Neurocognitive basis of the association between chronotype and fear responses in humans


Chronotypes are our circadian preference profiles, that is, they refer to the differences in performance that each person has in relation to the periods of sleep and wakefulness throughout the 24 hours of the day.

We can be morning type (if we prefer to wake up early and have a good performance in activities that start in the morning), evening type (if we are more productive at night or at dawn and prefer to stay up later), or intermediate (if we easily adapt to morning and evening schedules).

Circadian rhythms have been increasingly studied because they can help to understand the onset of mental disorders such as anxiety and post-traumatic stress disorder (PTSD). In this sense, researchers Chiara Lucifora, Giorgio M. Grasso, Michael A. Nitsche, Giovanni D’Italia, Mauro Sortino, Mohammad A. Salehinejad, Alessandra Falzone, Alessio Avenanti and Carmelo M. Vicario resorted to the classic Pavlovian paradigm of fear conditioning to study the neurocognitive basis of the association between chronotype and fear responses in healthy humans.

In the paper “Enhanced fear acquisition in individuals with evening chronotype. A virtual reality fear conditioning/extinction study”, published in the Journal of Affective Disorders, in August 2022, the researchers from Università Degli Studi di Messina and Università di Bologna (Italy), Leibniz Research Center for Working Environment and Human Factors (Germany) and Universidad Católica Del Maule (Chile) explain that they used 40 participants recruited among students from the University of Messina, 20 with evening chronotype and 20 controls (i.e., intermediate chronotype) to complete a 2-day Pavlovian fear learning and extinction virtual reality task.

“To the best of our knowledge, only one study (Pace-Schott et al., 2015) to date explored the role of chronotypes on fear acquisition and extinction in healthy humans, but did not test intermediate chronotypes, the ideal control group as they are the most frequent chronotype in the population (Partonen, 2015)”, explains Carmelo M. Vicario, a researcher supported by the BIAL Foundation.

The results obtained in the two groups showed a higher fear acquisition response in evening chronotype individuals, compared to intermediate chronotype participants, confirming prior evidence that associated the evening chronotype with a higher risk of anxiety disorders (Alvaro et al., 2014; Park et al., 2015) and PTSD (e.g., Hasler et al., 2013; Yun et al., 2015).

“This study provides new insights about the influence of circadian rhythms on cognitive and affective processes, suggesting that the higher vulnerability of the evening chronotype to anxiety and related disorders may be mediated by altered fear acquisition,” says Vicario.

The present study shows that late (evening) types score higher on a specific psychological factor of depression vulnerability, namely cognitive reactivity. Cognitive reactivity and its rumination subscale were related to eveningness and were significant mediators of the relationship between chronotype and depression, even after correcting for related factors such as insomnia and neuroticism (known to be associated with depression (Kendler et al., 2006; Van Mill et al., 2010)). This statistical mediation remained significant when examining recovered depressed individuals versus controls (as outcome), indicating that eveningness is not a result of current depressive symptomatology, but most likely a risk factor for increased depressive cognitions, and consequently depression. Worry was not related to chronotype and was not a significant mediator of the link between chronotype and depression. Worry levels were within the average range according to norms (Van Der Heiden et al., 2009). Cognitive reactivity levels, especially for the late type, were similar to those reported by recovered depressed patients (Antypa et al., 2010).

This is the first study that has examined a depression-specific cognitive vulnerability factor in relation to chronotypes. Cognitive reactivity has been established as a vulnerability factor of depression in prior studies. In a prospective analysis of the NESDA sample, we found that higher cognitive reactivity predicted the onset of depression in a healthy group (Kruijt et al., 2013). Furthermore, higher cognitive reactivity measured with the LEIDS-R was also found to be a predictor of relapse in a longitudinal study, with the rumination subscale being the best predictor (Figueroa et al., 2015). We have shown previously that rumination reactivity is a unique cognitive construct related to MDD (and not to dysthymia or anxiety disorders) (Drost et al., 2012). Rumination measured with other scales (Nolen-Hoeksema, 2000) is a known predictor of depression, as well as a maintaining factor (Nolen-Hoeksema et al., 2008). With regard to the other subscales of cognitive reactivity, we observed that risk aversion was higher in evening types. Prior research has associated evening types with higher harm avoidance traits (Hsu et al., 2012), although conflicting findings have been reported on this trait (Adan et al., 2010). Overall, our findings showing higher cognitive vulnerability in late types are in line with recent research showing that depressed individuals who are evening types report more cognitive symptoms (both upon admission and dismissal), whereas no differences are found on somatic and affective symptoms between morning- and evening- type patients (Muller et al., 2016b).

With regard to the lack of an association between worry and chronotypes, results are not entirely surprising considering that worry and rumination share some similar qualities (such as negative repetitive thinking) but they are different also on a number of issues. These issues are time orientation (worry is future-oriented, rumination is present–past oriented) and thought content (worry is more related to threat anticipation whereas rumination reflects more deeper meaning and emotion analysis) (see Nolen-Hoeksema et al. (2008) for a thorough distinction). We also previously observed that worry was uniquely associated with generalized anxiety disorder and not with MDD when cognitive reactivity is taken into account (Drost et al., 2012). This adds to the current understanding of the role of chronotype in depressive and anxiety disorders. In particular, it seems that the association with the late type is specific to MDD (and not anxiety) (Antypa et al., 2016) and to rumination (and not worry) as potential underlying mechanisms.

Insomnia, although predictive of depression in our models, was not related to eveningness (Table 1); in fact, eveningness has been associated previously with hypersomnia (Vernet & Arnulf, 2009). Neuroticism has been previously associated with eveningness (Randler, 2008; Tonetti et al., 2009), but not consistently so. Other studies, consistent with the present study, do not show differences on this trait between early and late chronotypes (Gray & Watson, 2002; Hogben et al., 2007; Jackson & Gerard, 1996). Other research on personality styles has shown that optimism and happiness are higher among morning types, whereas pessimism is associated with eveningness (Antúnez et al., 2015; Levy, 1985); this is in line with our observation of increased depressive cognitions (cognitive reactivity) also in healthy late types. With regard to this aspect, we observed from our post hoc analyses that late healthy types are more likely to have higher cognitive reactivity levels on a range of subscales including rumination and the total score, whereas fewer associations were found in the remitted group and even less in the currently depressed group. This is not contrary to expectation, since the questionnaire (the LEIDS-R) is addressed to participants who are not in the middle of a depressive episode, since they have to imagine themselves to be “somewhat sad” and how they would react cognitively to this mild sad mood. We have previously shown that the scale is able to capture vulnerability to depression in healthy participants and to predict prospectively the onset of depression (Kruijt et al., 2013).

The present study has several strengths. Our large sample is comprised of participants with current and/or past clinically diagnosed depression as well as a healthy group, and participants are recruited from different areas (community, general practitioners and mental health organizations). MDD diagnosis was based on clinical interviews and the various additional assessments in the study allowed us to control for and take into account a number of factors (sociodemographic and clinical factors) in our analyses.

A limitation of the present report is its cross-sectional nature, precluding any inferences on causality from the mediation models. Future studies should apply a prospective design in order to assess the issue of timeline. Also, although the mediation models do not provide effect size estimates, we can observe that coefficients were not very large and differences in cognitive reactivity between chronotype categories (Table 2) range from moderate to low effect sizes. Since this is the first study examining cognitive reactivity and rumination in relation to chronotype and depression, the size of such effects remains to be further determined. Finally, it should be noted that we used the MCTQ as a measure of chronotype assessment, whereas most prior studies examining the association between chronotype and depression (Chan et al., 2014; Chelminski et al., 1999; Kitamura et al., 2010; Merikanto et al., 2013; Muller et al., 2016a) have used the Morningness–Eveningness Questionnaire (Horne & Ostberg, 1976). The MCTQ correlates with the MEQ (r = – 0.73) (Zavada et al., 2005) and while the MCTQ reflects actual sleep patterns during work days and free days, the MEQ represents a more global preference for sleep patterns as well as for performing mental and physical activities either in early or late hours (Adan et al., 2012).

Clinical considerations
Eveningness has been found to be a predictor of non-remission (odds ratio = 3.36), independent of insomnia severity, in patients with MDD, with such patients reporting higher depressive symptomatology and suicidality (Chan et al., 2014). Similarly, eveningness has been found to be associated with impairments in remitted bipolar disorder, where evening types were more associated with a worse outcome in several functional aspects (such as sleep–wake problems, dietary habits and interpersonal relationships) and they also reported higher sleep-related dysfunctional cognitions (Ng et al., 2016). Such studies indicate the clinical relevance of targeting eveningness during treatment.

Evening types have a particular sleep rhythm (i.e. late bed time, late awake time and social jetlag) and it could be assumed that shifting the clock time could have beneficial results in mood-related aspects in this group. Jankowski (2015) recently examined this hypothesis in a longitudinal design and found that the natural shift toward an earlier chronotype in terms of earlier bedtime, longer sleep duration, and decrease in sleep-onset latency and social jetlag was not accompanied by an improvement in mood or life satisfaction. On the other hand, another study showed that a shift to morningness was associated with lower depression and increased positive affect and sleep quality, after a behavioral treatment for insomnia or an information intervention (changes applied to both groups, n = 29) (Hasler et al., 2016). The latter study, either through active treatment or psychoeducation, managed to improve both sleep- and mood-related aspects together with a shift to morningness. Assuming that evening types are more vulnerable to depressogenic cognitions (as shown in our study), a combination of cognitive/behavioral treatments and chronotherapeutics may be preferred as compared to phase-shift treatments alone. Eveningness is a promising target during treatment (Chan et al., 2014; Ng et al., 2016), but also a potential “alarm” in young vulnerable populations, that should be taken into account during early monitoring and prevention.

reference link:

Original Research: Closed access.
Enhanced fear acquisition in individuals with evening chronotype. A virtual reality fear conditioning/extinction study” by Chiara Lucifora et al. Journal of Affective Disorders


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