Imaging Individual Differences in the Response of the Human Suprachiasmatic Area to Light

Circadian disruption is associated with poor health outcomes, including sleep and mood disorders. The suprachiasmatic nucleus (SCN) of the anterior hypothalamus acts as the master biological clock in mammals, regulating circadian rhythms throughout the body. The clock is synchronized to the day/night cycle via retinal light exposure. The BOLD-fMRI response of the human suprachiasmatic area to light has been shown to be greater in the night than in the day, consistent with the known sensitivity of the clock to light at night. Whether the BOLD-fMRI response of the human suprachiasmatic area to light is related to a functional outcome has not been demonstrated. In a pilot study (n = 10), we investigated suprachiasmatic area activation in response to light in a 30 s block-paradigm of lights on (100 lux) and lights off (< 1 lux) using the BOLD-fMRI response, compared to each participant's melatonin suppression response to moderate indoor light (100 lux). We found a significant correlation between activation in the suprachiasmatic area in response to light in the scanner and melatonin suppression, with increased melatonin suppression being associated with increased suprachiasmatic area activation in response to the same light level. These preliminary findings are a first step toward using imaging techniques to measure individual differences in circadian light sensitivity, a measure that may have clinical relevance in understanding vulnerability in disorders that are influenced by circadian disruption

Genetic and clinical analyses of psychosis spectrum symptoms in a large multiethnic youth cohort reveal significant link with ADHD

Psychotic symptoms are not only an important feature of severe neuropsychiatric disorders, but are also common in the general population, especially in youth. The genetic etiology of psychosis symptoms in youth remains poorly understood. To characterize genetic risk for psychosis spectrum symptoms (PS), we leverage a community-based multiethnic sample of children and adolescents aged 8–22 years, the Philadelphia Ne

Accuracy of the GENEActiv device for measuring light exposure in sleep and circadian research

Light is a variable of key interest in circadian rhythms research, commonly measured using wrist-worn sensors. The GENEActiv Original is a cost-effective and practical option for assessing light in ambulatory settings. With increasing research on health and well-being incorporating sleep and circadian factors, the validity of wearable devices for assessing light environments needs to be evaluated. In this study, we tested the accuracy of the GENEActiv Original devices (n = 10) for recording light under a range of ecologically relevant lighting conditions, including LED, fluorescent, infrared, and outdoor lighting. The GENEActiv output had a strong linear relationship with photopic illuminance. However, the devices consistently under-reported photopic illuminance, especially below 100 lux. Accuracy below 100 lux depended on the light source, with lower accuracy and higher variability under fluorescent lighting. The device’s accuracy was also tested using light sources of varying spectral composition, which indicated that the device tends to under-report photopic illuminance for green light sources and over-report for red light sources. Furthermore, measures of photopic illuminance were impacted by infrared light exposure. We conclude that the GENEActiv Original is suitable for mapping light patterns within an individual context, and can reasonably differentiate indoor vs. outdoor lighting, though the accuracy is variable at low light conditions. Given the human circadian system’s high sensitivity to light levels below 100 lux, if using the GENEActiv Original, we recommend also collecting light source data to better understand the impact on the circadian system, especially where participants spend prolonged periods in dim lighting

Imaging Individual Differences in the Response of the Human Suprachiasmatic Area to Light

Circadian disruption is associated with poor health outcomes, including sleep and mood disorders. The suprachiasmatic nucleus (SCN) of the anterior hypothalamus acts as the master biological clock in mammals, regulating circadian rhythms throughout the body. The clock is synchronized to the day/night cycle via retinal light exposure. The BOLD-fMRI response of the human suprachiasmatic area to light has been shown to be greater in the night than in the day, consistent with the known sensitivity of the clock to light at night. Whether the BOLD-fMRI response of the human suprachiasmatic area to light is related to a functional outcome has not been demonstrated. In a pilot study (n = 10), we investigated suprachiasmatic area activation in response to light in a 30 s block-paradigm of lights on (100 lux) and lights off (< 1 lux) using the BOLD-fMRI response, compared to each participant's melatonin suppression response to moderate indoor light (100 lux). We found a significant correlation between activation in the suprachiasmatic area in response to light in the scanner and melatonin suppression, with increased melatonin suppression being associated with increased suprachiasmatic area activation in response to the same light level. These preliminary findings are a first step toward using imaging techniques to measure individual differences in circadian light sensitivity, a measure that may have clinical relevance in understanding vulnerability in disorders that are influenced by circadian disruption

Afraid of the dark : Light acutely suppresses activity in the human amygdala

Light improves mood. The amygdala plays a critical role in regulating emotion, including fear-related responses. In rodents the amygdala receives direct light input from the retina, and light may play a role in fear-related learning. A direct effect of light on the amygdala represents a plausible mechanism of action for light’s mood-elevating effects in humans. However, the effect of light on activity in the amygdala in humans is not well understood. We examined the effect of passive dim-to-moderate white light exposure on activation of the amygdala in healthy young adults using the BOLD fMRI response (3T Siemens scanner; n = 23). Participants were exposed to alternating 30s blocks of light (10 lux or 100 lux) and dark (<1 lux), with each light intensity being presented separately. Light, compared with dark, suppressed activity in the amygdala. Moderate light exposure resulted in greater suppression of amygdala activity than dim light. Furthermore, functional connectivity between the amygdala and ventro-medial prefrontal cortex was enhanced during light relative to dark. These effects may contribute to light’s mood-elevating effects, via a reduction in negative, fear-related affect and enhanced processing of negative emotion

The pupillary light reflex distinguishes between circadian and non-circadian delayed sleep phase disorder (DSPD) phenotypes in young adults.

This study investigated the utility of the pupillary light reflex as a method of differentiating DSPD patients with delayed melatonin timing relative to desired/required sleep time (circadian type) and those with non-delayed melatonin timing (non-circadian type). All participants were young adults, with a total of 14 circadian DSPD patients (M = 28.14, SD = 5.26), 12 non-circadian DSPD patients (M = 29.42, SD = 11.51) and 51 healthy controls (M = 21.47 SD = 3.16) completing the protocol. All participants were free of central nervous system acting medications and abstained from caffeine and alcohol on the day of the assessment. Two pupillary light reflex measurements were completed by each participant, one with a 1s dim (~10 lux) light exposure, and one with a 1s bright (~1500 lux) light exposure. Circadian DSPD patients showed a significantly faster pupillary light reflex than both non-circadian DSPD patients and healthy controls. Non-circadian patients and healthy controls did not differ significantly. Receiver operating characteristic curves were generated to determine the utility of mean and maximum constriction velocity in differentiating the two DSPD phenotypes, and these demonstrated high levels of sensitivity (69.23--100%) and specificity (66.67-91.67%) at their optimal cut offs. The strongest predictor of DSPD phenotype was the mean constriction velocity to bright light (AUC = 0.87). These results support the potential for the pupillary light reflex to clinically differentiate between DSPD patients with normal vs. delayed circadian timing relative to desired bedtime, without the need for costly and time-consuming circadian assessments

Genetic and clinical analyses of psychosis spectrum symptoms in a large multiethnic youth cohort reveal significant link with ADHD.

Psychotic symptoms are not only an important feature of severe neuropsychiatric disorders, but are also common in the general population, especially in youth. The genetic etiology of psychosis symptoms in youth remains poorly understood. To characterize genetic risk for psychosis spectrum symptoms (PS), we leverage a community-based multiethnic sample of children and adolescents aged 8-22 years, the Philadelphia Neurodevelopmental Cohort (n = 7225, 20% PS). Using an elastic net regression model, we aim to classify PS status using polygenic scores (PGS) based on a range of heritable psychiatric and brain-related traits in a multi-PGS model. We also perform univariate PGS associations and evaluate age-specific effects. The multi-PGS analyses do not improve prediction of PS status over univariate models, but reveal that the attention deficit hyperactivity disorder (ADHD) PGS is robustly and uniquely associated with PS (OR 1.12 (1.05, 1.18) P = 0.0003). This association is driven by subjects of European ancestry (OR = 1.23 (1.14, 1.34), P = 4.15 × 10-7) but is not observed in African American subjects (P = 0.65). We find a significant interaction of ADHD PGS with age (P = 0.01), with a stronger association in younger children. The association is independent of phenotypic overlap between ADHD and PS, not indirectly driven by substance use or childhood trauma, and appears to be specific to PS rather than reflecting general psychopathology in youth. In an independent sample, we replicate an increased ADHD PGS in 328 youth at clinical high risk for psychosis, compared to 216 unaffected controls (OR 1.06, CI(1.01, 1.11), P = 0.02). Our findings suggest that PS in youth may reflect a different genetic etiology than psychotic symptoms in adulthood, one more akin to ADHD, and shed light on how genetic risk can be investigated across early disease trajectories

Genetic and clinical analyses of psychosis spectrum symptoms in a large multiethnic youth cohort reveal significant link with ADHD.

Psychotic symptoms are not only an important feature of severe neuropsychiatric disorders, but are also common in the general population, especially in youth. The genetic etiology of psychosis symptoms in youth remains poorly understood. To characterize genetic risk for psychosis spectrum symptoms (PS), we leverage a community-based multiethnic sample of children and adolescents aged 8-22 years, the Philadelphia Neurodevelopmental Cohort (n = 7225, 20% PS). Using an elastic net regression model, we aim to classify PS status using polygenic scores (PGS) based on a range of heritable psychiatric and brain-related traits in a multi-PGS model. We also perform univariate PGS associations and evaluate age-specific effects. The multi-PGS analyses do not improve prediction of PS status over univariate models, but reveal that the attention deficit hyperactivity disorder (ADHD) PGS is robustly and uniquely associated with PS (OR 1.12 (1.05, 1.18) P = 0.0003). This association is driven by subjects of European ancestry (OR = 1.23 (1.14, 1.34), P = 4.15 × 10-7) but is not observed in African American subjects (P = 0.65). We find a significant interaction of ADHD PGS with age (P = 0.01), with a stronger association in younger children. The association is independent of phenotypic overlap between ADHD and PS, not indirectly driven by substance use or childhood trauma, and appears to be specific to PS rather than reflecting general psychopathology in youth. In an independent sample, we replicate an increased ADHD PGS in 328 youth at clinical high risk for psychosis, compared to 216 unaffected controls (OR 1.06, CI(1.01, 1.11), P = 0.02). Our findings suggest that PS in youth may reflect a different genetic etiology than psychotic symptoms in adulthood, one more akin to ADHD, and shed light on how genetic risk can be investigated across early disease trajectories