The Paradoxical Effect of Sleep Deprivation on Mood: Increased Amygdala–ACC Connectivity May Be the Key

Sleep deprivation is a common phenomenon in modern society, affecting millions of people worldwide. Lack of sleep can impair cognitive functions, memory, attention, and emotional regulation.

However, paradoxically, sleep deprivation can also have a beneficial effect on mood for some individuals, especially those suffering from depression.

This paradoxical effect has been attributed to changes in the connectivity between the amygdala and the anterior cingulate cortex (ACC).

What is the amygdala-cingulate circuit?

The amygdala is a small almond-shaped structure located deep in the temporal lobe of the brain. It is involved in processing emotional stimuli, especially those related to fear, threat, and stress. The amygdala also modulates other brain regions involved in emotion regulation, such as the prefrontal cortex and the anterior cingulate cortex (ACC).

The ACC is a part of the medial frontal lobe that plays a key role in cognitive control, conflict monitoring, error detection, and emotional regulation. The ACC also interacts with other brain regions involved in mood regulation, such as the dorsal nexus (DN), which is a network of brain regions that show abnormal activity in depression.

The amygdala-cingulate circuit is a functional connection between the amygdala and the ACC that reflects their coordinated activity during emotional processing. This circuit has been implicated in various aspects of mood regulation, such as resilience, coping, and recovery from negative emotions.

How does sleep deprivation affect the amygdala-cingulate circuit?

Sleep deprivation is known to increase amygdala activity and reactivity to negative emotional stimuli, such as angry faces or unpleasant images. This suggests that sleep deprivation impairs the ability to regulate negative emotions and increases emotional vulnerability.

However, sleep deprivation can also enhance amygdala connectivity to the ACC, which may reflect an adaptive mechanism to cope with increased emotional demands. This enhanced connectivity may facilitate emotional regulation by increasing cognitive control and conflict resolution.

A recent study by Chai et al. (2023) investigated how sleep deprivation affects amygdala-cingulate connectivity and mood in both healthy adults and patients with major depressive disorder (MDD). The study used functional magnetic resonance imaging (fMRI) to measure resting-state brain activity before and after one night of total sleep deprivation (TSD) in a controlled laboratory setting.

The study found that TSD increased negative mood in healthy participants but reduced depressive symptoms in 43% of patients with MDD. The study also found that TSD enhanced both amygdala- and DN-related connectivity in healthy participants. Moreover, enhanced amygdala connectivity to the ACC after TSD associated with better mood in healthy participants and antidepressant effects in depressed patients.

These findings suggest that the amygdala-cingulate circuit plays a key role in mood regulation in both healthy and depressed populations and that enhancing this circuit may have therapeutic potential for depression.

What are the implications and limitations of using sleep deprivation as a treatment for depression?

Sleep deprivation has been used as an experimental intervention for depression since the 1970s. It has been shown to induce rapid and transient antidepressant effects in about 50% of patients with MDD, especially those with melancholic or bipolar features. However, the mechanisms underlying this effect are still unclear and the clinical applicability of sleep deprivation is limited by several factors.

First, sleep deprivation is not a sustainable or safe treatment option, as it can cause serious adverse effects on physical and mental health, such as impaired immunity, metabolism, cognition, memory, attention, and mood stability. Moreover, sleep deprivation can trigger manic episodes in patients with bipolar disorder or increase suicidal risk in patients with severe depression.

Second, sleep deprivation is not a specific or selective treatment for depression, as it can affect various brain regions and neurotransmitter systems that are not necessarily related to depression. For example, sleep deprivation can increase dopamine levels in the striatum, which may contribute to its antidepressant effect but also cause psychotic symptoms or addiction-like behaviors.

Third, sleep deprivation is not a durable or reliable treatment for depression, as its antidepressant effect is usually short-lived and reversed by subsequent recovery sleep. Therefore, sleep deprivation needs to be combined with other treatments, such as pharmacotherapy or chronotherapy (i.e., manipulating circadian rhythms), to maintain or enhance its effect.

The new study ….

A recent study published in the Proceedings of the National Academy of Sciences (PNAS) provides further evidence for the role of amygdala–ACC connectivity in mood regulation. In this study, researchers conducted functional magnetic resonance imaging (fMRI) scans on healthy adults and patients with major depressive disorder (MDD) before and after one night of total sleep deprivation (TSD).

The results showed that TSD increased connectivity between the amygdala and the ACC in both healthy adults and patients with MDD. This increase in connectivity was associated with better mood in both groups. In the patients with MDD, the increase in connectivity was particularly pronounced in those who showed a significant improvement in mood after TSD.

These findings suggest that amygdala–ACC connectivity may be a key target for the development of new antidepressant treatments. By targeting this circuit, it may be possible to induce a rapid and lasting improvement in mood in people with depression.

Implications for future research

The findings of this study have several implications for future research. First, they suggest that TSD may be a useful tool for investigating the neural mechanisms of mood regulation. Second, they suggest that amygdala–ACC connectivity may be a biomarker for predicting who is likely to benefit from TSD as an antidepressant treatment. Third, they suggest that targeting amygdala–ACC connectivity may be a promising approach for developing new antidepressant treatments.

Limitations of the study

There are a few limitations to this study that should be considered. First, the study was conducted in a relatively small sample of participants. Second, the study only examined the effects of TSD on mood in the short-term. It is possible that the effects of TSD on mood may be different in the long-term.

Future directions

Future studies should aim to replicate the findings of this study in a larger sample of participants. These studies should also examine the effects of TSD on mood in the long-term. Additionally, future studies should investigate the effects of TSD on other aspects of mood regulation, such as anxiety and stress.

Conclusion

The findings of this study suggest that amygdala–ACC connectivity is a key target for the development of new antidepressant treatments. By targeting this circuit, it may be possible to induce a rapid and lasting improvement in mood in people with depression.

References

• Enhanced amygdala–cingulate connectivity associates with better mood in both healthy and depressive individuals after sleep deprivation: https://www.pnas.org/doi/10.1073/pnas.2214505120