Dr. Yu-Shiuan Lin
PhD, Psychologist
My research interest is using neuroimaging methods to investigate the impacts of daily caffeine intake and acute caffeine withdrawal on cerebral structures, perfusion, and neurocognitive functions. In particular, I am using neurobehavioral model to examine in the caffeine effects on striatal dopamine signaling and functions through the adenosinergic modulation. In addition, I also looked into the potential impacts of daily caffeine intake on the pharmacokinetics of caffeine and its metabolites.
Publications
2022
Lin, Y. -S.; Weibel, J.; Landolt, H. -P.; Santini, F; Garbazza, C; Kistler, J; Rehm, S; Rentsch, K; Borgwardt, S; Cajochen, C; Reichert, C. F.
Time to recover from daily caffeine intake Journal Article
In: Front Nutr., vol. 8, no. 787225, 2022.
@article{Lin2022,
title = {Time to recover from daily caffeine intake},
author = {Y.-S. Lin and J. Weibel and H.-P. Landolt and F Santini and C Garbazza and J Kistler and S Rehm and K Rentsch and S Borgwardt and C Cajochen and C. F. Reichert},
url = {https://www.frontiersin.org/articles/10.3389/fnut.2021.787225/full},
doi = {10.3389/fnut.2021.787225. },
year = {2022},
date = {2022-02-02},
journal = {Front Nutr.},
volume = {8},
number = {787225},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2021
Weibel, J.; Lin, Y. -S.; Landolt, H. -P.; Berthomier, C.; Brandenwinder, M.; Kistler, J.; Rehm, S.; Rentsch, K.; Meyer, M.; Borgwardt, S.; Cajochen, C.; Reichert, C. F.
Regular caffeine intake delays REM sleep promotion and attenuates sleep quality in healthy men Journal Article
In: Journal of Biological Rhythms, 2021.
@article{Weibel2021b,
title = {Regular caffeine intake delays REM sleep promotion and attenuates sleep quality in healthy men},
author = {J. Weibel and Y.-S. Lin and H.-P. Landolt and C. Berthomier and M. Brandenwinder and J. Kistler and S. Rehm and K. Rentsch and M. Meyer and S. Borgwardt and C. Cajochen and C. F. Reichert },
url = {https://journals.sagepub.com/doi/pdf/10.1177/07487304211013995},
doi = {10.1177/07487304211013995},
year = {2021},
date = {2021-05-23},
journal = {Journal of Biological Rhythms},
abstract = {Acute caffeine intake can attenuate homeostatic sleep pressure and worsen sleep quality. Caffeine intake—particularly in high doses and close to bedtime—may also affect circadian-regulated rapid eye movement (REM) sleep promotion, an important determinant of subjective sleep quality. However, it is not known whether such changes persist under chronic caffeine consumption during daytime. Twenty male caffeine consumers (26.4 ± 4 years old, habitual caffeine intake 478.1 ± 102.8 mg/day) participated in a double-blind crossover study. Each volunteer completed a caffeine (3 × 150 mg caffeine daily for 10 days), a withdrawal (3 × 150 mg caffeine for 8 days then placebo), and a placebo condition. After 10 days of controlled intake and a fixed sleep-wake cycle, we recorded electroencephalography for 8 h starting 5 h after habitual bedtime (i.e., start on average at 04:22 h which is around the peak of circadian REM sleep promotion). A 60-min evening nap preceded each sleep episode and reduced high sleep pres-sure levels. While total sleep time and sleep architecture did not significantly differ between the three conditions, REM sleep latency was longer after daily caffeine intake compared with both placebo and withdrawal. Moreover, the accumulation of REM sleep proportion was delayed, and volunteers reported more difficulties with awakening after sleep and feeling more tired upon wake-up in the caffeine condition compared with placebo. Our data indicate that besides acute intake, also regular daytime caffeine intake affects REM sleep regulation in men, such that it delays circadian REM sleep promotion when compared with placebo. Moreover, the observed caffeine-induced deterioration in the quality of awakening may suggest a potential motive to reinstate caffeine intake after sleep.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Acute caffeine intake can attenuate homeostatic sleep pressure and worsen sleep quality. Caffeine intake—particularly in high doses and close to bedtime—may also affect circadian-regulated rapid eye movement (REM) sleep promotion, an important determinant of subjective sleep quality. However, it is not known whether such changes persist under chronic caffeine consumption during daytime. Twenty male caffeine consumers (26.4 ± 4 years old, habitual caffeine intake 478.1 ± 102.8 mg/day) participated in a double-blind crossover study. Each volunteer completed a caffeine (3 × 150 mg caffeine daily for 10 days), a withdrawal (3 × 150 mg caffeine for 8 days then placebo), and a placebo condition. After 10 days of controlled intake and a fixed sleep-wake cycle, we recorded electroencephalography for 8 h starting 5 h after habitual bedtime (i.e., start on average at 04:22 h which is around the peak of circadian REM sleep promotion). A 60-min evening nap preceded each sleep episode and reduced high sleep pres-sure levels. While total sleep time and sleep architecture did not significantly differ between the three conditions, REM sleep latency was longer after daily caffeine intake compared with both placebo and withdrawal. Moreover, the accumulation of REM sleep proportion was delayed, and volunteers reported more difficulties with awakening after sleep and feeling more tired upon wake-up in the caffeine condition compared with placebo. Our data indicate that besides acute intake, also regular daytime caffeine intake affects REM sleep regulation in men, such that it delays circadian REM sleep promotion when compared with placebo. Moreover, the observed caffeine-induced deterioration in the quality of awakening may suggest a potential motive to reinstate caffeine intake after sleep.
Lin, Y. -S.; Weibel, J; Landolt, H. -P.; Santini, F; Slawik, H; Borgwardt, S; Cajochen, C; Reichert, C. F.
Working Memory Performance after Daily Caffeine Intake: Compromised Performance and Reduced Hippocampal Activity Journal Article Forthcoming
In: Forthcoming.
@article{Lin2021c,
title = {Working Memory Performance after Daily Caffeine Intake: Compromised Performance and Reduced Hippocampal Activity},
author = {Y.-S. Lin and J Weibel and H.-P. Landolt and F Santini and H Slawik and S Borgwardt and C Cajochen and C. F. Reichert},
url = {http://www.chronobiology.ch/wp-content/uploads/2021/09/2021.04.19.440520v1.full_.pdf},
doi = {10.1101/2021.04.19.440520},
year = {2021},
date = {2021-04-20},
keywords = {},
pubstate = {forthcoming},
tppubtype = {article}
}
Lin, Y. -S.; Weibel, J.; Landolt, H.; Santini, F.; Meyer, M.; Brunmair, J.; Meyer-Menches, S.; gerner, C.; Borgwardt, S.; Cajochen, C.; Reichert, C. F.
In: Cerebral Cortex, 2021.
@article{Lin2021,
title = {Daily Caffeine Intake Induces Concentration-Dependent Medial Temporal Plasticity in Humans: A Multimodal Double-Blind Randomized Controlled Trial },
author = { Y.-S. Lin and J. Weibel and H. Landolt and F. Santini and M. Meyer and J. Brunmair and S. Meyer-Menches and C. gerner and S. Borgwardt and C. Cajochen and C. F. Reichert},
url = {http://www.chronobiology.ch/wp-content/uploads/2021/02/Lin_2021_CC_acc_uncorrect.pdf},
doi = {doi.org/10.1093/cercor/bhab005},
year = {2021},
date = {2021-02-15},
journal = {Cerebral Cortex},
abstract = {Caffeine is commonly used to combat high sleep pressure on a daily basis. However, interference with sleep–wake regulation could disturb neural homeostasis and insufficient sleep could lead to alterations in human gray matter. Hence, in this double-blind, randomized, cross-over study, we examined the impact of 10-day caffeine (3 × 150 mg/day) on human gray matter volumes (GMVs) and cerebral blood flow (CBF) by fMRI MP-RAGE and arterial spin-labeling sequences in 20 habitual caffeine consumers, compared with 10-day placebo (3 × 150 mg/day). Sleep pressure was quantified by electroencephalographic slow-wave activity (SWA) in the previous nighttime sleep. Nonparametric voxel-based analyses revealed a significant reduction in GMV in the medial temporal lobe (mTL) after 10 days of caffeine intake compared with 10 days of placebo, voxel-wisely adjusted for CBF considering the decreased perfusion after caffeine intake compared with placebo. Larger GMV reductions were associated with higher individual concentrations of caffeine and paraxanthine. Sleep SWA was, however, neither different between conditions nor associated with caffeine-induced GMV reductions. Therefore, the data do not suggest a link between sleep depth during daily caffeine intake and changes in brain morphology. In conclusion, daily caffeine intake might induce neural plasticity in the mTL depending on individual metabolic processes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Caffeine is commonly used to combat high sleep pressure on a daily basis. However, interference with sleep–wake regulation could disturb neural homeostasis and insufficient sleep could lead to alterations in human gray matter. Hence, in this double-blind, randomized, cross-over study, we examined the impact of 10-day caffeine (3 × 150 mg/day) on human gray matter volumes (GMVs) and cerebral blood flow (CBF) by fMRI MP-RAGE and arterial spin-labeling sequences in 20 habitual caffeine consumers, compared with 10-day placebo (3 × 150 mg/day). Sleep pressure was quantified by electroencephalographic slow-wave activity (SWA) in the previous nighttime sleep. Nonparametric voxel-based analyses revealed a significant reduction in GMV in the medial temporal lobe (mTL) after 10 days of caffeine intake compared with 10 days of placebo, voxel-wisely adjusted for CBF considering the decreased perfusion after caffeine intake compared with placebo. Larger GMV reductions were associated with higher individual concentrations of caffeine and paraxanthine. Sleep SWA was, however, neither different between conditions nor associated with caffeine-induced GMV reductions. Therefore, the data do not suggest a link between sleep depth during daily caffeine intake and changes in brain morphology. In conclusion, daily caffeine intake might induce neural plasticity in the mTL depending on individual metabolic processes.
2020
Reichert, C. F.; Veitz, S.; Bühler, M.; Gruber, G.; Deuring, G.; S. S. Rehm, K. Rentsch; Garbazza, C.; Meyer, M.; Slawik, H.; Lin, Y. -S.; Weibel, J.
Wide awake at bedtime? The effects of caffeine on sleep and circadian timing in teenagers - a randomized crossover trial. Journal Article
In: Biochemical Pharmacology, 2020.
@article{Reichert2020,
title = {Wide awake at bedtime? The effects of caffeine on sleep and circadian timing in teenagers - a randomized crossover trial.},
author = {C. F. Reichert and S. Veitz and M. Bühler and G. Gruber and G. Deuring and S. S. Rehm, K. Rentsch and C. Garbazza and M. Meyer and H. Slawik and Y.-S. Lin and J. Weibel},
url = {http://www.chronobiology.ch/wp-content/uploads/2021/09/1-s2.0-S0006295220305190-main.pdf},
doi = {https://doi.org/10.1016/j.bcp.2020.114283},
year = {2020},
date = {2020-10-15},
journal = {Biochemical Pharmacology},
abstract = {Adolescents often suffer from short and mistimed sleep. To counteract the resulting daytime sleepiness they frequently consume caffeine. However, caffeine intake may exaggerate sleep problems by disturbing sleep and circadian timing. In a 28-hour double-blind randomized crossover study, we investigated to what extent caffeine disturbs slow-wave sleep (SWS) and delays circadian timing in teenagers. Following a 6-day ambulatory phase of caffeine abstinence and fixed sleep-wake cycles, 18 male teenagers (14–17 years old) ingested 80 mg caffeine vs. placebo in the laboratory four hours prior to an electro-encephalographically (EEG) recorded nighttime sleep episode. Data were analyzed using both frequentist and Bayesian statistics. The analyses suggest that subjective sleepiness is reduced after caffeine compared to placebo. However, we did not observe a strong caffeine-induced reduction in subjective sleep quality or SWS, but rather a high inter-individual variability in caffeine-induced SWS changes. Exploratory analyses suggest that particularly those individuals with a higher level of SWS during placebo reduced SWS in response to caffeine. Regarding salivary melatonin onsets, caffeine-induced delays were not evident at group level, and only observed in participants exposed to a higher caffeine dose relative to individual bodyweight (i.e., a dose > 1.3 mg/kg). Together, the results suggest that 80 mg caffeine are sufficient to induce alertness at a subjective level. However, particularly teenagers with a strong need for deep sleep might pay for these subjective benefits by a loss of SWS during the night. Thus, caffeine-induced sleep-disruptions might change along with the maturation of sleep need.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Adolescents often suffer from short and mistimed sleep. To counteract the resulting daytime sleepiness they frequently consume caffeine. However, caffeine intake may exaggerate sleep problems by disturbing sleep and circadian timing. In a 28-hour double-blind randomized crossover study, we investigated to what extent caffeine disturbs slow-wave sleep (SWS) and delays circadian timing in teenagers. Following a 6-day ambulatory phase of caffeine abstinence and fixed sleep-wake cycles, 18 male teenagers (14–17 years old) ingested 80 mg caffeine vs. placebo in the laboratory four hours prior to an electro-encephalographically (EEG) recorded nighttime sleep episode. Data were analyzed using both frequentist and Bayesian statistics. The analyses suggest that subjective sleepiness is reduced after caffeine compared to placebo. However, we did not observe a strong caffeine-induced reduction in subjective sleep quality or SWS, but rather a high inter-individual variability in caffeine-induced SWS changes. Exploratory analyses suggest that particularly those individuals with a higher level of SWS during placebo reduced SWS in response to caffeine. Regarding salivary melatonin onsets, caffeine-induced delays were not evident at group level, and only observed in participants exposed to a higher caffeine dose relative to individual bodyweight (i.e., a dose > 1.3 mg/kg). Together, the results suggest that 80 mg caffeine are sufficient to induce alertness at a subjective level. However, particularly teenagers with a strong need for deep sleep might pay for these subjective benefits by a loss of SWS during the night. Thus, caffeine-induced sleep-disruptions might change along with the maturation of sleep need.
Weibel, J.; Lin, Y. -S.; Landolt, H. -P.; Garbazza, C.; Kolodyazhniy, V.; Kistler, J.; Rehm, S.; Rentsch, K.; Borgwardt, S.; Cajochen, C.; Reichert, C. F.
Caffeine-dependent changes of sleep-wake regulation: Evidence foradaptation after repeated intake Journal Article
In: Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2020.
@article{Weibel2020,
title = {Caffeine-dependent changes of sleep-wake regulation: Evidence foradaptation after repeated intake},
author = {J. Weibel and Y.-S. Lin and H.-P. Landolt and C. Garbazza and V. Kolodyazhniy and J. Kistler and S. Rehm and K. Rentsch and S. Borgwardt and C. Cajochen and C. F. Reichert },
url = {http://www.chronobiology.ch/1-s2-0-s0278584619304798-main-2/},
doi = {10.1016/j.pnpbp.2019.109851 },
year = {2020},
date = {2020-04-20},
journal = {Progress in Neuro-Psychopharmacology and Biological Psychiatry},
abstract = {Background: Circadian and sleep-homeostatic mechanisms regulate timing and quality of wakefulness. To enhance wakefulness, daily consumption of caffeine in the morning and afternoon is highly common. However, the effects of such a regular intake pattern on circadian sleep-wake regulation are unknown. Thus, we investigated if daily daytime caffeine intake and caffeine withdrawal affect circadian rhythms and wake-promotion in habitual consumers.
Methods: Twenty male young volunteers participated in a randomised, double-blind, within-subject study with three conditions: i) caffeine (150 mg 3 x daily for 10 days), ii) placebo (3 x daily for 10 days) and iii) withdrawal (150 mg caffeine 3 x daily for eight days, followed by a switch to placebo for two days). Starting on day nine of treatment, salivary melatonin and cortisol, evening nap sleep as well as sleepiness and vigilance performance throughout day and night were quantified during 43 h in an in-laboratory, light and posture-controlled protocol.
Results: Neither the time course of melatonin (i.e. onset, amplitude or area under the curve) nor the time course of cortisol was significantly affected by caffeine or withdrawal. During withdrawal, however, volunteers reported increased sleepiness, showed more attentional lapses as well as polysomnography-derived markers of elevated sleep propensity in the late evening compared to both the placebo and caffeine condition.
Conclusions: The typical pattern of caffeine intake with consumption in both the morning and afternoon hours may not necessarily result in a circadian phase shift in the evening nor lead to clear-cut benefits in alertness. The time-of-day independent effects of caffeine withdrawal on evening nap sleep, sleepiness and performance suggest an adaptation to the substance, presumably in the homeostatic aspect of sleep-wake regulation.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: Circadian and sleep-homeostatic mechanisms regulate timing and quality of wakefulness. To enhance wakefulness, daily consumption of caffeine in the morning and afternoon is highly common. However, the effects of such a regular intake pattern on circadian sleep-wake regulation are unknown. Thus, we investigated if daily daytime caffeine intake and caffeine withdrawal affect circadian rhythms and wake-promotion in habitual consumers.
Methods: Twenty male young volunteers participated in a randomised, double-blind, within-subject study with three conditions: i) caffeine (150 mg 3 x daily for 10 days), ii) placebo (3 x daily for 10 days) and iii) withdrawal (150 mg caffeine 3 x daily for eight days, followed by a switch to placebo for two days). Starting on day nine of treatment, salivary melatonin and cortisol, evening nap sleep as well as sleepiness and vigilance performance throughout day and night were quantified during 43 h in an in-laboratory, light and posture-controlled protocol.
Results: Neither the time course of melatonin (i.e. onset, amplitude or area under the curve) nor the time course of cortisol was significantly affected by caffeine or withdrawal. During withdrawal, however, volunteers reported increased sleepiness, showed more attentional lapses as well as polysomnography-derived markers of elevated sleep propensity in the late evening compared to both the placebo and caffeine condition.
Conclusions: The typical pattern of caffeine intake with consumption in both the morning and afternoon hours may not necessarily result in a circadian phase shift in the evening nor lead to clear-cut benefits in alertness. The time-of-day independent effects of caffeine withdrawal on evening nap sleep, sleepiness and performance suggest an adaptation to the substance, presumably in the homeostatic aspect of sleep-wake regulation.
Methods: Twenty male young volunteers participated in a randomised, double-blind, within-subject study with three conditions: i) caffeine (150 mg 3 x daily for 10 days), ii) placebo (3 x daily for 10 days) and iii) withdrawal (150 mg caffeine 3 x daily for eight days, followed by a switch to placebo for two days). Starting on day nine of treatment, salivary melatonin and cortisol, evening nap sleep as well as sleepiness and vigilance performance throughout day and night were quantified during 43 h in an in-laboratory, light and posture-controlled protocol.
Results: Neither the time course of melatonin (i.e. onset, amplitude or area under the curve) nor the time course of cortisol was significantly affected by caffeine or withdrawal. During withdrawal, however, volunteers reported increased sleepiness, showed more attentional lapses as well as polysomnography-derived markers of elevated sleep propensity in the late evening compared to both the placebo and caffeine condition.
Conclusions: The typical pattern of caffeine intake with consumption in both the morning and afternoon hours may not necessarily result in a circadian phase shift in the evening nor lead to clear-cut benefits in alertness. The time-of-day independent effects of caffeine withdrawal on evening nap sleep, sleepiness and performance suggest an adaptation to the substance, presumably in the homeostatic aspect of sleep-wake regulation.
2019
Lin, Y. -S.; Fusar-Poli, P.; Borgwardt, S.
Neuroimaging and the At-Risk Mental State Book Chapter
In: Galderisi, Silvana; DeLisi, Lynn E; Borgwardt, Stefan (Ed.): Neuroimaging of Schizophrenia and Other Primary Psychotic Disorders : Achievements and Perspectives, pp. 219–265, Springer International Publishing, Cham, 2019, ISBN: 978-3-319-97307-4.
@inbook{Lin2019,
title = {Neuroimaging and the At-Risk Mental State},
author = {Y.-S. Lin and P. Fusar-Poli and S. Borgwardt},
editor = {Silvana Galderisi and Lynn E DeLisi and Stefan Borgwardt},
url = {https://doi.org/10.1007/978-3-319-97307-4_6},
doi = {10.1007/978-3-319-97307-4_6},
isbn = {978-3-319-97307-4},
year = {2019},
date = {2019-01-01},
booktitle = {Neuroimaging of Schizophrenia and Other Primary Psychotic Disorders : Achievements and Perspectives},
pages = {219--265},
publisher = {Springer International Publishing},
address = {Cham},
abstract = {The prodromal state of schizophrenia has excited the attention of researchers since the 1990s. The long-term course of schizophrenia increases the individual burden to caregivers and causes considerable financial costs to society. With early detection and intervention in schizophrenia, it might be possible to decrease the risk of irreversible deterioration after continual relapses.},
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pubstate = {published},
tppubtype = {inbook}
}
The prodromal state of schizophrenia has excited the attention of researchers since the 1990s. The long-term course of schizophrenia increases the individual burden to caregivers and causes considerable financial costs to society. With early detection and intervention in schizophrenia, it might be possible to decrease the risk of irreversible deterioration after continual relapses.