COVID19 & PSYCHIATRY: THE MISSING LINK

Abraham Peled M.D.

A review by Ravi Philip Rajkumar (2020) summarizes the literature and finds that preliminary evidence suggests 16-28% reports about anxiety and depression are related to the COVID-19 pandemic. Another review emphasizes the risk of increase in vulnerability to Post-Traumatic Stress, Depressive, and Anxiety Disorders, as well as grief-related symptoms in adolescents (Selim et al 2020). Additional survey (Vindegaard et al 2020) also emphasized the significantly higher level of depressive symptoms. But also mentioned the patients with pre-existing psychiatric disorders and reported that they have worsening of psychiatric symptoms. This review also investigating health care workers and found that also in these populations there was increased depression, anxiety and psychological distress. Ahmed et al 2020 emphasize the neurological risks of Encephalitis, Meningitis, acute cerebrovascular disease, and Guillain Barré Syndrome in severely diseased COVID-19 patients. One non reviewed paper found histopathological signs of brain damage in 25% of individuals who died of COVID-19. This non-reviewed paper also repeated the finding putting COVID-19 related depression and anxiety at approximately 20%. It is possible to summarize that mood and anxiety disorders are typical psychiatric findings that have been related to the pandemic. Direct brain pathology such a Encephalitis and other forms of damage to the neurons are a possibility but are not a prominent finding, it seems more secondary to serious infections that have span out of control.

So how dose COVID-19 causes Depression if not by direct damage to neurons?

In order to answer this question, we first need to translate Depression into its underlying brain disturbance and then see how COVID-19 pandemic triggers such disturbance. To do that we shall use the recently conceived theory-based advancements in computational neuroscience (Peled 2013; Peled and Geva 2013).

It is well known that antidepressant medication effect takes approximately 6 weeks, and that it is correlated with synaptogenetic mechanism (Peled 2013). Thus, plasticity of brain networks has a crucial effect in the antidepressant outcome.

But how dose increase in brain plasticity elevates mood?

This has to do with brain optimization dynamics. We know that the brain is a Bayesian brain (Friston 2012), continually adapting to the environment optimizing internal configurations (expectations) according to environmental occurrences. Expectations met, are coupled with satisfaction and elevated mood. Expectations unmet (frustration) are accompanied by depressed mood. Brain Networks responsible for Bayesian matching are the Salient Networks regulating the interactions between the Executive Central Networks and the Default Mode Networks. If these networks are plastic due to synaptogenesis they can change and adapt rapidly offering effective increased Bayesian dynamics and adaptability. Thus, increased plasticity offers more optimization of expectations thus a capacity for elevated mood and resistance to frustrating depressed reactions.

The occurrences related to COVID-19 are those of loss, and social change (isolation) which go against the normal expected occurrences of regular pre-COVID occurrences. The Bayesian brain is deoptimized as expectations are not met by the new COVID-conditions. Unmet expectations and frustration trigger depressed mood. Adaptation to the new situation requires plasticity for restoration of mood balance. Thus the equilibrium between plasticity–induced brain-adaptability and environmental deoptimized COVID-occurrences, will determine the emergence of depressive episodes.

To summarize COVID-19 triggers depression indirectly by influencing life-occurrences which deoptimize Bayesian brain dynamics and result in depressed mood due to mismatch and non-adaptive plasticity mechanisms. In this model both the environmental changes and the biological neuronal factors play part. If some biological injury to the neurons hampers neuronal plasticity then the brain loses adaptability and deoptimizes it capacity to familiarize to the everchanging environment. If the environment changes markedly due to pandemic consequences then the burden of adaptability increases and frustrating mismatch ensues. Both conditions result in depressed mood, and if happen together then depression certainly follows.

Based on the above, it seems that COVID-19 pandemic offers a unique opportunity to study depression by analyzing big-data of brain imaging obtained by wearable devices applied to large infected populations thus collecting big-data of phenomenology synchronized with measurements of brain dynamics over time (optimization).                                     

References

Ravi Philip Rajkumar  COVID-19 and mental health: A review of the existing literature Asian J Psychiatr . 2020 Aug;52:102066.

Sélim Benjamin Guessoum , Jonathan Lachal , Rahmeth Radjack , Emilie Carretier , Sevan Minassian , Laelia Benoit , Marie Rose Moro. Adolescent psychiatric disorders during the COVID-19 pandemic and lockdown Psychiatry Res 2020 Sep;291:113264.

Nina Vindegaard , Michael Eriksen Benros.  COVID-19 pandemic and mental health consequences: Systematic review of the current evidence Brain Behav Immun 2020 Oct;89:531-542.

Muhammad Umer Ahmed, Muhammad Hanif , Mukarram Jamat Ali , Muhammad Adnan Haider , Danish Kherani , Gul Muhammad Memon , Amin H Karim 5, Abdul Sattar.  Neurological Manifestations of COVID-19 (SARS-CoV-2): A Review  

Peled A Brain "Globalopathies" cause mental disorders. Med Hypotheses. 2013 Dec;81(6):1046-55.

Peled A, Geva AB. "Clinical brain profiling": a neuroscientific diagnostic approach for mental disorders. Medical Hypothesis 2013

Karl Friston The history of the future of the Bayesian brain Neuroimage. 2012 Aug 15;62(2):1230-3.