Artificial light at night (ALAN) puts major pressure on the natural environment. There are five main ways of mitigating its biological impacts: avoidance of using ALAN, minimizing ALAN use, restoring or rehabilitating areas from ALAN, and offsetting the use of ALAN. Their potential effectiveness can be better understood through careful consideration of how organisms respond to light. Here we focus particularly on responses to altering recurring natural periods of light and darkness that affect the internal clock of organisms. All clocks are light sensitive and, depending on the photoreceptors of the organism, they show maximal responsiveness to different wavelengths, from UV to near infrared. Moreover, they show a high light-sensitivity, with a threshold at about intensities occurring during full moon or even less. This suggests that minimizing the use of ALAN through dimming of emissions and reducing the daily periods for which those lamps are in use may provide valuable benefits. However, if the biological effects of ALAN are to be widely reduced additional measures will need to be taken, including strengthening protection of the remaining dark spaces, reducing numbers of existing lights and restoring darkness in previously lit areas, and extensive shielding of those lights that are retained.

Daily and seasonal rhythms are programmed by neural circuits that anticipate predictable changes in the environment (i.e., temperature, food, predation). The time and duration of daily light exposure is a strategic cue used to predict changes in the environment that determine fitness and survival. Light is transduced by a specialized visual system that serves as an irradiance detector. These inputs are processed and encoded by the suprachiasmatic nucleus (SCN), which serves as the body’s daily clock and annual calendar. The SCN encodes time-of-day and photoperiod to regulate downstream systems via multiple routes (e.g., melatonin, cortisol, feeding, body temperature). A deeper understanding of SCN timekeeping circuits, photoperiodic encoding mechanisms, and light-driven cellular adaptations is imperative for understanding plasticity and pathology in multiple biological systems.

This review summarizes evidence on the modulation of functional responses mediated by activation of the MT1 and/or MT2 melatonin receptors by endogenous or exogenous melatonin. Selective MT1 inverse agonists, discovered by docking ultra large compound libraries to the MT1 crystal structure, decelerated the rate of re-entrainment of activity rhythms to a new dark onset. Surprisingly, these inverse agonists advanced circadian phase when given at subjective dusk mimicking melatonin through actions at MT1 receptors. The efficacy of environmental carbamates with structural similarity to melatonin interact with melatonin receptors and in turn advance circadian clock phase, as with melatonin. In summary, melatonin receptors are targets for drugs modulating circadian rhythms to yield therapeutic effects (i.e., synchronization), as well as for environmental chemicals that may induce harmful effects on human health due to actions on melatonin and on/off target receptors (e.g., serotonin) involved in signaling circadian time at inappropriate times of day.

Artificial light at night (ALAN) has become an increasingly important topic in epidemiology, as numerous studies have established a relationship between ALAN and adverse health effects, including cancer, obesity, depression, and sleep disruption. ALAN exposure measurements, however, vary from study to study and each measurement method has strengths and weaknesses. We review and summarize the pros and cons of different methods that have been used to quantify the light exposure in epidemiological settings, which include widely used remote sensing data, interview data, and individual-level wearable and handheld equipment. We also summarize the methodological approaches that have been used to analyze the spatial distribution of ALAN, as well as the relationships between ALAN and various adverse health outcomes. Finally, we highlight emerging technologies that could be used to measure the ALAN exposure for epidemiological studies, and how spatial analytical methods, such as geographically weighted regression and spatial autoregressive models can be leveraged to understand the spatial and temporal characteristics of ALAN and its mechanisms in regulating human physiology and behavior.

The physiological and mental impact of impaired fertility is recognized by the National Institute of Health, who identified fertility status as an overall marker of health. Reduced fertility is often linked with other physiological or genetic conditions, and precise alignment of physiological processes is essential to maintaining reproductive success. Reproductive function is closely linked with the circadian system, where studies in both humans and rodent research models have demonstrated that neuroendocrine mechanisms are sensitive to circadian disruption. Circadian rhythms throughout the body synchronize reproductive tissue function to the time of day by aligning hormone release with increased target tissue sensitivity to hormones. This chapter will review the current understanding of the neuroendocrine circuit regulating male and female fertility, and how light and genetic disruption of circadian rhythms impairs fertility.

Energy intake, utilization, and storage are critical to an animal’s health and fitness. The circadian clock organizes a variety of behavioral, physiological, and molecular processes to anticipate and optimize metabolic function. From behaviors such as the timing of feeding, to molecular interactions with the Clock gene, humans and other animals have evolved to coordinate metabolic processes to a 24-hour day. Thus, when circadian rhythms are disrupted or misaligned, an animal’s ability to anticipate and optimize metabolic processes is compromised. As discussed in this chapter, disruptions to circadian rhythmicity can result in adverse effects on body mass regulation and glucose homeostasis. Because these effects often present in parallel, this chapter organizes its discussion into two sections highlighting work from both clinical and preclinical animal studies. This approach allows one to appreciate the importance of circadian rhythmicity to metabolic wellbeing while introducing mechanistic explanations for how circadian disruption impacts body mass and glucose regulation.

The link between circadian rhythms and mental health is extensive. Circadian rhythm disruptions are commonly observed across many different psychiatric disorders and perturbation of the circadian system can precipitate or exacerbate psychiatric episodes. Together, this demonstrates a significant reciprocal relationship between circadian rhythm and mental health. Despite the extensive evidence linking circadian rhythms and mental health, studies are only beginning to uncover the neurobiological basis of this relationship. This chapter will provide an overview of the link between the circadian system and mental health. With the idea of a reciprocal relationship in mind, we will first discuss examples of circadian rhythm disruptions that impact mental health, such has exposure to artificial lighting, jetlag, and seasonal affective disorder. We will then discuss examples of psychiatric disorders and the circadian contribution to the pathophysiology of these disorders. Lastly, we will discuss strategies aimed at treating psychiatric disorders by targeting the circadian system.

A growing number of studies reveal that disruption of the endogenous, circadian (i.e., 24-hour) clock increases the risk for acquiring several diseases, including specific cancers. Significantly more work needs to be done to understand the molecular substrates involved in the mechanistic links between circadian clock disruption and cancer initiation and progression. Of particular complexity remains the contribution of the circadian clock in individual cells during the process of transformation (cancer initiation) versus its function in tumor-surrounding stroma and how this affects the process of tumor progression or metastasis. This chapter reviews some of the basic mechanisms understood to link circadian disruption and cancer at the level of gene expression and metabolism, while highlighting human studies supporting the association between circadian disruption and cancer incidence. In light of what is currently known, tremendous opportunites exist to use circadian approaches for future prevention and treatment strategies in the context of organ-specific cancer.

Typical blood pressure (BP) manifests a circadian rhythm, which is often disrupted in hypertension, type 2 diabetes mellitus, kidney disease, and sleep apnea. Disrupted circadian rhythm of BP is emerging as an index for detrimental cardiovascular outcomes. Time-restricted feeding or eating (TRF or TRE) involves restraining the daily food intake time window to 4–12 hours, mostly during the active phase. In addition to the well-documented numerous metabolic benefits of active phase-TRF, emerging evidence indicates profound effects of active phase-TRF on BP circadian rhythm. This chapter reviews the evidence and the underlying mechanisms via which the timing of food intake profoundly affects BP circadian rhythm and briefly discusses the potential of active phase-TRF as a novel behavioral intervention to reduce cardiometabolic risk.

In the last chapter we presented evidence tying intelligence differences among individuals to quantified details of brain structure and function. There were never doubts that intelligence is a function of the brain, so modern neuroimaging findings were not controversial in principle.