Societal shifts have sparked interest in understanding the impact of a person’s chronotype on brain and behavior, a manifestation of circadian rhythms that can be effectively assessed through self-reporting44. In our population neuroscience study, we draw on the chronotype phenotype, as defined by the UK Biobank initiative, a rich portfolio of lifestyle indicators and three brain image modalities (region volume, functional connectivity and white-matter fiber tracts) in 27,030 UK biobank participants to investigate the neurobiology of early risers vs. night owls.
Our PheWAS on chronotype showed that morningness was significantly associated with higher blood levels of vitamin D, probably reflecting early riser’s exposure to more light, as light exposure is a key factor in what orchestrates circadian timing of the sleep-wake cycle11,45. This finding confirmed the neurophysiological distinctions between night owls and early risers, and also validated our grouping approach. Importantly, since chronotype has a close relationship with sleep duration and inadequate sleep has been shown to impact emotional and cognitive functions46–49, we regressed out the effects of sleep duration, napping during the day, sleeplessness, snoring, and daytime dozing sleeping, before conducting brain classification analyses to predict whether an individual is an early riser or night owl. Thus, the observed effects of chronotype were not attributed to the differences in sleep.
As previously reported, individuals with an evening chronotype often face higher health risks3,22,50,51. This tendency is strongly linked to their misalignment with societal schedules, forcing individuals adjust their sleep patterns to meet social expectations. As a result, eveningness people experience increased tiredness during the daytime, which leads to the phenomenon known as social jetlag17. In line with previous study17,52, our chronotype PheWAS results confirmed that evening types tend to be more tiredness, and consume higher amounts of tobacco and alcohol, presumably. In addition, our PheWAS indicated that individuals who have a preference for being active at night are more prone to attend club activities, thus increase their risk of encountering social jetlag. In sum, the unhealthy lifestyle choices of night owls may be key factors mediating their higher susceptibility of the health issues compared to the early risers.
On a larger canvas, a recent 37-year prospective longitudinal study about chronotype and mortality highlights that chronotype, in itself, may not be the primary contributor to mortality; instead, it was argued that lifestyle choices play a crucial role53. Nonetheless, there is a notable association between chronotype and lifestyle regularity, with morning individuals often adhering to more consistent daily routines while evening chronotypes tend to lean toward unhealthy and less regular life rhythms3,54. For instance, people of the eveningness chronotype exhibit a preference for eating late at night, frequently skipping breakfast, consuming un-fresh or highly processed foods6, and engaging in lower levels of physical activity55. Night owls’ lifestyle habits may contribute to the higher prevalence of obesity and related health issues often observed among evening chronotypes4,5,28. In alignment with these earlier findings and reflections, our present PheWAS findings reinforce previous reports that night owls tend to be more likely to have a higher BMI and engage in less physical activity. These sustained unhealthy behaviors are recognized for eliciting significant and distinct neurobiological changes, including reduced brain volume56,57, and deficits in grey matter within areas like the prefrontal cortex and hippocampus58. These neural substrates, involved in emotion regulation and reward processing, are believed to play a critical role in influencing the formation of healthy habits as well as mental health.
The evident disparities in lifestyles between morningness and eveningness suggest potential manifestations in the brain networks associated with habit formation. The process of acquiring a new habit involves a shift in behavioral control from goal-directed cognitive effort to stimulus-response behavior, which was previously reported to be regulated by brain networks, transitioning from the associative prefrontal/cortical-basal ganglia network to the sensorimotor cortico-basal ganglia network as the new habit becomes established59,60. Our present examination of regional GMV revealed that the influence of chronotype is evident in both goal-directed brain regions (such as the hippocampus and orbitofrontal cortex) and stimulus-response brain regions (including the putamen, precentral gyrus, and cerebellum) among the neural systems thought to be involved in habit formation. Furthermore, consistent with these findings in brain morphology, we found that chronotype differences also related to varying functional connections within the basal ganglia, posteromedial cortex, primary somatosensory cortex, and cerebellum.
Stress has previously been found to be a crucial factor in facilitating habit formation61, with the release of cortisol (a stress hormone from the adrenal gland) a critical element in the transition between "cognitive" and "habit" learning systems61,62. In addition, in neurophysiology, the major circuit related to cortisol control, the hypothalamic–pituitary–adrenal (HPA) axis, is also known to modulate hippocampus, orbitofrontal prefrontal cortex (OFC), and basal ganglia62,63, which were all apparent in our brain correlates of chronotype. Akin to chronotype’s impact on daily life rhythm, cortisol also shows a circadian rhythm8. Indeed, a study in real-life settings confirmed that forming a new health behavior is easier in the morning than in the evening which modulated through diurnal variation in blood cortisol levels64. Moreover, the morning types exhibited higher cortisol levels, on average, than evening types right after waking up65. Cortisol secretion, in biological substances, is closely regulated by the hypothalamic suprachiasmatic nucleus (SCN)66,67, which serves as the primary circadian pacemaker in the body. Interestingly, variations in the expression of clock genes in the SCN would exert wide-ranging effects on the chronotype-related behavioral tendencies, which supports the view that chronotype at least in part is due to clock speed, with a (genetically) faster running clock resulting in an advanced phase angle under solar day entrained conditions, i.e. an earlier chronotype2,8. Taken together with present and previous findings, the close relationship between chronotype and cortisol secretion may be another factor that impacts the formation of new habits.
The OFC founded in our results are known to be closely interconnected with the brain reward system, exerting a crucial role in regulating how individuals respond to stimuli and influence their behaviors. In light of previous findings, OFC can be assumed to hold a key role in signaling both the value and specific identity of rewards68–70, with the latter being learned and updated through the correction of identity errors in the dopaminergic midbrain71, contributing to outcome-guided behaviors. Dysfunctions in the OFC are known to precipitate symptoms of anhedonia, a condition characterized by a reduced ability to experience pleasure, and are closely associated with substance use disorder72,73, obsessive-compulsive disorder74–76, and depression77,78. Aligning with these neurobiological insights, our chronotype PheWAS results have indicated a higher susceptibility to addiction in night owls, who exhibit a greater tendency to consume alcohol, tobacco and cannabis, all behaviors known to trigger the release of dopamine in the brain's reward centers79,80. These behaviors, closely tied to the functioning of the OFC and other reward-related brain regions, brings into focus the intriguing link between chronotype and vulnerability to addiction, to be detailed in future neuroscience research.
Growing evidence shows that emotional struggles are prevalent among evening people18,22,50. Our chronotype PheWAS results corroborate these earlier observations, highlighting that late chronotypes are more likely to experience negative emotions, such as feelings of tiredness, unenthusiasm, feed-up sentiments, mood swings, and increased neuroticism. Further, consistent with prior research7,9,10, the late chronotypes also exhibit a greater propensity for depression when compared to early risers. A previous study reasoned that ineffectiveness in emotion regulation may partially contribute to the heightened vulnerability of late chronotypes to depressive symptoms81. In line with behavior observations, our neurobiological findings identify the regional grey matter volume of OFC, subcallosal cortex (SCC), paracingulate gyrus, hippocampus and parahippocampal areas that played vital roles in classifying different chronotypes. These brain regions are key components of the limbic system, a hub for emotional processing and regulation82–85.
Specifically, the OFC was shown to be related to the reappraisal of negative stimuli86, which also project extensively to the amygdala, and are crucial in regulating fear learning and the extinction of fear responses87,88. These mechanisms may contribute to the tendency of night owls for impulsivity89,90, as evidenced by our chronotype PheWAS results showing a greater likelihood of exceeding motorway speed limits among this group. Furthermore, a PET study showed people with higher attachment avoidance have fewer endorphin receptors in the OFC, suggested people with more endorphin receptors may need more social contact to satisfy their need91. The close interaction between the OFC and endorphin receptors may be a part of the reason that the night owls encounter more conflicts in their social lives, as our PheWAS showed, they feel more loneliness than early risers. On the other hand, the SCC conveys automatic, negative affective valuations, and is implicated in negative mood states, such as anhedonia and depression92–94. A monkey lesion study also revealed that SCC is a critical region for maintaining heightened autonomic arousal when anticipating rewards and plays a role in regulating emotions85. Moreover, both OFC and SCC were known to be densely interconnected with the hypothalamus in primates95,96, shedding light on candidate mechanisms that may link chronotype to emotional experiences, with relevance to chronotype-related behaviors.
In addition to the OFC and SCC, our study also emphasizes the hippocampus, a well-established contributor to the pathophysiology of depression97,98. Consistent with the structural MRI findings, the microstructural integrity of the fornix, a core fiber tract originating from the hippocampus and extending to the OFC/medial prefrontal cortex and subcortical areas such as the hypothalamus and striatum99,100, was highlighted in our diffusion MRI results. The involvement of the hippocampus and the highlighted microstructural properties of the fornix offers a comprehensive perspective on how the chronotype-related emotional patterns manifest at neural levels, illuminates potential pathways through which late chronotypes may be more susceptible to depressive symptoms.
Apart from implication in habit formation and sleep-wake cycles60,101, the basal ganglia in our results also have implications for mood disorders, including bipolar disorder102–104. Activation of the putamen in response to noxious stimuli underscores its importance in processing negative sensory information, potentially influencing emotional states and regulation105. Our resting-state fMRI findings further substantiate the differences in functional connectivity between the basal ganglia and the primary somatosensory cortex among individuals with varying chronotypes. Moreover, the basal ganglia, intertwined within the prefrontal-limbic network, influences both goal-directed and habit-learning behaviors, offering insights into major depressive disorders who have symptoms of sad mood and loss of interest in activities once enjoyed106. Additionally, the prefrontal-limbic network also interconnects with the hypothalamus, which serves as a central regulator controlling hormone secretion and acting as the bridge between the limbic system and the HPA axis106,107. Above all, their complex interactions collectively contribute to the intricate regulation of emotional processing and stress responses, closely interlocked with an individual's chronotype and susceptibility to affective disorders.
As a central finding from our present investigation, our population neuroscience study may be the first in highlighting the involvement of the cerebellum in chronotype; an insight that consistently emerged from all three examined brain-imaging modalities. Despite being routinely overlooked in prior research dedicated to chronotypes, the cerebellum has been known to play a pivotal role in habit formation and habit expression108–110, and associated with unexpected rewards and emotional experiences 111,112. Moreover, the cerebellum was already known to be implicated in regulating the sleep–wake cycle113–115, while tissue damage in this region can cause sleep disorders116,117. Furthermore, the cerebellum has close structural and functional connections to the basal ganglia, hippocampus, OFC, and anterior cingulate cortex, which are all prominently featured in our findings, further underscoring its potential importance for chronotype118,119. Several of these partner regions are vital components of the limbic brain circuitry, regulating affective processes like emotion regulation and motivation118,119. In line with these present and previous observations, our diffusion MRI results additionally identified the cerebral peduncle and superior cerebellar peduncle, which are axonal fiber bundles connecting the cerebellum to the brain stem and the cerebrum120,121. Furthermore, the resting state fMRI results also revealed the significance of the functional connectivity between the basal ganglia and cerebellum. In summary, our findings advocate that the cerebellum, especially vermis, should be treated as a first-class citizen in future neuroscience research on chronotypes.
Integrating our findings with the roles of these brain regions in habit formation, the reward system, emotional regulation, and the neural circuits linked to chronotype, our study provides insights into the fundamental neurobiological associations among the chronotype, habit formation, addictive behaviors, as well as mental health challenges. This emerging understanding can serve as a basis for customized treatment interventions and strategies aimed at aligning habits with their inherent biological predispositions122.
Prior research has shown that women tend to exhibit a more pronounced morningness in their youth. Yet, these male-female differences tend to diminish or even reverse in mid to later stages of life12–16. Our present study involved participants in mid to late adulthood, with an average age of 55.4 ± 7.4 years, ranging from 40 to 70 years at the time of enrollment. Consistent with earlier observations, we found that the chronotype prevalence itself did not exhibit significant differences between males and females in our study (t = -0.99, p = 0.31 as two-sample t-test). However, in terms of the neural correlates of chronotype, differences between male and female groups are still evident. In line with our main findings on the GMV of the OFC, the sex-specific results revealed a stronger positive association with eveningness in females compared to males. Notably, women have been shown to have a greater GMV in the OFC than men123, further confirming the tight connections between OFC and chronotype. Previous research has also suggested that sex differences on OFC were closely associated with the differentials on emotional regulation and stress response circuitry between female and male124,125. Moreover, in alignment with a recent study focusing on sex-based differences in the social brain126, our multimodal findings also indicated the sex differences in relation to the limbic system in respect of chronotype. This included variations in the GMV of the OFC, thalamus, temporal lobe, and structural integrity of the uncinate fasciculus, sagittal stratum, as well as the function couplings related to cingulate cortex, basal ganglia, posteromedial cortex. Collectively, there might exist sex-specific patterns in the relationship between chronotype and associated aspects, warranting further exploration.