Special issue editorial: Personalized medicine in psychiatry in the COVID-19 era: Fighting the impact of the pandemic on mental health

1. Introduction

The coronavirus disease 2019 (COVID-19) pandemic is the defining global health crisis of the 21st century and it represents the greatest health challenge since the two World Wars [1], [2] and perhaps the HIV epidemic.

The 2019 coronavirus disease can cause severe acute respiratory syndrome, cardiovascular and neurologic disease and a variety of serious medical sequelae; however, it is too simplistic to focus our attention on only the medical aspects and consequences of this disease. COVID-19 is extremely pervasive and definitely affects the overall health of individuals with a strong negative impact on quality of life [3], [4]. According to the latest data from the World Health Organization, as of February 1, 2021, over 102 million people have been infected with more than 2,220,000 deaths reported [5], and presently most countries are going to get a third or fourth wave of COVID-19 despite the implementation of containment measures (e.g., social distancing, restricting the movement, quarantine, etc.) which aim to reduce the spread [6], [7]. Most strict containment measures have commuted significantly people’s ways of working, studying, living, and their relationships with family and friends [8]. A major consequence of the pandemic is that many people have faced serious mental health challenges [9], [10], [11]. Several epidemiologic studies, as reported in a recent meta-analysis by Wu and colleagues [12], have shown that beyond virus pandemics, there is a “hidden pandemic” that is affecting the world population and will possibly last longer than the infective one: this is the mental health pandemic [13].

The types and severity of mental health problems may vary by age, sex, level of functioning, social roles, and pre-existing health and mental conditions [14], [15]. A recent poll conducted by the United Nations International Children's Emergency Fund (UNICEF) showed that the COVID-19 pandemic is having a significant impact on the mental health of adolescents and young people [16] and several other researchers have described the magnitude of this impact due to COVID-19 restrictions [17], [18]. Similarly, adults and elderly people have shown a decrease in their mental well-being [19], [20]. It is difficult to identify those who suffer most from the consequences of the COVID-19 pandemic; however, it is clear that the worldwide COVID-19 pandemic has imposed a huge mental health burden on the entire society [12]. A majority of the population manages to resist stress, and even build up resilience when faced with changes and difficulties; however, such a chronic, overwhelming, and life-changing event seems to be beyond the expected stressors affecting the course of individual life.

Stress responsiveness is one of the most important tools that allow our brain and body to adapt to changes and face threatening events, activating several systems including the hypothalamic–pituitaryadrenal and sympathoadrenal axes however, when a stressor is strong, prolonged, and uncertain, the stress becomes distress and has a negative effect on our somatic and mental health [21].

This overwhelming and prolonged stressor, the COVID-19 pandemic facilitates the emergence of mental disorder-vulnerabilities and the worsening of mental disorders in previously afflicted individuals. Each person, however, is, of course, unique, and personal vulnerabilities and strengths vary [15], [22].

Individuals with a past personal history of mental illness, and their families, are particularly suffering from the consequences of the pandemic: this is due to a myriad of factors including an increased risk of relapse, worsening of symptoms severity, non-adherence to medications, amplified stigma, and poor self-care with a corresponding increase in suicidal ideation and suicide attempts [23]. The pandemic and its consequences are also potential risk factors associated with new-onset psychiatric disorders that have also shown an increase in prevalence globally [24], [25]. Moreover, persons with mental health disorders have a significantly higher risk of COVID-19 with poorer outcomes [22]. Particularly, patients with bipolar disorder or schizophrenia are disproportionally affected by the consequences of the pandemic with a reduction to access and utilization of mental health services and secondary to the intrinsic core symptoms of these disorders that require considerable attention and adherence, of correct therapeutic strategies. Moreover, patients with these disorders often exhibit exacerbations of symptoms due to the lockdowns and social isolation [26], [27]. Further, patients with obsessive–compulsive disorder, especially with predominant obsessions of contamination with dirt and disease and compulsive hand washing, patients with an eating disorder [28] and those with substance use disorder [29], can also differentially suffer from the negative effects of the pandemic [30], [31]. The reaction of a patient with anxiety disorders will likely vary greatly based on the “type” of disorder and the context of the person: patients with agoraphobia might feel particularly good during lockdown especially if they are in a family setting, patients with social phobia will be relieved with social distancing, while patients with generalized anxiety disorders might worsen given the intense sense of uncertainty that is present in the pandemic days and patients with health anxiety might feel in danger and be concerned of impending doom[32].

This pandemic era is unprecedented in our epoch and requires an unparalleled response in every aspect of daily life. One of the main problems with the current pandemic is its quite long duration and uncertain end. All these aspects, combined with the lack of organization, healthcare workers, and low state investment in health, particularly for mental health care, render the current situation potentially more disturbing and complicated [4], [9], [10]. Human history has taught us that crises can offer unexpected benefits for humanity. Change, innovation, and courage are the 'ingredients' for growing out of the current crisis. In the field of mental health, preparation to overcome social and mental crises due to the consequences of the coronavirus pandemic requires changes in “business as usual”. All mental health workers should be aware of the increase in mental health disorders that will need to be addressed in the near future and we all believe that to avert a future irreversible mental health crisis, a major change of direction is urgently required. The current health system cannot sufficiently cope with an event of this magnitude [33], [34], [35], [36]. A possible solution and a way to prevent more future serious consequences relies on the implementation of the personalized medicine paradigm in mental health [37], [38]. A change of perspective has become necessary in order to advance a new medical model: focused on the individual and holding seriously into consideration his/her uniqueness, complexity, and human variability. This model is also comprised of several recent scientific and technological discoveries [37], [39], [40]. The idea of a new medical pathway toward personalization (“personalized medicine”), started at the end of the 20th century when scientists began the human genome project research (1990–2003) and, although many years have passed, a substantial change in diagnosis, prognostication, and therapeutic strategy in psychiatry has not yet occurred [41] and not reached the similar results to those obtained in other fields, such as oncology [42]. Sometimes, new inventions and scientific discoveries have led to the loss of considering the his/her entirety; we do not need to consider only the genetic and molecular profile of the patient but also personality, beliefs, values, dreams, and resources including the new concept of an “ecotype” [37], [39], [43].

This is the only way to fully understand the way a person adapts to illnesses and, concurrently, influence the type of response to different potential treatments. Moreover, patients’ families, friends, and social circles must not be forgotten [44] and must be considered a key element in a personalized approach to improving outcomes [45].

In recent years, new attempts have been proposed aiming to implement the personalized approach in the treatment of mental disorders. Personalized medicine in psychiatry may be very useful and effective as initially proposed in many theoretical papers and proof-of-concept studies. What is missing is the definite applicability to clinical practice that is still limited [46], [47].

A striking example is the wide availability of several combinatorial pharmacogenetic tests to support drug selection in psychiatric patients; however, the actual clinical utility and cost-effectiveness of this strategy is still very much in doubt. Indeed, one of the largest randomized clinical trial of pharmacogenomics to predict antidepressant efficacy, the Genomics Used to Improve Depression Decisions (GUIDED) trial, failed to meet its primary efficacy outcome measures and also failed to predict side effect liability [48] At best currently available pharmacogenetics-based tools may be helpful, in a small number of patients, only in predicting side effects and not in the choice of the most efficacious treatment in clinical practice, though this is far from clear [47], [49], [50], [51].

Another burgeoning area of research is the utilization of increasingly more available large medical data collections (“big data”) that could be capitalized on to make reliable individualized predictions in personalized medicine in psychiatry through the use of recent technological advances including forms of artificial intelligence [52], [53]. An example of this is the application of bioinformatics tools to permit the correct classification of the current mood state and the outcome of hospitalized patients with major depressive disorder in the UK [54]. Another is the application of innovative computational methods such as machine learning to derive predictive models using multimodal individual variables [39], [46], [55], [56], [57] as, for example, in a study that used clinical data previously collected in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) and Combining Medications to Enhance Depression Outcomes (CO-MED) studies. Such models aim to significantly predict clinical remission to an antidepressant in a patient with major depressive disorder [58], [59].

We would be remiss if we did not describe the clear bidirectional relationship of COVID-19 infection and psychiatric disorders. There is now robust evidence that psychiatric patients, particularly those with serious mental illness, are unusually susceptible to COVID-19 infection, morbidity, and mortality. There is, moreover, a growing appreciation of the psychiatric consequences of COVID-19 infection including new-onset psychiatric diagnoses including post-traumatic stress disorder (PTSD) [60], [61].In addition, the so-called COVID-19 “long haulers”, patients with long term medical and psychiatric sequelae after recovery from acute COVID-19 infection will clearly be a sizeable clinical population to be reckoned with in the months and years ahead.

Randomized controlled trials seeking to determine what treatments, psychopharmacological and/or psychotherapeutic, might be effective in this population are of paramount importance.

Lastly, a recent study [62] of more than 7000 patients hospitalized with COVID-19 in Paris reported markedly reduced rates of mortality, severe morbidity, intubation and intensive care unit stays and overall length of hospitalization among those admitted who were already receiving selective serotonin reuptake inhibitors (SSRIs). This raises the possibility that SSRIs may possess anti-viral activity which has recently been demonstrated [63].

This pandemic has unquestionably changed the world as we know it. The initial idea of starting a Copernican revolution, thanks to the introduction of personalized psychiatry, with indications based on scientific data integrated with the particular aspects of the patient, had created great expectations of finally changing the course and outcome of mental illness; however, the results have thus far been unsatisfactory [37].

In 2020, with the spread of COVID-19, this revolution in psychiatry has slowed down. Therefore, it is urgent to resume and galvanize world attention on the mental health crisis. With this goal in mind, we asked several expert authors to contribute their views according to their individual specialty in psychiatry, on the state of mental health during and after the COVID-19 era.

The present special issue aims to provide a starting point for discussion surrounding key questions and future challenges regarding the main mental health diseases based on our current world situation. Virtually all mental health workers are aware of the increase in psychiatric disease morbidity that will need to be addressed in the near future and believe that a major change of direction is urgently required, to avert a future irreversible mental health crisis. From the appearance of Coronavirus-phobia to the psychological issues surrounding the COVID-19 vaccine, changes in inpatient psychiatric care (and visitor policy), the change in the manner of delivering psychotherapy during the social distancing time and so much more need a broader discussion. Personalized medicine in psychiatry must play a role in this call to action.