Bipolar disorder (BD) is a major mood disorder in which recurrent depression is twice as much as recurrent mania (35% vs. 14%). Bipolar depression is often complicated by episodic and chronic diseases, impaired psychosocial function, poor general health, decreased quality of life, and increased risk of suicide. The treatment of bipolar depression showed that only 38% of patients received antimanic medication, and 32.4% of patients received antidepressant medication.
Light therapy (LT) is a natural, low-risk intervention that has rapid, strong and sustained antidepressant effects on seasonal affective disorder (SAD), non-seasonal severe depression, and depression during pregnancy. Seasonal mood deterioration and atypical mood symptoms often described in bipolar disorder can highly predict positive responses to light therapy. In view of the limitations and complexity of drug treatment for bipolar disorder, bright light therapy and time therapy (referring to the treatment of patients based on a person’s daily, monthly, seasonal, or annual biological clock to maximize health benefits And reduce side effects) is expected to become a non-drug option for the treatment of bipolar disorder.
This article reviews the background and diagnosis of bipolar disorder, describes the potential circadian rhythms and neural mechanisms of strong light in the treatment of bipolar depression, and discusses the application of light therapy in clinical practice.
Bipolar Disorder: Background and Diagnosis
The lifetime prevalence of bipolar disorder is 1-2%, and the bipolar disorder spectrum disorder is 3.7-6.4%. Patients have persistent symptoms up to 47% of the time and a high risk of recurrence. The recurrence rates at 1 and 5 years are 40% and 87%, respectively. The cumulative impact of loss of function is huge. People with bipolar disorder cause up to 24 billion US dollars in losses to society every year. Bipolar disorder is characterized by mania or hypomania.
A major depressive episode accompanied by mania or hypomania is the most typical feature of BD-I, and it affects women and men the same. The subtypes of bipolar disorder also include type II (severe depressive episodes and hypomania), mixed episodes (simultaneous mania and depressive symptoms), and rapid cycling (4 or more episodes of opposite polarity in 1 year) , Is more common in women than men.
Patients with BD can have winter seasonal depression or SAD, usually onset in autumn or winter, relapse spontaneously in spring, and are classified as “with seasonal patterns” according to the DSM-5 standard. Patients with SAD and bipolar disorder are increasingly sensitive to environmental factors that alter the circadian rhythm and cause relapse. Patients may not necessarily increase the risk of seasonal mood changes, but they may still respond more strongly to circadian rhythm modifiers such as bright light. Strong light can regulate the circadian rhythm and improve mood symptoms through this mechanism or another thymosin effect.
Pathophysiology and Hypothetical Mechanism of Strong Light: Neurotransmission and Light
People are paying more and more attention to the effect of strong light on nerve function and the effect of light on serotonin neurotransmission. Broad-spectrum light therapy enhances serotonergic transmission in healthy volunteers and SAD patients. In contrast, the consumption of serotonin and dopamine precursors (tryptophan and catecholamines) quickly reversed the antidepressant effects of phototherapy, and led to recent SAD relief in patients with relapse, depression, and anhedonia.
The strong light treatment in winter significantly increased the serotonin activity of the anterior cingulate cortex, but it had no effect in autumn. Bright light serotonergic effects are also observed in the prefrontal cortex, and to a lesser extent in the midbrain. The serotoninergic system also distributes the projection of the midbrain suture to the SCN and provides regulatory input for the circadian rhythm. The activation of the serotonin 1A receptor produces a larger circadian rhythm phase change and inhibits the serotonin 1A activity (from the prolonged light pulse) associated with circadian inertia.
Although strong light can enhance the delivery of serotonin, compared with responders, those who do not respond to strong light and lack sleep at the same time show lower pre-treatment levels of serotonin. Therefore, in patients with severe serotonin deficiency, these time treatments may not provide an adequate response and may indicate other treatment modalities.
Variations in the serotonin transporter (SERT) gene are related to differences in serotonin signaling, risk of mood disorders, and treatment response. Compared with the long (L) allele, short (S) allele variants are associated with reduced serotonin signaling and increase the risk of SAD and atypical depression. In patients with bipolar disorder, carriers of the L allele have a significant predictive effect on the response to bright light. Asymptomatic carriers of the S allele received strong light daily for 3 weeks, under negative stimulation, the activity of the amygdala and medial prefrontal cortex (mPFC) decreased, which was related to mood improvement.
In summary, convincing pilot data findings indicate that SERT gene variants are regulators of phototherapy response, but further research is needed to replicate and validate these findings.
The Effect of Light Therapy on Nerve Function
To understand the neurological effects of light therapy, most studies have examined changes in cortical blood flow and functional activity. Functional activity studies have shown that cortical function has been significantly improved, mainly in the frontal and marginal areas, and there are some changes in the volume of the pituitary gland. Using the functional magnetic resonance imaging (fMRI) method, bright light can increase the brain response of healthy men and enhance the coupling between the prefrontal cortex and the amygdala. The effects of bright light also improved the function of the brainstem and subcortical areas of healthy patients.
The severity of winter depression symptoms is positively correlated with the volume of the pituitary gland, but not necessarily related to the reduction of symptoms after phototherapy. In patients who are susceptible to the negative effects of sleep loss, in the fMRI signals of the ventrolateral prefrontal cortex (PFC), dorsolateral PFC, and internal parietal groove, the blue signal is better than the green signal. Blue light particularly enhances the response to emotional stimuli in the temporal cortex and hippocampus that are not affected by green light. Improvements in mood symptoms indicate that bright light can cause changes in neurological function, but replication is needed to confirm their findings.
Neurological research began to distinguish between patients who responded to light therapy and patients who did not. Respondents measured by positron emission tomography (PET) showed that blood flow in the frontal cingulate cortex and thalamic cortex increased, and the connection between PFC, anterior cingulate cortex, and insula increased, which is the same as that after combined light therapy and sleep deprivation treatment The symptoms are alleviated. Those patients who did not respond to treatment showed lower connectivity at baseline and after treatment.
Patients with depression who responded to light therapy and sleep deprivation showed a greater increase in neurological excitability than those who did not. Compared with non-responders, the power of brain electrical signals, such as α, θ, and δ, of those who responded to light therapy was improved. Respondents to the combination therapy of sleep deprivation and morning light also showed increased blood flow in PFC, anterior cingulate gyrus, and lower corpus callosum, and decreased blood flow in the medial PFC and frontal pole at baseline.
In short, bright light may affect the neural pathways of depression. These data provide clues to the differential response of neurological function, which may be a predictor of treatment response, but further research is needed to determine its potential role in treatment planning.
How to Implement Light Therapy?
The important factors that determine the efficacy and side effects of strong light are closely related to time, intensity, duration, wavelength and distance from the light source. Most light sources are provided with an intensity of 10,000 lx (illuminance) within a distance of 12-13 inches. Although the treatment recommendation for SAD is 30 minutes a day and a morning dose of 10,000 lx, the early literature does not provide specific guidelines for BD.
A small pilot study used 2500 lx 2 h, 400 lx 2 h, 400 lx green light plus sleep deprivation, and 10000 lx 45-60 minutes twice a day to improve the depressive symptoms of BD every morning. Recent studies have shown that using 7000 lx broad-spectrum light for 30-60 minutes at noon has a certain effect. Although the best efficacy may be attributed to the blue wavelengths, broad-spectrum white light devices are preferable because they are most easily purchased by patients and have a definitive ophthalmic safety record.
It is recommended that patients receive anti-manic treatment before receiving light therapy, and receive regular monitoring and guidance from clinicians during the period of strong light therapy. The recommended device is a broad spectrum light lamp unit, which can emit 7000 lx, 4000 K blue rich white light, which meets the high standards of design and production. The preferred size is 12 inches x 14 inches, and provides a wide field of view lighting, lighting from above to avoid glare and maximize ultraviolet filtering. The optimal placement of the device is on a desktop stand 12 inches away from the eyes. During daily light treatment, the patient is required to face the light lamp instead of staring directly at the light lamp (to minimize discomfort).
For ease of use, it is recommended that patients use portable phototherapy lamps for treatment at home or at work every day. The initial treatment can be between 12 noon and 2:30 pm, 15 minutes a day. Thereafter, the duration of each week was increased by 15 minutes to reach the target dose of 60 minutes per day, or until the emotional symptoms were completely relieved.
Increasing the light dose depends on tolerance, side effects, and any hypo-irritability/mixed symptoms. Early remission (minimal to asymptomatic and normal function) is expected to require 4-6 weeks of treatment. For patients who have a partial or minimal response to the strong light at noon, the next step is to move the time of LT to the morning and titrate to a dose of 45-60 minutes/day.
Adverse Reactions of Light Therapy
Standard 7000-10000 lx, white fluorescent light box with ultraviolet light blocking, the risk of adverse consequences is minimal. Light is a unique and flexible treatment method. Its rapid onset and counteracting effects can be used for clinical effects. Adverse reactions usually disappear quickly after reducing the light dose. Side effects may include headaches, eye fatigue, agitation, nausea, and insomnia. In women, menstrual disorders and dysfunctional uterine bleeding have been reported. No eye effects were observed after 5 years.
During bright light therapy, patients who have experienced worsening depression, suicidal ideation, or sudden hypomania should contact their clinicians for proper clinical management immediately. Suicidal ideation may appear within 2 weeks after the start of mild treatment, more likely to appear in patients with inadequate antimania treatment, a history of rapid cycling, and before complete antidepressant effects.
Although we expect continued improvement after 6 weeks, there is currently no evidence on the durability of the response and how long patients should continue to use the light box. Given that patients with bipolar depression who stop maintenance treatment have twice the frequency of relapses (70% vs. 36%) of patients who continue treatment after 1 year, patients who have undergone bright light therapy can continue phototherapy at the same time to prevent relapse , And consider increasing the light dose or excessive light from noon to morning to enhance its response.
The findings so far indicate that morning light is the most widely tested form of light therapy of all mood disorders. Clinical trial reports show that bright light therapy at noon or morning and new time therapy interventions are effective for bipolar depression. The response mechanism may be related to the influence of the circadian rhythm system and other changes in nerve function. Researching an effective, visible physical intervention presents a major challenge for phototherapy researchers. Therefore, the successful completion of the research and the published report may be a very important contribution.
It is reasonable to use bright light to treat the depressive symptoms of bipolar disorder, but at the same time it requires anti-manic treatment and careful clinical monitoring of responsiveness, safety, and emotional polarity conversion. Whether to continue using strong light throughout the year to prevent recurrence (we don’t have data yet) or to stop treatment for individuals at risk of inducing mania requires a personalized plan and smart decisions.