Lightening the mood: evidence for blue light exposure in the treatment of post-concussion depression

KEYWORDS:

• Depression
• mood disorders
• concussion
• mild traumatic brain injury
• mTBI
• light therapy
• blue light

1. Concussion and depression

Mild traumatic brain injury (mTBI), or concussion, is an exceptionally common injury during sports activities, but can also occur from falls, moving vehicle accidents, physical violence, or even explosive blasts. According to the CDC, upwards of 2.5 million Emergency Department visits occur annually as a result of TBI [1], and some estimates suggest that the prevalence of concussions could be much higher. An mTBI occurs when a person sustains an impact or other mechanical force to the head that leads to a brief alteration of consciousness or change of mental status, and associated cognitive or motor deficits [2]. While the vast majority of individuals who sustain an mTBI will recover rapidly and return to normal functioning within a matter of hours to days, a minority of those affected will continue to show lingering post-concussion symptoms that may last for months or even years after their injury [2]. Sleep disruption and mood difficulties are common symptoms that may persist long after sustaining an mTBI [3]. One recent study found that over 21% of people who had experienced an mTBI reported mental health concerns such as major depression six months after their injury [3], and others have found similar levels of depression persisting up to a year or more.

Selective serotonin reuptake inhibitors (SSRIs) are currently the first-line recommended treatment for depression in patients recovering from concussion [4]. However, despite their widespread use for treating depression in patients with and without neurologic conditions, a recent meta-analysis suggested that SSRIs were actually no more effective at reducing depressive symptoms in mTBI patients than placebo [5]. While caution is warranted in prematurely abandoning the use of SSRIs for this population, given that the benefits may still outweigh potential risks [4], these negative findings should motivate researchers to expand their horizons to identify additional therapeutic options for treating depression following concussion.

2. Light treatment for depression

One potential alternative to pharmacologic treatments for depression is light exposure therapy, which may provide an effective treatment option for some patients. The idea that light plays an important role in modulating mood is not new. It has long been established that some individuals are prone to a pattern of seasonal mood fluctuations, known as Seasonal Affective Disorder (SAD) [6], where depressed mood worsens during the darker months of fall and winter and improves as the hours of daylight increase in the spring and summer. The first-line treatment for SAD is daily morning exposure to light, typically using a large panel of bright white lights ranging in illuminance from 2,500 to 10,000 lux, with exposures lasting from 30 minutes to 2 hours each day [7]. Brighter light is generally believed to require a shorter exposure time to achieve a similar level of effectiveness. On the whole, at least half of patients with SAD show significant improvement in depressive symptoms with this kind of bright light treatment, and the effects are often apparent within only a matter of days [6]. Interestingly, it is now becoming evident that the effects may not be restricted only to patients with SAD, but light may also have similar mood-improving effects for those with non-seasonal mood disorders, including unipolar and bipolar depression [7,8]. Several meta-analytic studies demonstrate that daily exposure to light, particularly in the morning hours, can significantly reduce symptoms of non-seasonal depression, usually within as little as one week of treatment [6,7]. The rapidity of the effect, and the fact that light is a non-pharmacologic treatment that produces similar effect sizes to SSRIs, often with minimal side effects, makes it an ideal approach for many individuals with depression [6].

3. Mechanisms of action

While there are myriad ways that light can affect mood outcomes, there are at least two major brain systems through which light has its primary effects. The first, and most well studied, is the circadian system. The alternating 24-h cycle of night and day has remained essentially unchanged since life first began on Earth, and this rhythmicity is deeply ingrained within our DNA. Our cellular clocks maintain a near 24-h rhythm and are reset each day by exposure to light. Stimulation of this system begins when light strikes a particular type of pigmented receptor in the eye, known as an intrinsically photosensitive retinal ganglion cell (ipRGC). These cells are unique and independent from the primary image producing cells of the retina. The ipRGCs project primarily to the suprachiasmatic nucleus (SCN) of the hypothalamus, which serves as the body’s master time-keeper. The SCN regulates the production of the circadian regulating hormone melatonin by the pineal gland, and therefore, has a powerful influence over daily sleep-wake activity.

When ipRGCs are stimulated by bright light, particularly light in the blue wavelengths (~470 nm), the SCN will suppress ongoing melatonin production and shift the timing of future secretion of this sleep regulating hormone. Depending on the time of day when a person is exposed to light, melatonin secretion will be shifted either slightly forward or backward in the day. Brighter light typically has a greater melatonin suppressing and phase-shifting effect than light of lesser intensity. However, owing to the fact that ipRGCs are specifically attuned to respond to blue wavelengths, it is possible to obtain similar melatonin suppressing and phase-shifting effects with blue light of much lower intensity compared to much brighter white light. Light exposure in the morning will ‘phase advance’ this system so that melatonin onset will begin earlier the next evening, while light exposure occurring in the late day or evening will ‘phase delay’ the system so that melatonin onset will occur later at night. Regular exposure to bright light in the morning entrains the circadian rhythm for an earlier sleep onset and, therefore, a longer period of consolidated nighttime sleep. This ‘sleep reset’ effect appears to be associated with significant reduction in seasonal and non-seasonal depression [6]. Moreover, many patients recovering from a concussion experience frequent sleep problems, including a significant delay in the onset of rapid eye movement (REM) sleep and a decline in the total percentage of REM sleep during the night [9]. Sufficient high-quality sleep is vital for normal emotional function, and enhancing sleep is one potential way to help improve depression among those recovering from mTBI.

There is also a second brain system whereby light may affect mood. This brain system involves using light to stimulate monoaminergic systems involved in alertness and arousal [10]. Our own research, and that of many others suggests that mood and alertness are closely intertwined [11]. Using functional magnetic resonance imaging, we showed that 30 minutes of blue-wavelength light stimulation enhanced activation of the rostral anterior cingulate cortex (rACC) when participants were anticipating rewarding stimuli [12]. This brain region is important for expectations of pleasure [13] and is often reduced in volume in patients with depression [14]. Light appears to activate many of these positive emotion and cortical alerting systems almost immediately upon exposure [15,16]. This brain activation may be a second mechanism whereby light may enhance mood and reduce depression.

4. Applications to concussion

Although decades of evidence now suggest that light therapy is an effective alternative treatment for improving mood in many patients with SAD and non-seasonal depression, its effects in patients recovering from concussion have only just begun to be explored. Sinclair and colleagues found that daily morning blue light for four weeks was associated with reduced fatigue and daytime sleepiness in a sample of patients with a recent concussion [17]. Similarly, we recently showed that blue light treatment significantly phase advanced the circadian rhythm of individuals with a recent concussion, improved their daytime sleepiness, and increased the structural and functional connectivity between the posterior thalamus and cortical regions of the brain that are involved in attention [18]. We recently replicated the improvement in daytime sleepiness in a second independent sample of individuals with mTBI [19]. Moreover, unpublished data from that same study showed that individuals recovering from mTBI who underwent blue light exposure for 30 min each morning over six weeks also demonstrated a significant decline in depression scores from pre-to-post-treatment. Thus, light exposure treatment appears to be a promising approach to improve circadian functioning, alertness, and depression following concussion.

5. Considerations

Despite the many benefits of light therapy, is important to consider that light has many photobiological effects and is not completely innocuous. The glare from light can be aversive to some individuals and has been associated with headaches or eye strain [20], an important consideration for people recovering from an mTBI. Light can also lead to hypomanic episodes or increased agitation in some individuals with bipolar disorder, although this is not a universal finding [20]. There is also ongoing debate about the potential hazards associated with long-term blue light exposure. Shorter wavelength (i.e., blue) light may be associated with increased risk of photochemical damage to the retina. However, it is also true that blue light therapy is typically presented at much lower brightness levels and for shorter periods of time than broad spectrum white light, potentially reducing its overall hazard risk. Further research into the long-term effects of blue light exposure on eye health is warranted. Finally, while there is much evidence to suggest that low intensity blue wavelength light is equally effective to much brighter broad-spectrum white light for phase shifting circadian rhythms, it is not clear whether this same relationship also holds for improvements in depression. There is currently very limited data directly comparing blue versus white light exposure for improving mood, and more research into their comparability is needed.

6. Future directions

Light has a powerful effect on the circadian system, alertness, and mood. While its effects on SAD and non-seasonal depression are well established, light therapy has yet to be expanded to clinical practice to treat depression in neurologic disorders such as mTBI and other brain injuries. Preliminary evidence in those with concussion suggests that light therapy, particularly using blue wavelengths, may provide patients with a much-needed non-pharmacologic treatment option. Major issues that remain unresolved with regard to applying light therapy in mTBI and other disorders include determining the ideal time of day for administration, the most effective duration of exposure, and the optimal wavelength and illuminance to achieve maximal effect. Additionally, work is needed to identify and characterize individual differences in responsiveness to light treatments. All of these factors will need to be investigated and resolved through well-designed clinical trials if light exposure therapy is to become a mainstream clinical option for treating depression in concussion and other neurologic disorders.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

Research funding was provided by the following U.S. Army Medical Research Acquisition Activity grants: W81XWH-11-1-0056; W81WXH-14-1-0571; W81XWH-14-1-0570.