The first formal description of Seasonal Affective Disorder (SAD), the most well-known psychiatric condition associated with seasonality in humans, was introduced in the mid-1980s by Rosenthal, who described a group of 29 patients living in a temperate climate who experienced depressive episodes characterized by hypersomnia, hyperphagia, and weight gain in the fall or winter, and whose symptoms remitted by the next spring or summer.
SAD was incorporated into the Diagnostic and Statistical Manual (DSM) of Mental Disorders III-R when “seasonal pattern” was introduced as a specifier for Major Depression and Bipolar Disorders. Subsequent revision in DSM-IV described SAD as “a regular temporal relationship between the onset of Major Depressive Episodes in Bipolar I (BPI) or Bipolar II (BPII) Disorder or Major Depressive Disorder (MDD), recurrent, and a particular time of the year.”
Today, SAD, or MDD with seasonal pattern, is defined as recurrent episodes of major depression that meet the following criteria: at least two consecutive years where the onset and offset of depressive symptoms occur at characteristic times with no non-seasonal episodes, a temporal relationship between onset of symptoms and time of year, a temporal relationship between remission of symptoms and time of year, and an outnumbering of seasonal compared to non-seasonal episodes throughout the lifetime of the patient.
Pathophysiology of SAD
To date, the pathophysiology of SAD is unclear. Early research into the mechanism of SAD focused on day length or photoperiod. This hypothesis posited that shorter days in winter, possibly mediated by a longer duration of nocturnal melatonin secretion, leads to depressed mood in susceptible individuals. To date, there is little data to support this hypothesis. Furthermore, given that bright light in the evening has not been as effective as that given in the morning, it now seems unlikely that the photoperiod is the underlying pathological mechanism of SAD.
Although some animal studies have implicated a direct effect of light on the midbrain (Miller, Miller, Obermeyer, Behan, & Benca, 1999; Miller, Obermeyer, Behan, & Benca, 1998), the most prominent hypothesis driving human studies involves disruption of circadian rhythms. Research on the role of serotonin is also active.
A circadian rhythm refers to the approximately 24-hour cycle of physiological processes present in humans and other animals. This cycle is governed via clock gene expression by the suprachiasmatic nucleus (SCN), the master pacemaker located within the anterior hypothalamus. Though the SCN endogenously generates circadian oscillations, SCN endogenously generates circadian oscillations, and they need to be entrained to the 24-hour day by external cues. Light exposure is the most important synchronizing agent of endogenous circadian rhythms.
Downstream of the SCN, a collection of systemically active neurohumoral networks transduce circadian information to the rest of the body. For instance, via projections to the hypothalamus's paraventricular nucleus, the activation of the SCN leads to autonomic changes, including cardiovascular modulation, and together the central, peripheral, and autonomic nervous systems collaborate to affect systemic changes. Thus, the SCN receives information about the external day-night cycle directly through retinofugal pathways and indirectly through neuromodulatory signaling. Circadian information is then relayed systemically through neurohumoral networks.
The current primary hypothesis for the pathophysiology of SAD, known as the “phase-shift hypothesis,” posits that there is an optimal relationship in the alignment of the sleep-wake cycle and the endogenous circadian rhythm. During the fall and winter, as day length shortens, the circadian rhythm begins to drift later concerning clock time and the sleep-wake cycle. This phase delay is hypothesized to bring about mood symptoms. A pulse of morning bright light generates a circadian phase advance, which is thought to correct the discordance between sleep and circadian phase, thereby ameliorating depressive symptoms. However, the phase-shift hypothesis would predict that the amount of phase correction required for each patient would depend on an individual’s PAD, which has not yet been proven.
Several studies have also proposed that serotonin is implicated in the pathophysiology of SAD, as selective serotonin reuptake inhibitors (SSRIs) appear to be effective in the treatment of SAD. Supporting this hypothesis, one study used Positron Emission Tomography (PET) imaging to look at binding probability at synaptic serotonin transporters in 88 normal individuals living in the temperate climate of Toronto, Canada (Praschak-Rieder, Willeit, Wilson, Houle, & Meyer, 2008). The binding probability was increased during fall and winter compared to warmer months, thus eliciting an inverse correlation between binding potential and sunlight durationsunlight duration. Of note, the largest difference in transporter binding was found in the mesencephalon, a finding consistent with animal studies demonstrating the importance of direct effects of light to the midbrain on behavior. If increased transporter activity indicated greater reuptake of serotonin during the fall/winter, and if this resulted in a lower density of cleft serotonin, then the seasonal variation in transporter activity (i.e., higher transporter efficiency in the winter) would seem to leave susceptible individuals particularly prone to mood symptoms during the darker seasons. Moreover, following BLT and during periods of remission in the summer months, the synaptic transporter activity was shown to be reduced to control levels in these patients.
BLT has also been investigated to a lesser extent in eating disorders. Because binge eating episodes have been observed to increase in fall and winter in some patients, BLT has been examined as a treatment modality for anorexia nervosa (AN) and bulimia nervosa (BN). Thus, BLT's effects on patients with eating disorders remain enigmatic. Additional studies, including larger, randomized, blinded, and controlled trials, are needed to elucidate further the role of BLT in treating this patient population. Further research might also determine whether BLT would be a useful treatment in Binge-Eating Disorder, a diagnosis new to DSM-5.
Additionally, BLT has been studied in the context of adult Attention-Deficit/Hyperactivity Disorder (ADHD), where, in addition to normal ADHD symptoms, patients often have depressed mood and difficulties falling asleep, awakening on time, and maintaining arousal (Brown & McMullen, 2001). These symptoms are indicative of a possible delay in the circadian rhythm. A case report of symptom improvement following BLT in a child with ADHD who displayed signs of delayed sleep phase also supports the idea that BLT may be useful in treating symptoms of ADHD (Gruber, Grizenko, & Joober, 2007). Whether the pathways that subserve the improvement of mood symptoms in response to BLT are the same pathways that underlie the seemingly beneficial effects of BLT in ADHD remains to be studied. While these results are promising, further studies, preferably in randomized, blinded, and controlled studies will need to be performed.
A significant immediate reduction of depression scores with light treatment can be identified after 20 minutes and reaches the maximum at 40 minutes, with no additional benefit at 60 minutes. The rate of change is steepest during the first 20 minutes of light as compared with longer intervals. Comparing the clinical impact of these durations of administration may yield different results when measured after several daily sessions. The overnight effect on circadian rhythms and sleep was not assessed in our study and is thought to impact mood regulation in SAD. Larger, prospective, controlled, and hypothesis-driven studies in more naturalistic conditions would be desirable to replicate our study results and our study results and analyze the temporal dynamic of the persistence of the immediate mood-improvement effects. Besides, in larger samples, one could define early responders and nonresponders, analyze genetic (e.g., melanopsin related genes), demographic (children, adolescents, adults, elderly, gender), physiological (e.g., pupillary responses), and clinical (e.g., abundant atypical symptoms) predictors for early response. If proven effective and efficacious, shorter exposures to bright light could become a feasible and broadly employed intervention for immediate mood improvement as an early step on the road toward full antidepressant response and remission.