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Photoperiodic and circadian bifurcation theories of depression and mania.

Kripke DF, Elliott JA, Welsh DK, Youngstedt SD - F1000Res (2015)

Bottom Line: Seasonal effects on mood have been observed throughout much of human history.  Seasonal changes in animals and plants are largely mediated through the changing photoperiod (i.e., the photophase or duration of daylight).  We review that in mammals, daylight specifically regulates SCN (suprachiasmatic nucleus) circadian organization and its control of melatonin secretion.  The timing of melatonin secretion interacts with gene transcription in the pituitary pars tuberalis to modulate production of TSH (thyrotropin), hypothalamic T3 (triiodothyronine), and tuberalin peptides which modulate pituitary production of regulatory gonadotropins and other hormones.  Pituitary hormones largely mediate seasonal physiologic and behavioral variations.  As a result of long winter nights or inadequate illumination, we propose that delayed morning offset of nocturnal melatonin secretion, suppressing pars tuberalis function, could be the main cause for winter depression and even cause depressions at other times of year.  Irregularities of circadian sleep timing and thyroid homeostasis contribute to depression.  Bright light and sleep restriction are antidepressant and conversely, sometimes trigger mania.  We propose that internal desynchronization or bifurcation of SCN circadian rhythms may underlie rapid-cycling manic-depressive disorders and perhaps most mania.  Much further research will be needed to add substance to these theories.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry and Center for Circadian Biology, University of California, San Diego, CA, 92093-0603, USA.

ABSTRACT
Seasonal effects on mood have been observed throughout much of human history.  Seasonal changes in animals and plants are largely mediated through the changing photoperiod (i.e., the photophase or duration of daylight).  We review that in mammals, daylight specifically regulates SCN (suprachiasmatic nucleus) circadian organization and its control of melatonin secretion.  The timing of melatonin secretion interacts with gene transcription in the pituitary pars tuberalis to modulate production of TSH (thyrotropin), hypothalamic T3 (triiodothyronine), and tuberalin peptides which modulate pituitary production of regulatory gonadotropins and other hormones.  Pituitary hormones largely mediate seasonal physiologic and behavioral variations.  As a result of long winter nights or inadequate illumination, we propose that delayed morning offset of nocturnal melatonin secretion, suppressing pars tuberalis function, could be the main cause for winter depression and even cause depressions at other times of year.  Irregularities of circadian sleep timing and thyroid homeostasis contribute to depression.  Bright light and sleep restriction are antidepressant and conversely, sometimes trigger mania.  We propose that internal desynchronization or bifurcation of SCN circadian rhythms may underlie rapid-cycling manic-depressive disorders and perhaps most mania.  Much further research will be needed to add substance to these theories.

No MeSH data available.


Related in: MedlinePlus

Delayed sleep phase (DSP) and photoperiodic disturbances.A, Depicted is some of the circadian gene network that times transcription through pathways leading to E-box activation (green) or which deactivates transcription and E-box promoter action (red) in a night owl or depressed person.B, The yellow line illustrates normal melatonin secretion commencing shortly before the preferred nocturnal sleep time and terminating about the time of awakening near dawn, so that preferred sleep times and sleepiness normally correspond. The yellow dotted line illustrates how in DSP, melatonin secretion offset may become delayed, with correspondingly delayed sleep propensity.C, The geneEYA3 reaches a sharp peak in pars tuberalis transcription about 12 hours after darkness onset (solid orange line), but if melatonin is still elevated (due to long nights of winter, long time in bed, or DSP), the EYA3 peak is largely suppressed (dashed orange line). Bright lights (light bulb and sun symbols) conversely suppress and advance melatonin offset (red arrows), disinhibiting EYA3.D, After short nights in summer, EYA3, SIX1 and TEF coactivate near a D-box on theTSHB promoter. TSHB hybridizes with TSHA, releasing active TSH into 3rd ventricle CSF6,44.E, TSH circulates retrograde to promote DIO2 which converts T4 to T3.F, T3 promotes synthesis and release of gonadotropin hormones, implementing summer reproduction and good mood. Revised with permission from Kripkeet al.,Psychiat. Invest., 201499.
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f1: Delayed sleep phase (DSP) and photoperiodic disturbances.A, Depicted is some of the circadian gene network that times transcription through pathways leading to E-box activation (green) or which deactivates transcription and E-box promoter action (red) in a night owl or depressed person.B, The yellow line illustrates normal melatonin secretion commencing shortly before the preferred nocturnal sleep time and terminating about the time of awakening near dawn, so that preferred sleep times and sleepiness normally correspond. The yellow dotted line illustrates how in DSP, melatonin secretion offset may become delayed, with correspondingly delayed sleep propensity.C, The geneEYA3 reaches a sharp peak in pars tuberalis transcription about 12 hours after darkness onset (solid orange line), but if melatonin is still elevated (due to long nights of winter, long time in bed, or DSP), the EYA3 peak is largely suppressed (dashed orange line). Bright lights (light bulb and sun symbols) conversely suppress and advance melatonin offset (red arrows), disinhibiting EYA3.D, After short nights in summer, EYA3, SIX1 and TEF coactivate near a D-box on theTSHB promoter. TSHB hybridizes with TSHA, releasing active TSH into 3rd ventricle CSF6,44.E, TSH circulates retrograde to promote DIO2 which converts T4 to T3.F, T3 promotes synthesis and release of gonadotropin hormones, implementing summer reproduction and good mood. Revised with permission from Kripkeet al.,Psychiat. Invest., 201499.

Mentions: The duration of nocturnal melatonin secretion regulates seasonal gonadal growth and breeding through hypothalamic regulation of the most active thyroid hormone, T3 (triiodothyronine); as will be discussed, T3 is likewise crucial to mood. The importance of T3 in photoperiodic control was recognized in Japanese quail41 and then confirmed in mammalian species. In mammals, melatonin binds to a dense supply of melatonin receptors in the pars tuberalis (PT) in the rostral anterior pituitary just below the hypothalamic median eminence42. A primary effect of melatonin in PT is control of the transcription factorEYA3 (Figure 1). In the summer when the interval of melatonin secretion ends early,EYA3 is strongly transcribed in PT in the early morning about 12 hours after dark, a time when circulating melatonin is low43. While TEF binds to a D-Box motif on theTSHB promoter in PT, SIX1 binds to an adjacent So1 site on the promoter, and EYA3 binds either to SIX1 or to a nearby site on theTSHB promoter5,6. Together, EYA3, SIX1, and TEF combine to promote pars tuberalis transcription of theTSHB gene.TSHB transcription leads to translation of the thyroid stimulating hormone beta chain, which hybridizes with the TSHA polypeptide to form the active dimer, thyroid stimulating hormone (TSH). PT TSH then passes retrograde into the 3rd cerebral ventricle CSF5,6,18,44. Very high local concentrations of TSH in the 3rd ventricle bind to TSH receptors on ependymal tanycytes lining the ventricular surface, which in turn promotes transcription of a deiodinase (DIO2) that converts T4 to T3, especially in the tanycytes. This produces high concentrations of T3 in the third ventricle and adjacent hypothalamic region, close to TRH (thyrotropin releasing hormone) cells which homeostatically respond to T3 feedback41,43,45. Since T3 passes into the brain poorly, most brain T3 is produced within the brain and substantial portions by these 3rd ventricle tanycytes46. PT production of TSH is not influenced by homeostatic feedback from TRH and T3, and unique PT glycosylation of TSH prevents the small amounts of TSH produced by PT from directly influencing the thyroid47.


Photoperiodic and circadian bifurcation theories of depression and mania.

Kripke DF, Elliott JA, Welsh DK, Youngstedt SD - F1000Res (2015)

Delayed sleep phase (DSP) and photoperiodic disturbances.A, Depicted is some of the circadian gene network that times transcription through pathways leading to E-box activation (green) or which deactivates transcription and E-box promoter action (red) in a night owl or depressed person.B, The yellow line illustrates normal melatonin secretion commencing shortly before the preferred nocturnal sleep time and terminating about the time of awakening near dawn, so that preferred sleep times and sleepiness normally correspond. The yellow dotted line illustrates how in DSP, melatonin secretion offset may become delayed, with correspondingly delayed sleep propensity.C, The geneEYA3 reaches a sharp peak in pars tuberalis transcription about 12 hours after darkness onset (solid orange line), but if melatonin is still elevated (due to long nights of winter, long time in bed, or DSP), the EYA3 peak is largely suppressed (dashed orange line). Bright lights (light bulb and sun symbols) conversely suppress and advance melatonin offset (red arrows), disinhibiting EYA3.D, After short nights in summer, EYA3, SIX1 and TEF coactivate near a D-box on theTSHB promoter. TSHB hybridizes with TSHA, releasing active TSH into 3rd ventricle CSF6,44.E, TSH circulates retrograde to promote DIO2 which converts T4 to T3.F, T3 promotes synthesis and release of gonadotropin hormones, implementing summer reproduction and good mood. Revised with permission from Kripkeet al.,Psychiat. Invest., 201499.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4490783&req=5

f1: Delayed sleep phase (DSP) and photoperiodic disturbances.A, Depicted is some of the circadian gene network that times transcription through pathways leading to E-box activation (green) or which deactivates transcription and E-box promoter action (red) in a night owl or depressed person.B, The yellow line illustrates normal melatonin secretion commencing shortly before the preferred nocturnal sleep time and terminating about the time of awakening near dawn, so that preferred sleep times and sleepiness normally correspond. The yellow dotted line illustrates how in DSP, melatonin secretion offset may become delayed, with correspondingly delayed sleep propensity.C, The geneEYA3 reaches a sharp peak in pars tuberalis transcription about 12 hours after darkness onset (solid orange line), but if melatonin is still elevated (due to long nights of winter, long time in bed, or DSP), the EYA3 peak is largely suppressed (dashed orange line). Bright lights (light bulb and sun symbols) conversely suppress and advance melatonin offset (red arrows), disinhibiting EYA3.D, After short nights in summer, EYA3, SIX1 and TEF coactivate near a D-box on theTSHB promoter. TSHB hybridizes with TSHA, releasing active TSH into 3rd ventricle CSF6,44.E, TSH circulates retrograde to promote DIO2 which converts T4 to T3.F, T3 promotes synthesis and release of gonadotropin hormones, implementing summer reproduction and good mood. Revised with permission from Kripkeet al.,Psychiat. Invest., 201499.
Mentions: The duration of nocturnal melatonin secretion regulates seasonal gonadal growth and breeding through hypothalamic regulation of the most active thyroid hormone, T3 (triiodothyronine); as will be discussed, T3 is likewise crucial to mood. The importance of T3 in photoperiodic control was recognized in Japanese quail41 and then confirmed in mammalian species. In mammals, melatonin binds to a dense supply of melatonin receptors in the pars tuberalis (PT) in the rostral anterior pituitary just below the hypothalamic median eminence42. A primary effect of melatonin in PT is control of the transcription factorEYA3 (Figure 1). In the summer when the interval of melatonin secretion ends early,EYA3 is strongly transcribed in PT in the early morning about 12 hours after dark, a time when circulating melatonin is low43. While TEF binds to a D-Box motif on theTSHB promoter in PT, SIX1 binds to an adjacent So1 site on the promoter, and EYA3 binds either to SIX1 or to a nearby site on theTSHB promoter5,6. Together, EYA3, SIX1, and TEF combine to promote pars tuberalis transcription of theTSHB gene.TSHB transcription leads to translation of the thyroid stimulating hormone beta chain, which hybridizes with the TSHA polypeptide to form the active dimer, thyroid stimulating hormone (TSH). PT TSH then passes retrograde into the 3rd cerebral ventricle CSF5,6,18,44. Very high local concentrations of TSH in the 3rd ventricle bind to TSH receptors on ependymal tanycytes lining the ventricular surface, which in turn promotes transcription of a deiodinase (DIO2) that converts T4 to T3, especially in the tanycytes. This produces high concentrations of T3 in the third ventricle and adjacent hypothalamic region, close to TRH (thyrotropin releasing hormone) cells which homeostatically respond to T3 feedback41,43,45. Since T3 passes into the brain poorly, most brain T3 is produced within the brain and substantial portions by these 3rd ventricle tanycytes46. PT production of TSH is not influenced by homeostatic feedback from TRH and T3, and unique PT glycosylation of TSH prevents the small amounts of TSH produced by PT from directly influencing the thyroid47.

Bottom Line: Seasonal effects on mood have been observed throughout much of human history.  Seasonal changes in animals and plants are largely mediated through the changing photoperiod (i.e., the photophase or duration of daylight).  We review that in mammals, daylight specifically regulates SCN (suprachiasmatic nucleus) circadian organization and its control of melatonin secretion.  The timing of melatonin secretion interacts with gene transcription in the pituitary pars tuberalis to modulate production of TSH (thyrotropin), hypothalamic T3 (triiodothyronine), and tuberalin peptides which modulate pituitary production of regulatory gonadotropins and other hormones.  Pituitary hormones largely mediate seasonal physiologic and behavioral variations.  As a result of long winter nights or inadequate illumination, we propose that delayed morning offset of nocturnal melatonin secretion, suppressing pars tuberalis function, could be the main cause for winter depression and even cause depressions at other times of year.  Irregularities of circadian sleep timing and thyroid homeostasis contribute to depression.  Bright light and sleep restriction are antidepressant and conversely, sometimes trigger mania.  We propose that internal desynchronization or bifurcation of SCN circadian rhythms may underlie rapid-cycling manic-depressive disorders and perhaps most mania.  Much further research will be needed to add substance to these theories.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry and Center for Circadian Biology, University of California, San Diego, CA, 92093-0603, USA.

ABSTRACT
Seasonal effects on mood have been observed throughout much of human history.  Seasonal changes in animals and plants are largely mediated through the changing photoperiod (i.e., the photophase or duration of daylight).  We review that in mammals, daylight specifically regulates SCN (suprachiasmatic nucleus) circadian organization and its control of melatonin secretion.  The timing of melatonin secretion interacts with gene transcription in the pituitary pars tuberalis to modulate production of TSH (thyrotropin), hypothalamic T3 (triiodothyronine), and tuberalin peptides which modulate pituitary production of regulatory gonadotropins and other hormones.  Pituitary hormones largely mediate seasonal physiologic and behavioral variations.  As a result of long winter nights or inadequate illumination, we propose that delayed morning offset of nocturnal melatonin secretion, suppressing pars tuberalis function, could be the main cause for winter depression and even cause depressions at other times of year.  Irregularities of circadian sleep timing and thyroid homeostasis contribute to depression.  Bright light and sleep restriction are antidepressant and conversely, sometimes trigger mania.  We propose that internal desynchronization or bifurcation of SCN circadian rhythms may underlie rapid-cycling manic-depressive disorders and perhaps most mania.  Much further research will be needed to add substance to these theories.

No MeSH data available.


Related in: MedlinePlus