Feeling a bit depressed recently? Is it because you play too much on your phone before going to bed?

Author: Wang Bo (Institute of Biophysics, Chinese Academy of Sciences)

The article comes from the Science Academy official account (ID: kexuedayuan)

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Many people believe that the development of AI will eventually lead to humans being controlled by machines. In fact, there is no need to worry so much, because we are now controlled by some machines that are only the size of a palm, flat and ugly, and can't even walk! They are smartphones (hereinafter referred to as "mobile phones")! !

Playing with mobile phone while eating (Photo source: People's Daily Online)

Playing with mobile phone before going to bed (Photo source: People's Daily Online)

However, we often “feel good for a while by checking our phones before going to bed”, but we don’t seem to “keep checking and feel good all the time”, why is that?

"I play with my phone every day before going to bed, and I am depressed"

A study published in the American journal Sleep by researchers from South Korea's Chongshin Women's University showed that playing with mobile phones before bedtime affects mental health. People who delay sleep due to playing with mobile phones are more likely to suffer from depression, anxiety and insomnia.

The study surveyed 160 people aged between 20 and 30, who spent five times more time playing with their phones before bed than the average person. The results showed that playing with the phone for a long time before bedtime can have a negative impact on health and psychology, increasing the risk of depression by 20% and anxiety by 14%. Delaying bedtime can increase the risk of insomnia by 41%, and the risk of insomnia caused by playing with the phone before bedtime is even higher, reaching 82% [1].

What factors lead to such serious mental health problems? Mr. "Sleeping Late" said that he would never bear the blame alone, and the light emitted by the mobile phone in the dark night is also a "murderer".

Recent studies on the neural circuits that regulate emotions through light have shown that changes in the light environment not only affect the circadian rhythm of organisms, but also significantly modulate mental states. A study published in Cell in 2018 showed that long-term fragmented light and dark stimulation may induce negative emotions [2]. In contrast, daylight can often positively regulate human emotions [3]. During the day and night, light has completely opposite effects on emotions, and the neural mechanism behind this has always been an unsolved mystery. It is still unknown whether it is light or rhythm disturbance that affects emotions.

On June 1 this year, Professor Xue Tian from the University of Science and Technology of China and Zhao Huan's team from Hefei University published their latest research results online in Nature Neuroscience titled "A circadian rhythm-gated subcortical pathway for nighttime-light-induced depressive-like behaviors in mice". The results describe the structure and function of the neural circuits that mediate the depressive-like phenotype induced by abnormal nighttime light, and prove that it is the abnormal nighttime light rather than the disorder of rhythm or sleep that causes depressive-like behavior. This is the first time to explain the internal mechanism of the opposite emotional effects of light during the day and at night. In short, the increase in blue light exposure at night affects specific neural circuits in the brain, leading to the emergence of depressive symptoms [4].

This study is the first to comprehensively explain the circuit basis and rhythmic gating mechanism of night light-induced negative emotions, and provides neuroscientific evidence based on model animal studies for the above findings and the mystery of the impact of light on emotions. "Blue light" has become a major suspect in causing depression.

"Blue light" is widely present in the spectrum components emitted by natural light, incandescent lamps, fluorescent lamps, energy-saving lamps, and various light sources such as LCDs and LEDs. Although the state has relevant regulations on the composition of the spectrum components emitted by electronic products, such as display screens and mobile phone screens, to avoid the adverse effects of high-energy blue-violet light on our eyes, using electronic screens for a long time at night will still cause the eyes to be exposed to concentrated "blue light", which is not much.

Depressed mice under blue light

The research subjects of Professor Xue Tian and Zhao Huan's team in this work are mice. Although the day and night preferences of mice are opposite to those of humans, their behavior is also affected by daily light changes and circadian rhythms. The research team constructed a light interference (light at night, LAN) model for mice, that is, in the circadian rhythm of mice (8:00-20:00 during the day; 20:00-8:00+1 at night), they selected 2 hours between 21:00-23:00 every night and irradiated them with blue light for three consecutive weeks. The results showed that the circadian rhythm of mice was not changed, but some unusual behaviors gradually appeared.

For example, when forced to swim, it gave up and showed no signs of moving; when faced with sugar water, its preference for sugar water decreased - happy water was no longer happy! Because these behaviors are similar to human depression, the researchers defined them as depression-like behaviors. Not only that, after the blue light exposure was cancelled every night, the mice did not recover immediately, and the depression-like behavior continued for up to 3 weeks.

(Image source: Nature Neuroscience, 2020)

How does light exposure at night lead to depression?

Light affects various physiological functions of mammals, including mood. On the one hand, many studies have shown that moderate exposure to sunlight during the day can improve mood, and the use of "light therapy" to supplement light can relieve symptoms of depression. On the other hand, excessive light from light pollution or electronic devices at night is considered to have the risk of causing depressive symptoms. Previous studies have shown that blue light at night can have a negative impact on mood.

Xue Tian and Zhao Huan's team of researchers used neural tracing tools to discover a special "ipRGCs-dpHb-NAc" ("autonomous photoreceptor ganglion cells-dorsolateral region of the habenular nucleus-nucleus accumbens") neural circuit in the brain. They inferred that the process of emotion regulation in this circuit may be the reason why blue light at night makes mice depressed.

The starting point of this neural circuit is a special type of cell on the retina - intrinsically photosensitive retinal ganglion cells (ipRGCs), a type of ganglion cell with photosensitivity discovered twenty years ago, which updated our previous traditional understanding of the signal transduction function of (ordinary) ganglion cells.

The second stop of the loop is the lateral habenular region (pHb), which is divided into the dorsolateral region (dpHb) and the ventrolateral region (vpHb). The lateral habenular region is often called the "anti-reward center" of the brain. It mediates many negative emotions and is the headquarters that causes our bad mood.

The end point of the loop is the nucleus accumbens (NAc), which receives signals from the dorsolateral part of the habenular nucleus. The nucleus accumbens is the second most important dopamine system in the brain. It is also the most studied and most concerned nucleus related to addiction, reward and punishment behaviors. It has a great relationship with the formation of pleasure, which is equivalent to the "Happy Valley" in the brain. It is also involved in the formation of depression.

So, how does "blue light" act on the brain through the autonomous photosensitive ganglion cells on the retina to affect the emotions of mice?

Generally, the light-sensitive cells on the retina that we are familiar with are cones and rods. Cones, as their name suggests, require stronger light and can sense red, green and blue light (there are three different types of cones, each with a corresponding photosensitive pigment), but they have "night blindness"; rods are slender and "color blind", but they can maintain high sensitivity in dim light and provide "night vision" capabilities. When we open our eyes in the middle of the night, we can see the shape and outline of furniture but cannot distinguish its color, which is the result of almost only rods working.

Blue is cone cells, which are good at distinguishing colors; yellow is rod cells, which are good at "dark vision" (Image source: Zhihu)

These two types of receptor cells receive light and generate electrical signals, which are transmitted to bipolar cells, and then to ganglion cells; the axons of the ganglion cells form optic nerve fibers, gather at the optic tract (optic nerve) papilla, exit the eyeball through the cribriform plate, become the optic nerve, and project to the visual cortex of the brain through the lateral geniculate body, forming the entire visual pathway.

Schematic diagram of the multi-layered cell structure on the retina (Image source: Ophthalmology)

Visual pathway (Image source: "Principles of Neural Science 5th Edition")

Autonomous photoreceptor ganglion cells were discovered at the end of the last century to express the photopigment melanopsin and have the ability to sense light. In rodents, autonomous photoreceptor ganglion cells are directly involved in non-imaging and imaging visual processes, including pupil light reflex, circadian rhythm regulation, color vision, and spatial perception. Chellappa published a paper in the Proceedings of the National Academy of Sciences, pointing out that "the discovery of autonomous photoreceptor ganglion cells is one of the most significant discoveries in neuroscience in the past decade. Its discovery has led to a completely revolutionary understanding of the function of the eye [5].

Fluorescence staining of ipRGCs ganglion cells (Image source: Courtesy Elliott Milner, Ph.D)

Using transgenic mice lacking rods, cones and autonomous photoreceptor ganglion cells, Xue Tian and Zhao Huan's team found that autonomous photoreceptor ganglion cells also play a sufficient and necessary role in the process of depression induced by night light interference.

When the autonomous photoreceptor ganglion cells are activated by a specific wavelength of blue light (~480nm), they transmit signals to the lateral limbic region of the habenula; the nerve cells in the dorsolateral limbic region of the habenula then transmit the signals to the nucleus accumbens (NAc), and the ventral region projects to the medial prefrontal cortex (mPFC). These brain regions are closely related to depressive symptoms. Among them, the overactivity of the lateral habenula can induce depressive-like behavior; the nucleus accumbens is also involved in the formation of depression; and the prefrontal cortex is closely related to emotions and high-level cognition.

The "ipRGCs- dpHb-NAc" neural pathway that causes depressive-like behavior when light is increased at night. The "dpHb-NAc" projection plays a core role in the negative emotions induced by nighttime light disturbance (Image source: Nature Neuroscience, 2020)

When researchers blocked the neural connection between the lateral habenula and the nucleus accumbens in the mouse brain, they could prevent the mice from developing depressive-like behaviors induced by night light exposure; at the same time, using optogenetics to activate the projection of autonomous photoreceptor ganglion cells to the lateral habenula could induce depressive-like behaviors in mice. These results fully verified that the lateral habenula is an important circuit node that mediates the interference of night light.

The researchers further inhibited the input of the lateral habenula to the prefrontal cortex and nucleus accumbens through adeno-associated virus tools (AAV, a safe, long-lasting, efficient and highly specific gene manipulation tool). The results confirmed that only by inhibiting the projection of the "dorsolateral habenula limbic area-nucleus accumbens" would the effect of night light interference be affected. At the same time, directly activating the projection of the "dorsolateral habenula limbic area-nucleus accumbens" at a specific time at night for three weeks can induce depressive-like performance without relying on night light. These evidences reveal the core role of the projection of the "dorsolateral habenula limbic area-nucleus accumbens" in the negative emotions induced by night light interference, which is a veritable "depression pathway".

Upper figure: "dpHb-NAc" conduction blockade affects the depression-inducing effect of LAN; Lower figure: Direct activation of the "dpHb-NAc" pathway can induce depressive-like behavior in mice without LAN (Image source: Nature Neuroscience, 2020)

Finally, in order to further explore the mechanism by which light regulates emotions differently during the day or at night. Through single-cell patch clamp and in vivo fiber optic recording, the researchers found that neurons in the dorsal region of the lateral habenula projecting to the nucleus accumbens are more excitable at night than during the day, and are more likely to fire action potentials; while neurons in the ventral region of the lateral habenula projecting to the prefrontal cortex do not have a similar phenomenon. The results show that neurons in the dorsal region of the lateral habenula projecting to the nucleus accumbens act as a valve controlled by the circadian rhythm, which only opens at night, allowing night light signals to affect the "Happy Valley" nucleus accumbens through the "depression pathway", thereby inducing negative emotions. This may explain why daytime light exposure does not lead to changes in emotional behavior.

The researchers further speculated that this circuit, by inducing negative emotions, may prompt animals to avoid unnecessary light during the night period of their circadian rhythm, helping to avoid enemies or prevent their own biological rhythms from being disturbed, especially during light transition periods, such as dusk or dawn. However, in the post-industrial era, exposure to light stimulation at night is becoming increasingly unavoidable. Therefore, this functional circuit that has evolved for protective purposes may be "hijacked" by artificial light at night, inducing negative emotions in humans.

The potential negative effects of nighttime light exposure on mental health need to be addressed

Of course, this study does not mean that "playing with mobile phones before going to bed will cause depression". There are many factors that lead to depression, and no one factor works alone.

In the discussion of the paper, the researchers also pointed out that it is necessary to be cautious whether this finding can be extrapolated to humans. After all, mouse experiments have their limitations. For example, mice themselves hate light, so their negative emotions towards light may be extra strong. Moreover, behaviors such as not preferring sugar water may not be the same as real depression in humans.

However, the authors conclude that identifying the neural pathways in the brain that night light affects is the first step in understanding the effects of increased light exposure at night on mood. If light activates the same neural circuits in humans, these results may help explain how excessive night light exposure affects humans and why it is associated with depressive symptoms.

(Photo source: veer photo gallery)

With the advancement of industry and technology, nighttime lighting is becoming more and more common. Many people live under the neon lights of the "city that never sleeps". When the landscape lights go out late at night, they return home and continue to be accompanied by the blue light emitted by electronic devices. However, humans have adapted to the changes in light during the day and night during millions of years of evolution. When there is excessive light at night, our health and mood may be quietly affected negatively. This includes the role of mobile phone blue light.

Checking your phone before going to bed has gradually become a routine activity for most of us before going to bed, and the execution rate has exceeded brushing your teeth before going to bed. There are indeed many hidden dangers behind this habit, such as impaired vision, irregular work and rest, poor skin, numbness of fingers, chronic neck strain, and may lead to depression!

So, how can we avoid the harm of looking at our phones before going to bed? How can we still enjoy the delicious food, beautiful scenery and happy exercise? Only by putting down your phone and having a good sleep!

References:

[1] Chung SJ, An H & Suh S. What do people do before going to bed? A study of bedtime procrastination using time use surveys. Sleep. 2019; 43 (4): zsz267. https://doi.org/10.1093/sleep/zsz267

[2] Fernandez DC, Fogerson PM, Ospri LL, Thomsen MB, Layne RM, Severin D, Zhan J, Singer JH, Kirkwood A, Zhao H, Berson DM & Hattar S. Light Affects Mood and Learning through Distinct Retina-Brain Pathways. Cell. 2018; 175 (1): 71-84.e18. doi.org/10.1016/j.cell.2018.08.004.

[3] Huang C, Ruff DA, Pyle R, Rosenbaum R, Cohen MR, Doiron B. Circuit Models of Low-Dimensional Shared Variability in Cortical Networks. Neuron. 2019; 101(2): 337-348.e4. doi:10.1016/j.neuron.2018.11.034.

[4] An K, Zhao H, Miao Y et al. A circadian rhythm-gated subcortical pathway for nighttime-light-induced depressive-like behaviors in mice. Nat Neurosci. 2020; 23: 869–880. doi.org/10.1038/s41593-020-0640-8.

[5] Chellappa SL, Ly JQM, Meyer C, Balteau E, Degueldre C, Luxen A, Phillips C, Cooper HM & Vandewalle G. Photic memory for executive brain responses. PNAS. 2014; 111 (16): 6087-6091. doi.org/10.1073/pnas.1320005111.