Precision Light for the Treatment of Psychiatric Disorders

Abstract

Circadian timekeeping can be reset by brief flashes of light using stimulation protocols thousands of times shorter than those previously assumed to be necessary for traditional phototherapy. These observations point to a future where flexible architectures of nanosecond-, microsecond-, and millisecond-scale light pulses are compiled to reprogram the brain's internal clock when it has been altered by psychiatric illness or advanced age. In the current review, we present a chronology of seminal experiments that established the synchronizing influence of light on the human circadian system and the efficacy of prolonged bright-light exposure for reducing symptoms associated with seasonal affective disorder. We conclude with a discussion of the different ways that precision flashes could be parlayed during sleep to effect neuroadaptive changes in brain function. This article is a contribution to a special issue on Circadian Rhythms in Regulation of Brain Processes and Role in Psychiatric Disorders curated by editors Shimon Amir, Karen Gamble, Oliver Stork, and Harry Pantazopoulos.

Responses to Intermittent Light Stimulation Late in the Night Phase Before Dawn

“…In sum, our results Precious few studies have attempted to distinguish how light differentially impacts phase resetting of the E and M oscillator. Those that have are in general agreement with our results that the M oscillator's responses are less energy dependent than those of the E oscillator [35,36], but have not probed much further to look at differences in how these subsystems process other characteristics of light-conceivably a massive parameter space involving syllables (i.e., intermittent bytes of photic information) with different pulse shapes and length, intensities, color enrichment, and delivery intervals [37]. Inspired by the natural asymmetries in light and color perception that occur at dawn versus dusk [53], we quantified in the current study the M oscillator's responses to over a dozen patterns of intermittent light administration at ZT23 (an hour before lights-on or "dawn") and benchmarked them against a previous study from our laboratory that evaluated the E oscillator's responses to the same protocols at ZT13 (an hour after lights-off or "dusk") [40].…”

“…While appreciable effort has gone into characterizing the cellular and molecular origins of the pacemaker's E and M oscillators, considerably less so has been given to defining the extent to which each subsystem differs in its responses to light (beyond phase directionality). This question, which has been woefully unaddressed over the past 30-40 years in particular [34][35][36], is newly relevant given recent studies demonstrating the inordinate phase-shifting effects of intermittent light stimulation [37][38][39][40][41][42][43][44][45][46]. For example, when millisecond flashes are delivered once-every-second or once-every-several-seconds to flies [40,41], common laboratory rodents [42][43][44], or people [45,46], they will produce a phase jump nearly identical to that produced by nonstop illumination over the same administration period-despite the massive difference in exposure.…”

ADHD 24/7: Circadian clock genes, chronotherapy and sleep/wake cycle insufficiencies in ADHD

“…The susceptibility of the circadian clock to be shifted by time-specific light exposure is thoroughly studied and is broadly utilized in treatment protocols of sleep-phase and depressive disorders, e.g., SAD (Gooley, 2008;Kaladchibachi & Fernandez, 2018;Oldham & Ciraulo, 2014). Long-term light interventions effectively advance sleep onset time (van Maanen, et al, 2016;Watanabe, Kajimura, Kato, Sekimoto, & Takahashi, 1999) as well as result in less sleepiness after awakening in neurotypical adults with DSPD (Lack, et al, 2007;Van De Werken, et al, 2010), for a review see (Figueiro, 2016).…”

“…Indeed, due to the lack of an obvious type of placebo treatment, LT studies have been extensively criticized for their flawed experimental design. And yet, at least for the treatment of seasonal and non-seasonal depression, an accumulated bulk of randomized and double-blind clinical trials approves the utility of LT and invites further studies in other psychiatric, neurodevelopmental and neurocognitive disorders (for review see (Kaladchibachi & Fernandez, 2018)).…”

“…The symptomatology of ADHD may be positively influenced by shifting misaligned circadian rhythms to more appropriate phase, through pharmacological or behavioural interventions (Mayer et al, 2018). A successful therapy to influence the circadian rhythm via changes in the expression of relevant genes, for example, in seasonal depression, is bright light (BL) therapy, and thus it might be useful for the treatment of ADHD (Kaladchibachi & Fernandez, 2018;Pail et al, 2011). A recent position paper of physicians and researchers from the EU has addressed the need to explore and develop light based interventions to ameliorate ADHD (Coogan, Baird, Popa-Wagner, & Thome, 2016).…”