Supersensitivity to light: possible trait marker for manic-depressive illness

Lewy, Alfred J.; Nürnberger, John I.; Wehr, Thomas A.; Pack, David L.; Becker, Linda; Powell, Ruffin; Newsome, David A.

doi:10.1176/ajp.142.6.725

Cited by 245 publications

(17 citation statements)

References 22 publications

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“…Young subjects who are at high risk of affective disorder as well as euthymic BD patients showed an increased sensitivity to light suppression of melatonin, suggesting that this could be an endophenotype vulnerability marker in those patients [124,125,126]. Changes in 24-hour temperature and hormonal secretion have been noted in bipolar patients.…”

Section: The Phenome Of Bd From the Ion Channel Perspectivementioning

confidence: 99%

Variants in Ion Channel Genes Link Phenotypic Features of Bipolar Illness to Specific Neurobiological Process Domains

2015

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Recent advances in genome-wide association studies are pointing towards a major role for voltage-gated ion channels in neuropsychiatric disorders and, in particular, bipolar disorder (BD). The phenotype of BD is complex, with symptoms during mood episodes and deficits persisting between episodes. We have tried to elucidate the common neurobiological mechanisms associated with ion channel signaling in order to provide a new perspective on the clinical symptoms and possible endophenotypes seen in BD patients. We propose a model in which the multiple variants in genes coding for ion channel proteins would perturb motivational circuits, synaptic plasticity, myelination, hypothalamic-pituitary-adrenal axis function, circadian neuronal rhythms, and energy regulation. These changes in neurobiological mechanisms would manifest in endophenotypes of aberrant reward processing, white matter hyperintensities, deficits in executive function, altered frontolimbic connectivity, increased amygdala activity, increased melatonin suppression, decreased REM latency, and aberrant myo-inositol/ATP shuttling. The endophenotypes result in behaviors of poor impulse control, motivational changes, cognitive deficits, abnormal stress response, sleep disturbances, and energy changes involving different neurobiological process domains. The hypothesis is that these disturbances start with altered neural circuitry during development, following which multiple environmental triggers may disrupt the neuronal excitability balance through an activity-dependent molecular process, resulting in clinical mood episodes.

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Section: The Phenome Of Bd From the Ion Channel Perspectivementioning

confidence: 99%

Variants in Ion Channel Genes Link Phenotypic Features of Bipolar Illness to Specific Neurobiological Process Domains

2015

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“…For instance, BD subjects had decreased melatonin levels in response to a light night (Nurnberger et al, 2000) as well as increased melatonin suppression to light (Nathan et al, 1999). These findings suggest a genetic trait marker in BD (Hallam et al, 2006; Hallam et al, 2005c; Kennedy et al, 1996; Lewy et al, 1985; Nurnberger et al, 1988; Whalley et al, 1991). A polymorphism in the GPR50 (H9, melatonin-related receptor) was associated with increased risk for BD, but this finding was not subsequently replicated (Alaerts et al, 2006; Thomson et al, 2005).…”

Section: Therapeutic Targets For Rapid Antidepressant Efficacy Beymentioning

confidence: 73%

“…Interestingly, studies have shown that during depressive and manic episodes, individuals with mood disorders have abnormal circadian rhythm and changes in sleep patterns; these abnormalities include sleep-wake irregularities (Gruber et al, 2009; Harvey, 2008; Salvatore et al, 2008), abnormal actimetric parameters (Millan et al, 2005), and circadian preference for evening (Ahn et al, 2008; Mansour et al, 2005; Wood et al, 2009). Supersensitivity to melatonin suppression by light has also been observed in BD subjects, monozygotic twins discordant for BD, and the non-affected offspring of individuals with BD, but these findings were not confirmed in a similar study evaluating euthymic BD subjects (Hallam et al, 2005c; Lewy et al, 1985; Lewy et al, 1981; Nurnberger et al, 2000). The evidence suggests that regulation of sleep homeostasis is critical to achieving and maintaining remission in subjects with mood disorders.…”

Section: Therapeutic Targets For Rapid Antidepressant Efficacy Beymentioning

confidence: 89%

New targets for rapid antidepressant action

Machado‐Vieira

Henter

Zarate

2017

Progress in Neurobiology

127

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Current therapeutic options for major depressive disorder (MDD) and bipolar disorder (BD) are associated with a lag of onset that can prolong distress and impairment for patients, and their antidepressant efficacy is often limited. All currently approved antidepressant medications for MDD act primarily through monoaminergic mechanisms. Glutamate is the major excitatory neurotransmitter in the central nervous system, and glutamate and its cognate receptors are implicated in the pathophysiology of MDD, and in the development of novel therapeutics for this disorder. The rapid and robust antidepressant effects of the N-methyl-D-aspartate (NMDA) antagonist ketamine were first observed in 2000. Since then, other NMDA receptor antagonists have been studied in MDD. Most have demonstrated relatively modest antidepressant effects compared to ketamine, but some have shown more favorable characteristics. This article reviews the clinical evidence supporting the use of novel glutamate receptor modulators with direct affinity for cognate receptors: 1) non-competitive NMDA receptor antagonists (ketamine, memantine, dextromethorphan, AZD6765); 2) subunit (GluN2B)-specific NMDA receptor antagonists (CP-101,606/traxoprodil, MK-0657); 3) NMDA receptor glycine-site partial agonists (GLYX-13); and 4) metabotropic glutamate receptor (mGluR) modulators (AZD2066, RO4917523/basimglurant). We also briefly discuss several other theoretical glutamate receptor targets with preclinical antidepressant-like efficacy that have yet to be studied clinically; these include α-amino-3-hydroxyl-5-methyl-4-isoxazoleproprionic acid (AMPA) agonists and mGluR2/3 negative allosteric modulators. The review also discusses other promising, non-glutamatergic targets for potential rapid antidepressant effects, including the cholinergic system (scopolamine), the opioid system (ALKS-5461), corticotropin releasing factor (CRF) receptor antagonists (CP-316,311), and others.

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“…Because cortisol and its circadian rhythms are closely related to various mental states such as stress42, major depression4344, post-traumatic stress disorder4546, and BD4748, it is important to study the relationship between the circadian rhythm of cortisol and the risk of BD. Interestingly, studies on plasma melatonin levels suggest that hypersensitivity to light may be a possible marker for manic-depressive illness4950. Numberger et al reported a hypersensitivity to melatonin suppression by light in young, healthy people at high risk for major affective disorders51.…”

Section: Discussionmentioning

confidence: 99%

Molecular circadian rhythm shift due to bright light exposure before bedtime is related to subthreshold bipolarity

Cho

Moon

Yoon

et al. 2016

Sci Rep

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This study examined the link between circadian rhythm changes due to bright light exposure and subthreshold bipolarity. Molecular circadian rhythms, polysomnography, and actigraphy data were studied in 25 young, healthy male subjects, divided into high and low mood disorder questionnaire (MDQ) score groups. During the first 2 days of the study, the subjects were exposed to daily-living light (150 lux) for 4 hours before bedtime. Saliva and buccal cells were collected 5 times a day for 2 consecutive days. During the subsequent 5 days, the subjects were exposed to bright light (1,000 lux), and saliva and buccal cell samples were collected in the same way. Molecular circadian rhythms were analyzed using sine regression. Circadian rhythms of cortisol (F = 16.956, p < 0.001) and relative PER1/ARNTL gene expression (F = 122.1, p < 0.001) showed a delayed acrophase in both groups after bright light exposure. The high MDQ score group showed a significant delay in acrophase compared to the low MDQ score group only in salivary cortisol (F = 8.528, p = 0.008). The high MDQ score group showed hypersensitivity in cortisol rhythm shift after bright light exposure, suggesting characteristic molecular circadian rhythm changes in the high MDQ score group may be related to biological processes downstream from core circadian clock gene expression.

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Supersensitivity to light: possible trait marker for manic-depressive illness

Cited by 245 publications

References 22 publications

Variants in Ion Channel Genes Link Phenotypic Features of Bipolar Illness to Specific Neurobiological Process Domains

Variants in Ion Channel Genes Link Phenotypic Features of Bipolar Illness to Specific Neurobiological Process Domains

New targets for rapid antidepressant action

Molecular circadian rhythm shift due to bright light exposure before bedtime is related to subthreshold bipolarity

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