence each other are unclear (Landgraf et al, 2014b).…”

Section: Introductionmentioning

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: Introductionmentioning

confidence: 99%

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

et al. 2016

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“…Consequently, GC release shows a pronounced circadian rhythm, with peak levels in the early morning, promoting arousal after sleep and gluconeogenesis after overnight fasting [81]. as GR sensitivity across the day [83]. Conversely, GCs feedback on the clock, having an important role in synchronizing peripheral oscillators [83,84] via GC responsive elements (GREs) in the promoter regions of several clock genes.…”

Section: The Stress System: Glucocorticoidsmentioning

confidence: 99%

“…as GR sensitivity across the day [83]. Conversely, GCs feedback on the clock, having an important role in synchronizing peripheral oscillators [83,84] via GC responsive elements (GREs) in the promoter regions of several clock genes.…”

Section: The Stress System: Glucocorticoidsmentioning

confidence: 99%

“…Glucose homeostasis is achieved in part via suppression of Pck1 expression by the CRY genes [79]. Chronic activation of pulsatile GC release in response to stress can alter the circadian release of GCs, and this aberrant regulation of the HPA axis has been identified as a common pathway in both metabolic and neuropsychiatric syndromes, such as diabetes, obesity, and mood disorders [83,86]. Abdominal obesity is associated with abnormal diurnal variation of GC release, with increased basal and stress-induced GC levels [87].…”

Section: The Stress System: Glucocorticoidsmentioning

confidence: 99%

“…TH expression is controlled by GC hormones, and exposure to repeated or chronic stress is associated with increased TH expression. In addition, elevated CRF or GC receptor inactivation affects the sensitivity of DA-dependent reward pathways [38,83]. Evidence indicates that leptin´s modulation of feeding behavior is in part due to its action on VTA DA neurons.…”

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confidence: 99%

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Circadian Clocks as Modulators of Metabolic Comorbidity in Psychiatric Disorders

Barandas

Landgraf

McCarthy

et al. 2015

Curr Psychiatry Rep

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Psychiatric disorders such as schizophrenia, bipolar disorder, and major depressive disorder are often accompanied by metabolic dysfunction symptoms, including obesity and diabetes. Since the circadian system controls important brain systems that regulate affective, cognitive, and metabolic functions, and neuropsychiatric and metabolic diseases are often correlated with disturbances of circadian rhythms, we hypothesize that dysregulation of circadian clocks plays a central role in metabolic comorbidity in psychiatric disorders. In this review paper, we highlight the role of circadian clocks in glucocorticoid, dopamine, and orexin/melanin-concentrating hormone systems, and describe how a dysfunction of these clocks may contribute to the simultaneous development of psychiatric and metabolic symptoms.3

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Real-time Mobile Monitoring of the Dynamic Associations Among Motor Activity, Energy, Mood, and Sleep in Adults With Bipolar Disorder

et al. 2019

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IMPORTANCE Biologic systems involved in the regulation of motor activity are intricately linked with other homeostatic systems such as sleep, feeding behavior, energy, and mood. Mobile monitoring technology (eg, actigraphy and ecological momentary assessment devices) allows the assessment of these multiple systems in real time. However, most clinical studies of mental disorders that use mobile devices have not focused on the dynamic associations between these systems. OBJECTIVES To examine the directional associations among motor activity, energy, mood, and sleep using mobile monitoring in a community-identified sample, and to evaluate whether these within-day associations differ between people with a history of bipolar or other mood disorders and controls without mood disorders.

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Circadian Clock and Stress Interactions in the Molecular Biology of Psychiatric Disorders

Cited by 144 publications

References 125 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 Clocks as Modulators of Metabolic Comorbidity in Psychiatric Disorders

Real-time Mobile Monitoring of the Dynamic Associations Among Motor Activity, Energy, Mood, and Sleep in Adults With Bipolar Disorder

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